Medicinal Plants in Cancer Treatment: Contribution of Nuclear Factor-
Kappa B (NF-kB) Inhibitors

Rina      Das; Dinesh   Kumar   Mehta; Meenakshi      Dhanawat
doi:10.2174/1389557522666220307170126
Abstract

Nuclear factor-kappa B (NF-κB) is one of the principal inducible proteins and a predominant transcription factor that is known to control gene expression in mammals. It plays a pivotal role in regulating cell signalling in the body under certain physiological and pathological conditions. In cancer cells, such as colon, breast, pancreatic, ovarian, melanoma, and lymphoma, the NF-κB pathway is active. In cellular proliferation, promoting angiogenesis, invasion, metastasis of tumour cells, and blocking apoptosis, the constitutive activity of NF-κB signalling has been reported. Therefore, immense attention has been given to developing drugs targeting NF-κB signalling pathways to treat many types of tumours. They are a desirable therapeutic target for drugs, and many studies have concentrated on recognizing compounds. They may be able to reverse or standstill the growth and spread of tumours that selectively interfere with this pathway. Recently, numerous substances derived from plants have been evaluated as possible inhibitors of the NF-κB pathway. These include various compounds, such as flavonoids, lignans, diterpenes, sesquiterpenes, polyphenols, etc. A study supported by folk medicine demonstrated that plant-derived compounds could suppress NF-κB signalling. Considering this, the present review revealed the anticancer potential of naturally occurring compounds that inhibit the NF-κB signalling and suppress the growth and spread of cancer.
Keywords: Nuclear factor-kappa B (NF-κB), NF-κB inhibitors, NF-κB signalling, NF-κB signalling pathways, natural products, cancer.
« Previous Next »
Graphical Abstract

[1] 
Baeuerle, P.A.; Baichwal, V.R. NF-kappa B as a frequent target for immunosuppressive and anti-inflammatory molecules. Adv. Immunol.,  1997, 65, 111-137.
[http://dx.doi.org/10.1016/S0065-2776(08)60742-7] [PMID: 9238509] 
[2] 
Zhang, L.; Ding, Y.; Yuan, Z.; Liu, J.; Sun, J.; Lei, F.; Wu, S.; Li, S.; Zhang, D. MicroRNA-500 sustains nuclear factor-κB activation and induces gastric cancer cell proliferation and resistance to apoptosis. Oncotarget,  2015, 6(4), 2483-2495.
[http://dx.doi.org/10.18632/oncotarget.2800] [PMID: 25595906] 
[3] 
Baldwin, A.S., Jr The NF-kappa B and I kappa B proteins: New discoveries and insights. Annu. Rev. Immunol.,  1996, 14, 649-683.
[http://dx.doi.org/10.1146/annurev.immunol.14.1.649] [PMID: 8717528] 
[4] 
Amiri, K.I.; Richmond, A. Role of nuclear factor-kappa B in melanoma. Cancer Metastasis Rev.,  2005, 24(2), 301-313.
[http://dx.doi.org/10.1007/s10555-005-1579-7] [PMID: 15986139] 
[5] 
Schön, M.; Wienrich, B.G.; Kneitz, S.; Sennefelder, H.; Amschler, K.; Vöhringer, V.; Weber, O.; Stiewe, T.; Ziegelbauer, K.; Schön, M.P. KINK-1, a novel small-molecule inhibitor of IKKbeta, and the susceptibility of melanoma cells to antitumoral treatment. J. Natl. Cancer Inst.,  2008, 100(12), 862-875.
[http://dx.doi.org/10.1093/jnci/djn174] [PMID: 18544741] 
[6] 
Nam, N.H.; Naturally Occurring, N.F-B. Naturally occurring NF-kappaB inhibitors. Mini Rev. Med. Chem.,  2006, 6(8), 945-951.
[http://dx.doi.org/10.2174/138955706777934937] [PMID: 16918500] 
[7] 
Tickle, C. Worlds in common through NF-kappaB. Nature,  1998, 392(6676), 547-549.
[http://dx.doi.org/10.1038/33276] [PMID: 9560146] 
[8] 
Sugimoto, H.; Kataoka, T.; Igarashi, M.; Hamada, M.; Takeuchi, T.; Nagai, K. E-73, an acetoxyl analogue of cycloheximide, blocks the tumor necrosis factor-induced NF-kappaB signaling pathway. Biochem. Biophys. Res. Commun.,  2000, 277(2), 330-333.
[http://dx.doi.org/10.1006/bbrc.2000.3680] [PMID: 11032726] 
[9] 
Meng, C.; Zhu, H.; Song, H.; Wang, Z.; Huang, G.; Li, D.; Ma, Z.; Ma, J.; Qin, Q.; Sun, X.; Ma, J. Targets and molecular mechanisms of triptolide in cancer therapy. Chin. J. Cancer Res.,  2014, 26(5), 622-626.
[PMID: 25400429] 
[10] 
Ghosh, S.; May, M.J.; Kopp, E.B. NF-kappa B and Rel proteins: Evolutionarily conserved mediators of immune responses. Annu. Rev. Immunol.,  1998, 16, 225-260.
[http://dx.doi.org/10.1146/annurev.immunol.16.1.225] [PMID: 9597130] 
[11] 
Pahl, H.L. Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene,  1999, 18(49), 6853-6866.
[http://dx.doi.org/10.1038/sj.onc.1203239] [PMID: 10602461] 
[12] 
Bastian, H.; Johannes, A.S. The complexity of NF-kB signalling in inflammation and cancer. Mol. Cancer,  2013, 12, 1-15.
[13] 
Bonizzi, G.; Karin, M. The two NF-kappaB activation pathways and their role in innate and adaptive immunity. Trends Immunol.,  2004, 25(6), 280-288.
[http://dx.doi.org/10.1016/j.it.2004.03.008] [PMID: 15145317] 
[14] 
Hayden, M.S.; Ghosh, S. Signaling to NF-kappaB. Genes Dev.,  2004, 18(18), 2195-2224.
[http://dx.doi.org/10.1101/gad.1228704] [PMID: 15371334] 
[15] 
Häcker, H.; Karin, M. Regulation and function of IKK and IKK-related kinases. Sci. STKE,  2006, 2006(357), 3.
[http://dx.doi.org/10.1126/stke.3572006re13] [PMID: 17047224] 
[16] 
Tew, G.W.; Lorimer, E.L.; Berg, T.J.; Zhi, H.; Li, R.; Williams, C.L. SmgGDS regulates cell proliferation, migration, and NF-kappaB transcriptional activity in non-small cell lung carcinoma. J. Biol. Chem.,  2008, 283(2), 963-976.
[http://dx.doi.org/10.1074/jbc.M707526200] [PMID: 17951244] 
[17] 
Chua, H.L.; Bhat-Nakshatri, P.; Clare, S.E.; Morimiya, A.; Badve, S.; Nakshatri, H. NF-kappaB represses E-cadherin expression and enhances epithelial to mesenchymal transition of mammary epithelial cells: Potential involvement of ZEB-1 and ZEB-2. Oncogene,  2007, 26(5), 711-724.
[http://dx.doi.org/10.1038/sj.onc.1209808] [PMID: 16862183] 
[18] 
Zou, P.; Kawada, J.; Pesnicak, L.; Cohen, J.I. Bortezomib induces apoptosis of Epstein-Barr virus (EBV)-transformed B cells and prolongs survival of mice inoculated with EBV-transformed B cells. J. Virol.,  2007, 81(18), 10029-10036.
[http://dx.doi.org/10.1128/JVI.02241-06] [PMID: 17626072] 
[19] 
Vilimas, T.; Mascarenhas, J.; Palomero, T.; Mandal, M.; Buonamici, S.; Meng, F.; Thompson, B.; Spaulding, C.; Macaroun, S.; Alegre, M.L.; Kee, B.L.; Ferrando, A.; Miele, L.; Aifantis, I. Targeting the NF-kappaB signaling pathway in Notch1-induced T-cell leukemia. Nat. Med.,  2007, 13(1), 70-77.
[http://dx.doi.org/10.1038/nm1524] [PMID: 17173050] 
[20] 
Annunziata, C.M.; Stavnes, H.T.; Kleinberg, L.; Berner, A.; Hernandez, L.F.; Birrer, M.J.; Steinberg, S.M.; Davidson, B.; Kohn, E.C. Nuclear factor kappaB transcription factors are coexpressed and convey a poor outcome in ovarian cancer. Cancer,  2010, 116(13), 3276-3284.
[http://dx.doi.org/10.1002/cncr.25190] [PMID: 20564628] 
[21] 
Brown, R.E.; Law, A. Morphoproteomic demonstration of constitutive nuclear factor-kappaB activation in glioblastoma multiforme with genomic correlates and therapeutic implications. Ann. Clin. Lab. Sci.,  2006, 36(4), 421-426.
[PMID: 17127728] 
[22] 
Li, Y.; Ahmed, F.; Ali, S.; Philip, P.A.; Kucuk, O.; Sarkar, F.H. Inactivation of nuclear factor kappaB by soy isoflavone genistein contributes to increased apoptosis induced by chemotherapeutic agents in human cancer cells. Cancer Res.,  2005, 65(15), 6934-6942.
[http://dx.doi.org/10.1158/0008-5472.CAN-04-4604] [PMID: 16061678] 
[23] 
Richardson, P.G.; Mitsiades, C.; Hideshima, T.; Anderson, K.C. Bortezomib: Proteasome inhibition as an effective anticancer therapy. Annu. Rev. Med.,  2006, 57, 33-47.
[http://dx.doi.org/10.1146/annurev.med.57.042905.122625] [PMID: 16409135] 
[24] 
Schreck, R.; Meier, B.; Männel, D.N.; Dröge, W.; Baeuerle, P.A. Dithiocarbamates as potent inhibitors of nuclear factor kappa B activation in intact cells. J. Exp. Med.,  1992, 175(5), 1181-1194.
[http://dx.doi.org/10.1084/jem.175.5.1181] [PMID: 1314883] 
[25] 
D’Acquisto, F.; Ialenti, A.; Ianaro, A.; Di Vaio, R.; Carnuccio, R. Local administration of transcription factor decoy oligonucleotides to nuclear factor-kappaB prevents carrageenin-induced inflammation in rat hind paw. Gene Ther.,  2000, 7(20), 1731-1737.
[http://dx.doi.org/10.1038/sj.gt.3301295] [PMID: 11083494] 
[26] 
McKay, L.I.; Cidlowski, J.A. Cross-talk between nuclear factor-kappa B and the steroid hormone receptors: Mechanisms of mutual antagonism. Mol. Endocrinol.,  1998, 12(1), 45-56.
[http://dx.doi.org/10.1210/mend.12.1.0044] [PMID: 9440809] 
[27] 
Higgins, K.A.; Perez, J.R.; Coleman, T.A.; Dorshkind, K.; McComas, W.A.; Sarmiento, U.M.; Rosen, C.A.; Narayanan, R. Antisense inhibition of the p65 subunit of NF-kappa B blocks tumorigenicity and causes tumor regression. Proc. Natl. Acad. Sci. USA,  1993, 90(21), 9901-9905.
[http://dx.doi.org/10.1073/pnas.90.21.9901] [PMID: 8234333] 
[28] 
Ghosh, S.; Karin, M. Missing pieces in the NF-kappaB puzzle. Cell,  2002, 109(Suppl.), S81-S96.
[http://dx.doi.org/10.1016/S0092-8674(02)00703-1] [PMID: 11983155] 
[29] 
Avci, N.G.; Ebrahimzadeh-Pustchi, S.; Akay, Y.M.; Esquenazi, Y.; Tandon, N.; Zhu, J.J.; Akay, M. 
                        NF-κB inhibitor with Temozolomide results in significant apoptosis in glioblastoma 
                        via
                         the NF-κB(p65) and actin cytoskeleton regulatory pathways.
                     Sci. Rep.,  2020, 10(1), 13352.
[http://dx.doi.org/10.1038/s41598-020-70392-5] [PMID: 32770097] 
[30] 
Inglés-Esteve, J.; Morales, M.; Dalmases, A.; Garcia-Carbonell, R.; Jené-Sanz, A.; López-Bigas, N.; Iglesias, M.; Ruiz-Herguido, C.; Rovira, A.; Rojo, F.; Albanell, J.; Gomis, R.R.; Bigas, A.; Espinosa, L. Inhibition of specific NF-κB activity contributes to the tumor suppressor function of 14-3-3σ in breast cancer. PLoS One,  2012, 7(5), e38347.
[http://dx.doi.org/10.1371/journal.pone.0038347] [PMID: 22675457] 
[31] 
Rasmi, R.R.; Sakthivel, K.M.; Guruvayoorappan, C. NF-κB inhibitors in treatment and prevention of lung cancer. Biomed. Pharmacother.,  2020, 130, 110569.
[http://dx.doi.org/10.1016/j.biopha.2020.110569] [PMID: 32750649] 
[32] 
Chao, W.; Deng, J.S.; Li, P.Y.; Liang, Y.C.; Huang, G.J. 
                        3,4-Dihydroxybenzalactone suppresses human non-small cell lung carcinoma cells metastasis 
                        via
                         suppression of epithelial to mesenchymal transition, ROS-mediated PI3K/AKT/MAPK/MMP and NFκB signalling pathways.
                     Molecules,  2017, 22(4), 537-551.
[http://dx.doi.org/10.3390/molecules22040537] [PMID: 28350337] 
[33] 
Basu, P.; Maier, C. 
                        Phytoestrogens and breast cancer: 
                        In vitro
                         anticancer activities of isoflavones, lignans, coumestans, stilbenes and their analogs and derivatives.
                     Biomed. Pharmacother.,  2018, 107, 1648-1666.
[http://dx.doi.org/10.1016/j.biopha.2018.08.100] [PMID: 30257383] 
[34] 
Natarajan, K.; Singh, S.; Burke, T.R., Jr; Grunberger, D.; Aggarwal, B.B. Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-kappa B. Proc. Natl. Acad. Sci. USA,  1996, 93(17), 9090-9095.
[http://dx.doi.org/10.1073/pnas.93.17.9090] [PMID: 8799159] 
[35] 
Bharti, A.C.; Aggarwal, B.B. Nuclear factor-kappa B and cancer: Its role in prevention and therapy. Biochem. Pharmacol.,  2002, 64(5-6), 883-888.
[http://dx.doi.org/10.1016/S0006-2952(02)01154-1] [PMID: 12213582] 
[36] 
Carrasco-Legleu, C.E.; Márquez-Rosado, L.; Fattel-Fazenda, S.; Arce-Popoca, E.; Pérez-Carreón, J.I.; Villa-Treviño, S. Chemoprotective effect of caffeic acid phenethyl ester on promotion in a medium-term rat hepatocarcinogenesis assay. Int. J. Cancer,  2004, 108(4), 488-492.
[http://dx.doi.org/10.1002/ijc.11595] [PMID: 14696111] 
[37] 
Huang, M.T.; Ma, W.; Yen, P.; Xie, J.G.; Han, J.; Frenkel, K.; Grunberger, D.; Conney, A.H. Inhibitory effects of caffeic acid phenethyl ester (CAPE) on 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion in mouse skin and the synthesis of DNA, RNA and protein in HeLa cells. Carcinogenesis,  1996, 17(4), 761-765.
[http://dx.doi.org/10.1093/carcin/17.4.761] [PMID: 8625488] 
[38] 
Beltrán-Ramírez, O.; Pérez, R.M.; Sierra-Santoyo, A.; Villa-Treviño, S. Cancer prevention mediated by caffeic acid phenethyl ester involves cyp2b1/2 modulation in hepatocarcinogenesis. Toxicol. Pathol.,  2012, 40(3), 466-472.
[http://dx.doi.org/10.1177/0192623311431947] [PMID: 22291063] 
[39] 
Maffia, P.; Ianaro, A.; Pisano, B.; Borrelli, F.; Capasso, F.; Pinto, A.; Ialenti, A. Beneficial effects of caffeic acid phenethyl ester in a rat model of vascular injury. Br. J. Pharmacol.,  2002, 136(3), 353-360.
[http://dx.doi.org/10.1038/sj.bjp.0704720] [PMID: 12023937] 
[40] 
Burdock, G.A. Review of the biological properties and toxicity of bee propolis (propolis). Food Chem. Toxicol.,  1998, 36(4), 347-363.
[http://dx.doi.org/10.1016/S0278-6915(97)00145-2] [PMID: 9651052] 
[41] 
Komericki, P.; Kränke, B. Maculopapular exanthem from propolis: Case report and review of systemic cutaneous and non-cutaneous reactions. Contact Dermat.,  2009, 61(6), 353-355.
[http://dx.doi.org/10.1111/j.1600-0536.2009.01642.x] [PMID: 20059499] 
[42] 
Kizilay, A.; Kalcioglu, M.T.; Ozerol, E.; Iraz, M.; Gulec, M.; Akyol, O.; Ozturan, O. Caffeic acid phenethyl ester ameliorated ototoxicity induced by cisplatin in rats. J. Chemother.,  2004, 16(4), 381-387.
[http://dx.doi.org/10.1179/joc.2004.16.4.381] [PMID: 15332714] 
[43] 
Chen, Y-J.; Liao, H-F.; Tsai, T-H.; Wang, S-Y.; Shiao, M-S. Caffeic acid phenethyl ester preferentially sensitizes CT26 colorectal adenocarcinoma to ionizing radiation without affecting bone marrow radioresponse. Int. J. Radiat. Oncol. Biol. Phys.,  2005, 63(4), 1252-1261.
[http://dx.doi.org/10.1016/j.ijrobp.2005.08.001] [PMID: 16253780] 
[44] 
Yang, C.S.; Maliakal, P.; Meng, X. Inhibition of carcinogenesis by tea. Annu. Rev. Pharmacol. Toxicol.,  2002, 42, 25-54.
[http://dx.doi.org/10.1146/annurev.pharmtox.42.082101.154309] [PMID: 11807163] 
[45] 
Khan, N.; Adhami, V.M.; Mukhtar, H. Review: Green tea polyphenols in chemoprevention of prostate cancer: Preclinical and clinical studies. Nutr. Cancer,  2009, 61(6), 836-841.
[http://dx.doi.org/10.1080/01635580903285056] [PMID: 20155624] 
[46] 
Bettuzzi, S.; Brausi, M.; Rizzi, F.; Castagnetti, G.; Peracchia, G.; Corti, A. Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: A preliminary report from a one-year proof-of-principle study. Cancer Res.,  2006, 66(2), 1234-1240.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-1145] [PMID: 16424063] 
[47] 
Brausi, M.; Rizzi, F.; Bettuzzi, S. Chemoprevention of human prostate cancer by green tea catechins: Two years later. A follow-up update. Eur. Urol.,  2008, 54(2), 472-473.
[http://dx.doi.org/10.1016/j.eururo.2008.03.100] [PMID: 18406041] 
[48] 
Suhail, M.; Parveen, A.; Husain, A.; Rehan, M. Exploring inhibitory mechanisms of green tea catechins as inhibitors of a cancer therapeutic target, nuclear factor-κB (NF-κB). Biosci. Biotechnol. Res. Asia,  2019, 16, 715-723.
[http://dx.doi.org/10.13005/bbra/2787] 
[49] 
Siddiqui, I.A.; Shukla, Y.; Adhami, V.M.; Sarfaraz, S.; Asim, M.; Hafeez, B.B.; Mukhtar, H. Suppression of NFkappaB and its regulated gene products by oral administration of green tea polyphenols in an autochthonous mouse prostate cancer model. Pharm. Res.,  2008, 25(9), 2135-2142.
[http://dx.doi.org/10.1007/s11095-008-9553-z] [PMID: 18317887] 
[50] 
Yang, F.; Oz, H.S.; Barve, S.; de Villiers, W.J.; McClain, C.J.; Varilek, G.W. The green tea polyphenol (-)-epigallocatechin-3- gallate blocks nuclear factor-kappa B activation by inhibiting I kappa B kinase activity in the intestinal epithelial cell line IEC-6. Mol. Pharmacol.,  2001, 60(3), 528-533.
[PMID: 11502884] 
[51] 
Chen, L.; Zhang, H.Y. Cancer preventive mechanisms of the green tea polyphenol (-)-epigallocatechin-3-gallate. Molecules,  2007, 12(5), 946-957.
[http://dx.doi.org/10.3390/12050946] [PMID: 17873830] 
[52] 
Singh, M.; Singh, R.; Bhui, K.; Tyagi, S.; Mahmood, Z.; Shukla, Y. Tea polyphenols induce apoptosis through mitochondrial pathway and by inhibiting nuclear factor-kappaB and Akt activation in human cervical cancer cells. Oncol. Res.,  2011, 19(6), 245-257.
[http://dx.doi.org/10.3727/096504011X13021877989711] [PMID: 21776820] 
[53] 
Qin, J.; Wang, Y.; Bai, Y.; Yang, K.; Mao, Q.; Lin, Y.; Kong, D.; Zheng, X.; Xie, L. 
                        Epigallocatechin-3-gallate inhibits bladder cancer cell invasion 
                        via
                         suppression of NF-κB-mediated matrix metalloproteinase-9 expression.
                     Mol. Med. Rep.,  2012, 6(5), 1040-1044.
[http://dx.doi.org/10.3892/mmr.2012.1054] [PMID: 22941057] 
[54] 
Pianetti, S.; Guo, S.; Kavanagh, K.T.; Sonenshein, G.E. Green tea polyphenol epigallocatechin-3 gallate inhibits Her-2/Neu signalling, proliferation, and transformed phenotype of breast cancer cells. Cancer Res.,  2002, 652-655.
[55] 
Zhang, L.; Xie, J.; Gan, R.; Wu, Z.; Luo, H.; Chen, X.; Lu, Y.; Wu, L.; Zheng, D. Synergistic inhibition of lung cancer cells by EGCG and NF-κB inhibitor BAY11-7082. J. Cancer,  2019, 10(26), 6543-6556.
[http://dx.doi.org/10.7150/jca.34285] [PMID: 31777584] 
[56] 
Harikumar, K.B.; Kunnumakkara, A.B.; Sethi, G.; Diagaradjane, P.; Anand, P.; Pandey, M.K.; Gelovani, J.; Krishnan, S.; Guha, S.; Aggarwal, B.B. Resveratrol, a multitargeted agent, can enhance antitumor activity of gemcitabine in vitro and in orthotopic mouse model of human pancreatic cancer. Int. J. Cancer,  2010, 127(2), 257-268.
[PMID: 19908231] 
[57] 
Bhat, K.P.; Pezzuto, J.M. Cancer chemopreventive activity of resveratrol. Ann. N. Y. Acad. Sci.,  2002, 957, 210-229.
[http://dx.doi.org/10.1111/j.1749-6632.2002.tb02918.x] [PMID: 12074974] 
[58] 
Alkhalaf, M.; Jaffal, S. Potent antiproliferative effects of resveratrol on human osteosarcoma SJSA1 cells: Novel cellular mechanisms involving the ERKs/p53 cascade. Free Radic. Biol. Med.,  2006, 41(2), 318-325.
[http://dx.doi.org/10.1016/j.freeradbiomed.2006.04.019] [PMID: 16814113] 
[59] 
Kumar, R.; Srinivasan, S.; Koduru, S.; Pahari, P.; Rohr, J.; Kyprianou, N.; Damodaran, C. Psoralidin, an herbal molecule, inhibits phosphatidylinositol 3-kinase–mediated Akt signalling in androgen-independent prostate cancer cells. Cancer Prev. Res. (Phila.),  2009, 2(3), 234-243.
[http://dx.doi.org/10.1158/1940-6207.CAPR-08-0129] [PMID: 19223576] 
[60] 
Wang, Z.; Zhang, Y.; Banerjee, S.; Li, Y.; Sarkar, F.H. Notch-1 down-regulation by curcumin is associated with the inhibition of cell growth and the induction of apoptosis in pancreatic cancer cells. Cancer,  2006, 106(11), 2503-2513.
[http://dx.doi.org/10.1002/cncr.21904] [PMID: 16628653] 
[61] 
Carroll, R.E.; Benya, R.V.; Turgeon, D.K.; Vareed, S.; Neuman, M.; Rodriguez, L.; Kakarala, M.; Carpenter, P.M.; McLaren, C.; Meyskens, F.L., Jr; Brenner, D.E. Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer Prev. Res. (Phila.),  2011, 4(3), 354-364.
[http://dx.doi.org/10.1158/1940-6207.CAPR-10-0098] [PMID: 21372035] 
[62] 
Kumar, A.; Dhawan, S.; Hardegen, N.J.; Aggarwal, B.B. Curcumin (Diferuloylmethane) inhibition of Tumor Necrosis Factor (TNF)-mediated adhesion of monocytes to endothelial cells by suppression of cell surface expression of adhesion molecules and of nuclear factor-kappaB activation. Biochem. Pharmacol.,  1998, 55(6), 775-783.
[http://dx.doi.org/10.1016/S0006-2952(97)00557-1] [PMID: 9586949] 
[63] 
Reuter, S.; Eifes, S.; Dicato, M.; Aggarwal, B.B.; Diederich, M. Modulation of anti-apoptotic and survival pathways by curcumin as a strategy to induce apoptosis in cancer cells. Biochem. Pharmacol.,  2008, 76(11), 1340-1351.
[http://dx.doi.org/10.1016/j.bcp.2008.07.031] [PMID: 18755156] 
[64] 
Odot, J.; Albert, P.; Carlier, A.; Tarpin, M.; Devy, J.; Madoulet, C. 
                            In vitro
                        
                         and 
                        in vivo
                         anti-tumoral effect of curcumin against melanoma cells.
                     Int. J. Cancer,  2004, 111(3), 381-387.
[http://dx.doi.org/10.1002/ijc.20160] [PMID: 15221965] 
[65] 
Dhillon, N.; Aggarwal, B.B.; Newman, R.A.; Wolff, R.A.; Kunnumakkara, A.B.; Abbruzzese, J.L.; Ng, C.S.; Badmaev, V.; Kurzrock, R. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin. Cancer Res.,  2008, 14(14), 4491-4499.
[http://dx.doi.org/10.1158/1078-0432.CCR-08-0024] [PMID: 18628464] 
[66] 
Tsai, S.H.; Liang, Y.C.; Lin-Shiau, S.Y.; Lin, J.K. Suppression of TNFalpha-mediated NFkappaB activity by myricetin and other flavonoids through downregulating the activity of IKK in ECV304 cells. J. Cell. Biochem.,  1999, 74(4), 606-615.
[http://dx.doi.org/10.1002/(SICI)1097-4644(19990915)74:4<606:AID-JCB10>3.0.CO;2-W] [PMID: 10440930] 
[67] 
Gupta, S.; Afaq, F.; Mukhtar, H. Involvement of nuclear factor-kappa B, Bax and Bcl-2 in induction of cell cycle arrest and apoptosis by apigenin in human prostate carcinoma cells. Oncogene,  2002, 21(23), 3727-3738.
[http://dx.doi.org/10.1038/sj.onc.1205474] [PMID: 12032841] 
[68] 
Shukla, S.; Gupta, S. Suppression of constitutive and tumor necrosis factor alpha-induced nuclear factor (NF)-kappaB activation and induction of apoptosis by apigenin in human prostate carcinoma PC-3 cells: Correlation with down-regulation of NF-kappaB-responsive genes. Clin. Cancer Res.,  2004, 10(9), 3169-3178.
[http://dx.doi.org/10.1158/1078-0432.CCR-03-0586] [PMID: 15131058] 
[69] 
Shukla, S.; Shankar, E.; Fu, P.; MacLennan, G.T.; Gupta, S. Suppression of NF-κB and NF-κB-regulated gene expression by apigenin through IκBα and IKK pathway in TRAMP mice. PLoS One,  2015, 10(9), e0138710.
[http://dx.doi.org/10.1371/journal.pone.0138710] [PMID: 26379052] 
[70] 
Shukla, S.; Kanwal, R.; Shankar, E.; Datt, M.; Chance, M.R.; Fu, P.; MacLennan, G.T.; Gupta, S. Apigenin blocks IKKα activation and suppresses prostate cancer progression. Oncotarget,  2015, 6(31), 31216-31232.
[http://dx.doi.org/10.18632/oncotarget.5157] [PMID: 26435478] 
[71] 
Seo, H.-S.; Choi, H.-S.; Kim, S.-R.; Choi, Y.K.; Woo, S.-M.; Shin, I.; Woo, J.-K.; Park, S.-Y.; Shin, Y.C.; Ko, S.-G. Apigenin induces
apoptosis via extrinsic pathway, inducing p53 and inhibiting
STAT3 and NFK B signalling in HER2-overexpressing breast cancer
cells Mol. Cell. Biochem.,  2012, 366, 319e334.
[72] 
Tong, J.; Shen, Y.; Zhang, Z.; Hu, Y.; Zhang, X.; Han, L. Apigenin inhibits epithelial-mesenchymal transition of human colon cancer cells through NF-κB/Snail signaling pathway. Biosci. Rep.,  2019, 39(5), BSR20190452.
[http://dx.doi.org/10.1042/BSR20190452] [PMID: 30967496] 
[73] 
Chen, M.; Wang, X.; Zha, D.; Cai, F.; Zhang, W.; He, Y.; Huang, Q.; Zhuang, H.; Hua, Z.C. 
                        Apigenin potentiates TRAIL therapy of non-small cell lung cancer 
                        via
                         upregulating DR4/DR5 expression in a p53-dependent manner.
                     Sci. Rep.,  2016, 6, 35468.
[http://dx.doi.org/10.1038/srep35468] [PMID: 27752089] 
[74] 
Masuelli, L.; Benvenuto, M.; Mattera, R.; Di Stefano, E.; Zago, E.; Taffera, G.; Tresoldi, I.; Giganti, M.G.; Frajese, G.V.; Berardi, G.; Modesti, A.; Bei, R. 
                            In vitro
                        
                         and 
                        in vivo
                         anti-tumoral effects of the flavonoid apigenin in malignant mesothelioma.
                     Front. Pharmacol.,  2017, 8, 373.
[http://dx.doi.org/10.3389/fphar.2017.00373] [PMID: 28674496] 
[75] 
Vargas, A.J.; Burd, R. Hormesis and synergy: Pathways and mechanisms of quercetin in cancer prevention and management. Nutr. Rev.,  2010, 68(7), 418-428.
[http://dx.doi.org/10.1111/j.1753-4887.2010.00301.x] [PMID: 20591109] 
[76] 
Nam, N-H. Naturally Occurring NF-B Inhibitors,  2006, 6(8), 945-951.
[77] 
Tanigawa, S.; Fujii, M.; Hou, D.X. Stabilization of p53 is involved in quercetin-induced cell cycle arrest and apoptosis in HepG2 cells. Biosci. Biotechnol. Biochem.,  2008, 72(3), 797-804.
[http://dx.doi.org/10.1271/bbb.70680] [PMID: 18323654] 
[78] 
Lai, W-W.; Hsu, S-C.; Chueh, F-S.; Chen, Y-Y.; Yang, J-S.; Lin, J-P.; Lien, J-C.; Tsai, C-H.; Chung, J-G. Quercetin inhibits migration and invasion of SAS human oral cancer cells through inhibition of NF-κB and matrix metalloproteinase-2/-9 signaling pathways. Anticancer Res.,  2013, 33(5), 1941-1950.
[PMID: 23645742] 
[79] 
Youn, H.S.; Jeong, J-C.; Jeong, Y.S.; Kim, E-J.; Um, S-J. Quercetin potentiates apoptosis by inhibiting nuclear factor-kappaB signalling in H460 lung cancer cells. Biol. Pharm. Bull.,  2013, 36(6), 944-951.
[http://dx.doi.org/10.1248/bpb.b12-01004] [PMID: 23727915] 
[80] 
Zhang, X-A.; Zhang, S.; Yin, Q.; Zhang, J. Quercetin induces human colon cancer cells apoptosis by inhibiting the nuclear factor-kappa B Pathway. Pharmacogn. Mag.,  2015, 11(42), 404-409.
[http://dx.doi.org/10.4103/0973-1296.153096] [PMID: 25829782] 
[81] 
Khan, F.; Niaz, K.; Maqbool, F.; Ismail Hassan, F.; Abdollahi, M.; Nagulapalli Venkata, K.C.; Nabavi, S.M.; Bishayee, A. Molecular targets underlying the anticancer effects of quercetin: an update. Nutrients,  2016, 8(9), 529-548.
[http://dx.doi.org/10.3390/nu8090529] [PMID: 27589790] 
[82] 
Ren, K.W.; Li, Y.H.; Wu, G.; Ren, J.Z.; Lu, H.B.; Li, Z.M.; Han, X.W. 
                        Quercetin nanoparticles display antitumor activity 
                        via
                         proliferation inhibition and apoptosis induction in liver cancer cells.
                     Int. J. Oncol.,  2017, 50(4), 1299-1311.
[http://dx.doi.org/10.3892/ijo.2017.3886] [PMID: 28259895] 
[83] 
Ward, A.B.; Mir, H.; Kapur, N.; Gales, D.N.; Carriere, P.P.; Singh, S. Quercetin inhibits prostate cancer by attenuating cell survival and inhibiting anti-apoptotic pathways. World J. Surg. Oncol.,  2018, 16(1), 108-115.
[http://dx.doi.org/10.1186/s12957-018-1400-z] [PMID: 29898731] 
[84] 
Li, X.; Wang, J.N.; Xiong, X. Acceleration of chrysin on apoptosis of hepatoma cell lines HepG2 induced by TNF-α. Chin. Tradit. Herbal Drugs,  2010, 41, 1828-1834.
[85] 
Park, M.H.; Hong, J.E.; Park, E.S.; Yoon, H.S.; Seo, D.W.; Hyun, B.K.; Han, S.B.; Ham, Y.W.; Hwang, B.Y.; Hong, J.T. 
                        Anticancer effect of tectochrysin in colon cancer cell 
                        via
                         suppression of NF-kappaB activity and enhancement of death receptor expression.
                     Mol. Cancer,  2015, 14, 124-136.
[http://dx.doi.org/10.1186/s12943-015-0377-2] [PMID: 26123287] 
[86] 
Khoo, B.Y.; Chua, S.L.; Balaram, P. Apoptotic effects of chrysin in human cancer cell lines. Int. J. Mol. Sci.,  2010, 11(5), 2188-2199.
[http://dx.doi.org/10.3390/ijms11052188] [PMID: 20559509] 
[87] 
Rehman, M.U.; Tahir, M.; Khan, A.Q.; Khan, R.; Lateef, A. Oday-O-Hamiza; Qamar, W.; Ali, F.; Sultana, S. Chrysin suppresses renal carcinogenesis via amelioration of hyperproliferation, oxidative stress and inflammation: Plausible role of NF-κB. Toxicol. Lett.,  2013, 216(2-3), 146-158.
[http://dx.doi.org/10.1016/j.toxlet.2012.11.013] [PMID: 23194824] 
[88] 
Xia, Y.; Lian, S.; Khoi, P.N.; Yoon, H.J.; Han, J.Y.; Chay, K.O.; Kim, K.K.; Jung, Y.D. 
                        Chrysin inhibits cell invasion by inhibition of Recepteur d’origine Nantais 
                        via
                         suppressing early growth response-1 and NF-κB transcription factor activities in gastric cancer cells.
                     Int. J. Oncol.,  2015, 46(4), 1835-1843.
[http://dx.doi.org/10.3892/ijo.2015.2847] [PMID: 25625479] 
[89] 
Oh, S.B.; Hwang, C.J.; Song, S.Y.; Jung, Y.Y.; Yun, H.M.; Sok, C.H.; Sung, H.C.; Yi, J.M.; Park, D.H.; Ham, Y.W.; Han, S.B.; Hwang, B.Y.; Hong, J.T. Anti-cancer effect of tectochrysin in NSCLC cells through overexpression of death receptor and inactivation of STAT3. Cancer Lett.,  2014, 353(1), 95-103.
[http://dx.doi.org/10.1016/j.canlet.2014.07.007] [PMID: 25083589] 
[90] 
Lin, Y.; Shi, R.; Wang, X.; Shen, H.M. Luteolin, a flavonoid with potential for cancer prevention and therapy. Curr. Cancer Drug Targets,  2008, 8(7), 634-646.
[http://dx.doi.org/10.2174/156800908786241050] [PMID: 18991571] 
[91] 
Xavier, C.P.; Lima, C.F.; Preto, A.; Seruca, R.; Fernandes-Ferreira, M.; Pereira-Wilson, C. Luteolin, quercetin and ursolic acid are potent inhibitors of proliferation and inducers of apoptosis in both KRAS and BRAF mutated human colorectal cancer cells. Cancer Lett.,  2009, 281(2), 162-170.
[http://dx.doi.org/10.1016/j.canlet.2009.02.041] [PMID: 19344998] 
[92] 
Imran, M.; Rauf, A.; Abu-Izneid, T.; Nadeem, M.; Shariati, M.A.; Khan, I.A.; Imran, A.; Orhan, I.E.; Rizwan, M.; Atif, M.; Gondal, T.A.; Mubarak, M.S. Luteolin, a flavonoid, as an anticancer agent: A review. Biomed. Pharmacother.,  2019, 112, 108612.
[http://dx.doi.org/10.1016/j.biopha.2019.108612] [PMID: 30798142] 
[93] 
Pandurangan, A.K.; Kumar, S.A.; Dharmalingam, P.; Ganapasam, S. Luteolin, a bioflavonoid inhibits azoxymethane-induced colon carcinogenesis: Involvement of iNOS and COX-2. Pharmacogn. Mag.,  2014, 10(Suppl. 2), S306-S310.
[http://dx.doi.org/10.4103/0973-1296.133285] [PMID: 24991108] 
[94] 
Bothe, H.; Götz, C.; Stobbe-Maicherski, N.; Fritsche, E.; Abel, J.; Haarmann-Stemmann, T. Luteolin enhances the bioavailability of benzo(a)pyrene in human colon carcinoma cells. Arch. Biochem. Biophys.,  2010, 498(2), 111-118.
[http://dx.doi.org/10.1016/j.abb.2010.04.009] [PMID: 20403331] 
[95] 
Johnson, J.L.; Gonzalez de Mejia, E. 
                        Interactions between dietary flavonoids apigenin or luteolin and chemotherapeutic drugs to potentiate anti-proliferative effect on human pancreatic cancer cells, 
                        in vitro
                        .
                     Food Chem. Toxicol.,  2013, 60, 83-91.
[http://dx.doi.org/10.1016/j.fct.2013.07.036] [PMID: 23871783] 
[96] 
Stathopoulos, G.T.; Sherrill, T.P.; Cheng, D.S.; Scoggins, R.M.; Han, W.; Polosukhin, V.V.; Connelly, L.; Yull, F.E.; Fingleton, B.; Blackwell, T.S. Epithelial NF-kappaB activation promotes urethane-induced lung carcinogenesis. Proc. Natl. Acad. Sci. USA,  2007, 104(47), 18514-18519.
[http://dx.doi.org/10.1073/pnas.0705316104] [PMID: 18000061] 
[97] 
Malhi, H.; Gores, G.J. TRAIL resistance results in cancer progression: A TRAIL to perdition? Oncogene,  2006, 25(56), 7333-7335.
[http://dx.doi.org/10.1038/sj.onc.1209765] [PMID: 16785986] 
[98] 
Cai, X.; Lu, W.; Ye, T.; Lu, M.; Wang, J.; Huo, J.; Qian, S.; Wang, X.; Cao, P. The molecular mechanism of luteolin-induced apoptosis is potentially related to inhibition of angiogenesis in human pancreatic carcinoma cells. Oncol. Rep.,  2012, 28(4), 1353-1361.
[http://dx.doi.org/10.3892/or.2012.1914] [PMID: 22825765] 
[99] 
Zhou, Q.; Yan, B.; Hu, X.; Li, X.B.; Zhang, J.; Fang, J. Luteolin inhibits invasion of prostate cancer PC3 cells through E-cadherin. Mol. Cancer Ther.,  2009, 8(6), 1684-1691.
[http://dx.doi.org/10.1158/1535-7163.MCT-09-0191] [PMID: 19509250] 
[100] 
Niu, J.X.; Guo, H.P.; Gan, H.M.; Bao, L.D.; Ren, J.J. Effect of luteolin on gene expression in mouse H22 hepatoma cells. Genet. Mol. Res.,  2015, 14(4), 14448-14456.
[http://dx.doi.org/10.4238/2015.November.18.7] [PMID: 26600503] 
[101] 
Huang, L.; Jin, K.; Lan, H. Luteolin inhibits cell cycle progression and induces apoptosis of breast cancer cells through downregulation of human telomerase reverse transcriptase. Oncol. Lett.,  2019, 17(4), 3842-3850.
[http://dx.doi.org/10.3892/ol.2019.10052] [PMID: 30930986] 
[102] 
Imran, M.; Saeed, F.; Gilani, S.A.; Shariati, M.A.; Imran, A.; Afzaal, M.; Atif, M.; Tufail, T.; Anjum, F.M. Fisetin: An anticancer perspective. Food Sci. Nutr.,  2020, 9(1), 3-16.
[http://dx.doi.org/10.1002/fsn3.1872] [PMID: 33473265] 
[103] 
Sung, B.; Pandey, M.K.; Aggarwal, B.B. Fisetin, an inhibitor of cyclin-dependent kinase 6, down-regulates nuclear factor-kappaB-regulated cell proliferation, antiapoptotic and metastatic gene products through the suppression of TAK-1 and receptor-interacting protein-regulated IkappaBalpha kinase activation. Mol. Pharmacol.,  2007, 71(6), 1703-1714.
[http://dx.doi.org/10.1124/mol.107.034512] [PMID: 17387141] 
[104] 
Kashyap, D.; Garg, V.K.; Tuli, H.S.; Yerer, M.B.; Sak, K.; Sharma, A.K.; Kumar, M.; Aggarwal, V.; Sandhu, S.S. Fisetin and quercetin: Promising flavonoids with chemopreventive potential. Biomolecules,  2019, 9(5), 174.
[http://dx.doi.org/10.3390/biom9050174] [PMID: 31064104] 
[105] 
Syed, D.N.; Suh, Y.; Afaq, F.; Mukhtar, H. Dietary agents for chemoprevention of prostate cancer. Cancer Lett.,  2008, 265(2), 167-176.
[http://dx.doi.org/10.1016/j.canlet.2008.02.050] [PMID: 18395333] 
[106] 
Syed, D.N.; Adhami, V.M.; Khan, M.I.; Mukhtar, H. Inhibition of Akt/mTOR signaling by the dietary flavonoid fisetin. Anticancer. Agents Med. Chem.,  2013, 13(7), 995-1001.
[http://dx.doi.org/10.2174/18715206113139990129] [PMID: 23293889] 
[107] 
Zhang, X.J.; Jia, S.S. Fisetin inhibits laryngeal carcinoma through regulation of AKT/NF-κB/mTOR and ERK1/2 signaling pathways. Biomed. Pharmacother.,  2016, 83, 1164-1174.
[http://dx.doi.org/10.1016/j.biopha.2016.08.035] [PMID: 27551764] 
[108] 
Murtaza, I.; Adhami, V.M.; Hafeez, B.B.; Saleem, M.; Mukhtar, H. Fisetin, a natural flavonoid, targets chemoresistant human pancreatic cancer AsPC-1 cells through DR3 mediated inhibition of NF-Kb. Int. J. Cancer,  2009, 125(10), 2465-2473.
[http://dx.doi.org/10.1002/ijc.24628] [PMID: 19670328] 
[109] 
Szliszka, E.; Helewski, K.J.; Mizgala, E.; Krol, W. The dietary flavonol fisetin enhances the apoptosis-inducing potential of TRAIL in prostate cancer cells. Int. J. Oncol.,  2011, 39(4), 771-779.
[PMID: 21743964] 
[110] 
Suh, Y.; Afaq, F.; Johnson, J.J.; Mukhtar, H. A plant flavonoid fisetin induces apoptosis in colon cancer cells by inhibition of COX2 and Wnt/EGFR/NF-kappaB-signaling pathways. Carcinogenesis,  2009, 30(2), 300-307.
[http://dx.doi.org/10.1093/carcin/bgn269] [PMID: 19037088] 
[111] 
Noh, E-M.; Park, Y-J.; Kim, J-M.; Kim, M-S.; Kim, H-R.; Song, H-K.; Hong, O-Y.; So, H-S.; Yang, S-H.; Kim, J-S.; Park, S.H.; Youn, H.J.; You, Y.O.; Choi, K.B.; Kwon, K.B.; Lee, Y.R. 
                        Fisetin regulates TPA-induced breast cell invasion by suppressing matrix metalloproteinase-9 activation 
                        via
                         the PKC/ROS/MAPK pathways.
                     Eur. J. Pharmacol.,  2015, 764, 79-86.
[http://dx.doi.org/10.1016/j.ejphar.2015.06.038] [PMID: 26101063] 
[112] 
Kim, J.H.; Kim, M-Y.; Kim, J-H.; Cho, J.Y. Fisetin suppresses macrophage-mediated inflammatory responses by blockade of Src and Syk. Biomol. Ther. (Seoul),  2015, 23(5), 414-420.
[http://dx.doi.org/10.4062/biomolther.2015.036] [PMID: 26336580] 
[113] 
Gelderblom, M.; Leypoldt, F.; Lewerenz, J.; Birkenmayer, G.; Orozco, D.; Ludewig, P.; Thundyil, J.; Arumugam, T.V.; Gerloff, C.; Tolosa, E.; Maher, P.; Magnus, T. The flavonoid fisetin attenuates postischemic immune cell infiltration, activation and infarct size after transient cerebral middle artery occlusion in mice. J. Cereb. Blood Flow Metab.,  2012, 32(5), 835-843.
[http://dx.doi.org/10.1038/jcbfm.2011.189] [PMID: 22234339] 
[114] 
Touil, Y.S.; Seguin, J.; Scherman, D.; Chabot, G.G. Improved antiangiogenic and antitumour activity of the combination of the natural flavonoid fisetin and cyclophosphamide in Lewis lung carcinoma-bearing mice. Cancer Chemother. Pharmacol.,  2011, 68(2), 445-455.
[http://dx.doi.org/10.1007/s00280-010-1505-8] [PMID: 21069336] 
[115] 
Li, J.; Cheng, Y.; Qu, W.; Sun, Y.; Wang, Z.; Wang, H.; Tian, B. Fisetin, a dietary flavonoid, induces cell cycle arrest and apoptosis through activation of p53 and inhibition of NF-kappa B pathways in bladder cancer cells. Basic Clin. Pharmacol. Toxicol.,  2011, 108(2), 84-93.
[http://dx.doi.org/10.1111/j.1742-7843.2010.00613.x] [PMID: 21054790] 
[116] 
Li, J.; Qu, W.; Cheng, Y.; Sun, Y.; Jiang, Y.; Zou, T.; Wang, Z.; Xu, Y.; Zhao, H. The inhibitory effect of intravesical fisetin against bladder cancer by induction of p53 and down-regulation of NF-kappa B pathways in a rat bladder carcinogenesis model. Basic Clin. Pharmacol. Toxicol.,  2014, 115(4), 321-329.
[http://dx.doi.org/10.1111/bcpt.12229] [PMID: 24646039] 
[117] 
Ying, T.H.; Yang, S.F.; Tsai, S.J.; Hsieh, S.C.; Huang, Y.C.; Bau, D.T.; Hsieh, Y.H. Fisetin induces apoptosis in human cervical cancer HeLa cells through ERK1/2-mediated activation of caspase-8-/caspase-3-dependent pathway. Arch. Toxicol.,  2012, 86(2), 263-273.
[http://dx.doi.org/10.1007/s00204-011-0754-6] [PMID: 21964635] 
[118] 
Li, H-Q.; Luo, Y.; Qiao, C-H. The mechanisms of anticancer agents by genistein and synthetic derivatives of isoflavone. Mini Rev. Med. Chem.,  2012, 12(4), 350-362.
[http://dx.doi.org/10.2174/138955712799829258] [PMID: 22303948] 
[119] 
Banerjee, S.; Li, Y.; Wang, Z.; Sarkar, F.H. Multi-targeted therapy of cancer by genistein. Cancer Lett.,  2008, 269(2), 226-242.
[http://dx.doi.org/10.1016/j.canlet.2008.03.052] [PMID: 18492603] 
[120] 
Gong, L.; Li, Y.; Nedeljkovic-Kurepa, A.; Sarkar, F.H. 
                        Inactivation of NF-kappaB by genistein is mediated 
                        via
                         Akt signaling pathway in breast cancer cells.
                     Oncogene,  2003, 22(30), 4702-4709.
[http://dx.doi.org/10.1038/sj.onc.1206583] [PMID: 12879015] 
[121] 
Pan, H.; Zhou, W.; He, W.; Liu, X.; Ding, Q.; Ling, L.; Zha, X.; Wang, S. 
                        Genistein inhibits MDA-MB-231 triple-negative breast cancer cell growth by inhibiting NF-κB activity 
                        via
                         the Notch-1 pathway.
                     Int. J. Mol. Med.,  2012, 30(2), 337-343.
[http://dx.doi.org/10.3892/ijmm.2012.990] [PMID: 22580499] 
[122] 
Luo, Y.; Wang, S-X.; Zhou, Z-Q.; Wang, Z.; Zhang, Y-G.; Zhang, Y.; Zhao, P. 
                        Apoptotic effect of genistein on human colon cancer cells 
                        via
                         inhibiting the nuclear factor-kappa B (NF-κB) pathway.
                     Tumour Biol.,  2014, 35(11), 11483-11488.
[http://dx.doi.org/10.1007/s13277-014-2487-7] [PMID: 25128065] 
[123] 
Xie, J.; Wang, J.; Zhu, B. Genistein inhibits the proliferation of human multiple myeloma cells through suppression of nuclear factor-κB and upregulation of microRNA-29b. Mol. Med. Rep.,  2016, 13(2), 1627-1632.
[http://dx.doi.org/10.3892/mmr.2015.4740] [PMID: 26718793] 
[124] 
Ozturk, S.A.; Alp, E.; Yar Saglam, A.S.; Konac, E.; Menevse, E.S. The effects of thymoquinone and genistein treatment on telomerase activity, apoptosis, angiogenesis, and survival in thyroid cancer cell lines. J. Cancer Res. Ther.,  2018, 14(2), 328-334.
[PMID: 29516914] 
[125] 
Li-Weber, M. New therapeutic aspects of flavones: the anticancer properties of Scutellaria and its main active constituents Wogonin, Baicalein and Baicalin. Cancer Treat. Rev.,  2009, 35(1), 57-68.
[http://dx.doi.org/10.1016/j.ctrv.2008.09.005] [PMID: 19004559] 
[126] 
Liu, X.; Tian, S.; Liu, M.; Jian, L.; Zhao, L. Wogonin inhibits the proliferation and invasion, and induces the apoptosis of HepG2 and Bel7402 HCC cells through NF-κB/Bcl-2, EGFR and EGFR downstream ERK/AKT signaling. Int. J. Mol. Med.,  2016, 38(4), 1250-1256.
[http://dx.doi.org/10.3892/ijmm.2016.2700] [PMID: 27499272] 
[127] 
Xu, X.; Zhang, X.; Zhang, Y.; Yang, L.; Liu, Y.; Huang, S.; Lu, L.; Kong, L.; Li, Z.; Guo, Q.; Zhao, L. 
                        Wogonin reversed resistant human myelogenous leukemia cells 
                        via
                         inhibiting Nrf2 signaling by Stat3/NF-κB inactivation.
                     Sci. Rep.,  2017, 7, 39950.
[http://dx.doi.org/10.1038/srep39950] [PMID: 28150717] 
[128] 
Yao, J.; Zhao, L.; Zhao, Q. NF-κB and Nrf2 signalling pathways contribute to wogonin-mediated inhibition of inflammation-associated colorectal carcinogenesis. Cell Death Dis.,  2014, 5, 1283-1295.
[http://dx.doi.org/10.1038/cddis.2014.221] 
[129] 
Zhao, K.; Song, X.; Huang, Y.; Yao, J.; Zhou, M.; Li, Z.; You, Q.; Guo, Q.; Lu, N. 
                        Wogonin inhibits LPS-induced tumor angiogenesis 
                        via
                         suppressing PI3K/Akt/NF-κB signaling.
                     Eur. J. Pharmacol.,  2014, 737, 57-69.
[http://dx.doi.org/10.1016/j.ejphar.2014.05.011] [PMID: 24858369] 
[130] 
Sun, J.; Li, F.; Zhao, Y. LZ-207, a newly synthesized flavonoid, induces apoptosis and suppression inflammation related colon cancer by inhibiting the NF-κB signalling pathway. PLoS One,  2015, 10, 0127282-0127300.
[131] 
Kim, H.R.; Park, C.G.; Jung, J.Y. 
                        Acacetin (5,7-dihydroxy-4′-methoxyflavone) exhibits 
                        in vitro
                         and 
                        in vivo
                         anticancer activity through the suppression of NF-κB/Akt signaling in prostate cancer cells.
                     Int. J. Mol. Med.,  2014, 33(2), 317-324.
[http://dx.doi.org/10.3892/ijmm.2013.1571] [PMID: 24285354] 
[132] 
Chen, M.; Cai, F.; Zha, D.; Wang, X.; Zhang, W.; He, Y.; Huang, Q.; Zhuang, H.; Hua, Z.C. Astragalin-induced cell death is caspase-dependent and enhances the susceptibility of lung cancer cells to tumor necrosis factor by inhibiting the NF-кB pathway. Oncotarget,  2017, 8(16), 26941-26958.
[http://dx.doi.org/10.18632/oncotarget.15264] [PMID: 28199969] 
[133] 
Wang, Y.; Hou, H.; Li, M.; Yang, Y.; Sun, L. Anticancer effect of eupatilin on glioma cells through inhibition of the Notch-1 signaling pathway. Mol. Med. Rep.,  2016, 13(2), 1141-1146.
[http://dx.doi.org/10.3892/mmr.2015.4671] [PMID: 26676446] 
[134] 
Xiao, H.S.; Xinzhong, C.; Yunhua, W.; Boyang, X.; Xuchen, C.; Oroxylin, A. 
                        Suppresses the cell proliferation, migration, and EMT 
                        via
                         NF-κB signaling pathway in human breast cancer cells.
                     BioMed Res. Int.,  2019, •••, 9241769.
[http://dx.doi.org/10.1155/2019/9241769] 
[135] 
Zhang, L.; Wen, X.; Li, M.; Li, S.; Zhao, H. Targeting cancer stem cells and signaling pathways by resveratrol and pterostilbene. Biofactors,  2018, 44(1), 61-68.
[http://dx.doi.org/10.1002/biof.1398] [PMID: 29205560] 
[136] 
Huynh, T.T.; Lin, C.M.; Lee, W.H.; Wu, A.T.; Lin, Y.K.; Lin, Y.F.; Yeh, C.T.; Wang, L.S. Pterostilbene suppressed irradiation-resistant glioma stem cells by modulating GRP78/miR-205 axis. J. Nutr. Biochem.,  2015, 26(5), 466-475.
[http://dx.doi.org/10.1016/j.jnutbio.2014.11.015] [PMID: 25736407] 
[137] 
Pei, H.L.; Mu, D.M.; Zhang, B. Anticancer activity of pterostilbene in human ovarian cancer cell lines. Med. Sci. Monit.,  2017, 23(23), 3192-3199.
[http://dx.doi.org/10.12659/MSM.901833] [PMID: 28664898] 
[138] 
Lee, J.H.; Hwang, B.Y.; Kim, K.S.; Nam, J.B.; Hong, Y.S.; Lee, J.J. 
                        Suppression of RelA/p65 transactivation activity by a lignoid manassantin isolated from 
                        Saururus chinensis. Biochem. Pharmacol.,  2003, 66(10), 1925-1933.
[http://dx.doi.org/10.1016/S0006-2952(03)00553-7] [PMID: 14599550] 
[139] 
Dhanalakshmi, S.; Singh, R.P.; Agarwal, C.; Agarwal, R. Silibinin inhibits constitutive and TNFalpha-induced activation of NF-kappaB and sensitizes human prostate carcinoma DU145 cells to TNFalpha-induced apoptosis. Oncogene,  2002, 21(11), 1759-1767.
[http://dx.doi.org/10.1038/sj.onc.1205240] [PMID: 11896607] 
[140] 
Tyagi, A.; Agarwal, C.; Dwyer-Nield, L.D.; Singh, R.P.; Malkinson, A.M.; Agarwal, R. Silibinin modulates TNF-α and IFN-γ mediated signaling to regulate COX2 and iNOS expression in tumorigenic mouse lung epithelial LM2 cells. Mol. Carcinog.,  2012, 51(10), 832-842.
[http://dx.doi.org/10.1002/mc.20851] [PMID: 21882257] 
[141] 
Tyagi, A.; Singh, R.P.; Ramasamy, K.; Raina, K.; Redente, E.F.; Dwyer-Nield, L.D.; Radcliffe, R.A.; Malkinson, A.M.; Agarwal, R. Growth inhibition and regression of lung tumors by silibinin: modulation of angiogenesis by macrophage-associated cytokines and nuclear factor-kappaB and signal transducers and activators of transcription 3. Cancer Prev. Res. (Phila.),  2009, 2(1), 74-83.
[http://dx.doi.org/10.1158/1940-6207.CAPR-08-0095] [PMID: 19139021] 
[142] 
Momeny, M.; Malehmir, M.; Zakidizaji, M.; Ghasemi, R.; Ghadimi, H.; Shokrgozar, M.A.; Emami, A.H.; Nafissi, S.; Ghavamzadeh, A.; Ghaffari, S.H. Silibinin inhibits invasive properties of human glioblastoma U87MG cells through suppression of cathepsin B and nuclear factor kappa B-mediated induction of matrix metalloproteinase 9. Anticancer Drugs,  2010, 21(3), 252-260.
[http://dx.doi.org/10.1097/CAD.0b013e3283340cd7] [PMID: 20166242] 
[143] 
Li, L.; Zeng, J.; Gao, Y.; He, D. Targeting silibinin in the antiproliferative pathway. Expert Opin. Investig. Drugs,  2010, 19(2), 243-255.
[http://dx.doi.org/10.1517/13543780903533631] [PMID: 20047507] 
[144] 
Duan, W.J.; Li, Q.S.; Xia, M.Y.; Tashiro, S.; Onodera, S.; Ikejima, T. Silibinin activated ROS-p38-NF-κB positive feedback and induced autophagic death in human fibrosarcoma HT1080 cells. J. Asian Nat. Prod. Res.,  2011, 13(1), 27-35.
[http://dx.doi.org/10.1080/10286020.2010.540757] [PMID: 21253947] 
[145] 
Raina, K.; Agarwal, C.; Agarwal, R. Effect of silibinin in human colorectal cancer cells: targeting the activation of NF-κB signaling. Mol. Carcinog.,  2013, 52(3), 195-206.
[http://dx.doi.org/10.1002/mc.21843] [PMID: 22086675] 
[146] 
Voboril, R.; Weberova-Voborilova, J. Constitutive NF-kappaB activity in colorectal cancer cells: Impact on radiation-induced NFkappaB activity, radiosensitivity, and apoptosis. Neoplasma,  2006, 53(6), 518-523.
[PMID: 17167722] 
[147] 
Harikumar, K.B.; Sung, B.; Tharakan, S.T.; Pandey, M.K.; Joy, B.; Guha, S.; Krishnan, S.; Aggarwal, B.B. Sesamin manifests chemopreventive effects through the suppression of NF-κ B-regulated cell survival, proliferation, invasion, and angiogenic gene products. Mol. Cancer Res.,  2010, 8(5), 751-761.
[http://dx.doi.org/10.1158/1541-7786.MCR-09-0565] [PMID: 20460401] 
[148] 
Xu, P.; Cai, F.; Liu, X.; Guo, L. Sesamin inhibits lipopolysaccharide-induced proliferation and invasion through the p38-MAPK and NF-κB signaling pathways in prostate cancer cells. Oncol. Rep.,  2015, 33(6), 3117-3123.
[http://dx.doi.org/10.3892/or.2015.3888] [PMID: 25845399] 
[149] 
Kong, X.; Ma, M.Z.; Zhang, Y.; Weng, M.Z.; Gong, W.; Guo, L.Q.; Zhang, J.X.; Wang, G.D.; Su, Q.; Quan, Z.W.; Yang, J.R. Differentiation therapy: Sesamin as an effective agent in targeting cancer stem-like side population cells of human gallbladder carcinoma. BMC Complement. Altern. Med.,  2014, 14, 254.
[http://dx.doi.org/10.1186/1472-6882-14-254] [PMID: 25038821] 
[150] 
Ong, C.P.; Lee, W.L.; Tang, Y.Q.; Yap, W.H. Honokiol: A review of its anticancer potential and mechanisms. Cancers (Basel),  2019, 12(1), 48.
[http://dx.doi.org/10.3390/cancers12010048] [PMID: 31877856] 
[151] 
Arora, S.; Bhardwaj, A.; Srivastava, S.K.; Singh, S.; McClellan, S.; Wang, B.; Singh, A.P. Honokiol arrests cell cycle, induces apoptosis, and potentiates the cytotoxic effect of gemcitabine in human pancreatic cancer cells. PLoS One,  2011, 6(6), e21573.
[http://dx.doi.org/10.1371/journal.pone.0021573] [PMID: 21720559] 
[152] 
Rauf, A.; Patel, S.; Imran, M.; Maalik, A.; Arshad, M.U.; Saeed, F.; Mabkhot, Y.N.; Al-Showiman, S.S.; Ahmad, N.; Elsharkawy, E. Honokiol: An anticancer lignan. Biomed. Pharmacother.,  2018, 107, 555-562.
[http://dx.doi.org/10.1016/j.biopha.2018.08.054] [PMID: 30114639] 
[153] 
Maxwell, T.; Chun, S.Y.; Lee, K.S.; Kim, S.; Nam, K.S. The anti-metastatic effects of the phytoestrogen arctigenin on human breast cancer cell lines regardless of the status of ER expression. Int. J. Oncol.,  2017, 50(2), 727-735.
[http://dx.doi.org/10.3892/ijo.2016.3825] [PMID: 28035371] 
[154] 
Keeling, C.I.; Bohlmann, J. Genes, enzymes and chemicals of terpenoid diversity in the constitutive and induced defence of conifers against insects and pathogens. New Phytol.,  2006, 170(4), 657-675.
[http://dx.doi.org/10.1111/j.1469-8137.2006.01716.x] [PMID: 16684230] 
[155] 
Dinda, B.; Debnath, S.; Harigaya, Y. Naturally occurring iridoids. A review, part 1. Chem. Pharm. Bull. (Tokyo),  2007, 55(2), 159-222.
[http://dx.doi.org/10.1248/cpb.55.159] [PMID: 17268091] 
[156] 
Chang, I.M. Liver-protective activities of aucubin derived from traditional oriental medicine. Res. Commun. Mol. Pathol. Pharmacol.,  1998, 102(2), 189-204.
[PMID: 10100510] 
[157] 
Gálvez, M.; Martín-Cordero, C.; Ayuso, M.J. Iridoids as DNA topoisomerase I poisons. J. Enzyme Inhib. Med. Chem.,  2005, 20(4), 389-392.
[http://dx.doi.org/10.1080/14756360500141879] [PMID: 16206835] 
[158] 
Berchtold, C.M.; Chen, K.S.; Miyamoto, S.; Gould, M.N. Perillyl alcohol inhibits a calcium-dependent constitutive nuclear factor-kappaB pathway. Cancer Res.,  2005, 65(18), 8558-8566.
[http://dx.doi.org/10.1158/0008-5472.CAN-04-4072] [PMID: 16166337] 
[159] 
Fraga, B.M. Natural sesquiterpenoids. Nat. Prod. Rep.,  2001, 18(6), 650-673.
[http://dx.doi.org/10.1039/b009025p] [PMID: 11820763] 
[160] 
Efferth, T. Willmar Schwabe Award 2006: Antiplasmodial and antitumor activity of artemisinin--from bench to bedside. Planta Med.,  2007, 73(4), 299-309.
[http://dx.doi.org/10.1055/s-2007-967138] [PMID: 17354163] 
[161] 
Koo, T.H.; Lee, J.H.; Park, Y.J.; Hong, Y.S.; Kim, H.S.; Kim, K.W.; Lee, J.J. 
                        A sesquiterpene lactone, costunolide, from 
                        Magnolia grandiflora
                         inhibits NF-kappa B by targeting I kappa B phosphorylation.
                     Planta Med.,  2001, 67(2), 103-107.
[http://dx.doi.org/10.1055/s-2001-11503] [PMID: 11301852] 
[162] 
Reddy, A.M.; Lee, J.Y.; Seo, J.H.; Kim, B.H.; Chung, E.Y.; Ryu, S.Y.; Kim, Y.S.; Lee, C.K.; Min, K.R.; Kim, Y. 
                        Artemisolide from 
                        Artemisia asiatica
                        : Nuclear factor-kappaB (NF-kappaB) inhibitor suppressing prostaglandin E2 and nitric oxide production in macrophages.
                     Arch. Pharm. Res.,  2006, 29(7), 591-597.
[http://dx.doi.org/10.1007/BF02969271] [PMID: 16903081] 
[163] 
Kishida, Y.; Yoshikawa, H.; Myoui, A. Parthenolide, a natural inhibitor of nuclear factor-κB, inhibits lung colonization of murine osteosarcoma cells. Clin. Cancer Res.,  2007, 13(1), 59-67.
[http://dx.doi.org/10.1158/1078-0432.CCR-06-1559] [PMID: 17200339] 
[164] 
Zhang, D.; Qiu, L.; Jin, X.; Guo, Z.; Guo, C. 
                        Nuclear Factor-κB inhibition by parthenolide potentiates the efficacy of taxol in non–small cell lung cancer 
                        in vitro
                         and 
                        in vivo
                        .
                     Cancer Mol. Cancer Res.,  2009, 7(7), 1139-1149.
[http://dx.doi.org/10.1158/1541-7786.MCR-08-0410] [PMID: 19584264] 
[165] 
Takada, Y.; Murakami, A.; Aggarwal, B.B. Zerumbone abolishes NF-kappaB and IkappaBalpha kinase activation leading to suppression of antiapoptotic and metastatic gene expression, upregulation of apoptosis, and downregulation of invasion. Oncogene,  2005, 24(46), 6957-6969.
[http://dx.doi.org/10.1038/sj.onc.1208845] [PMID: 16007145] 
[166] 
Jung, O.B.; Ju, H.O.; Bang, Y.H.; Dong, C.M.; Heon-Sang, J.; Seram, L.  Inflexinol inhibits colon cancer cell growth through inhibition of nuclear factor-κB activity via direct interaction with p50. Mol. Cancer Ther.,  2009, 8(6), 1613-1624.
[167] 
Hwang, B.Y.; Lee, J-H.; Nam, J.B.; Kim, H.S.; Hong, Y.S.; Lee, J.J. 
                        Two new furanoditerpenes from 
                        Saururus chinenesis
                         and their effects on the activation of peroxisome proliferator-activated receptor γ.
                     J. Nat. Prod.,  2002, 65(4), 616-617.
[http://dx.doi.org/10.1021/np010440j] [PMID: 11975517] 
[168] 
Hsieh, T.C.; Wijeratne, E.K.; Liang, J.Y.; Gunatilaka, A.L.; Wu, J.M. 
                        Differential control of growth, cell cycle progression, and expression of NF-kappaB in human breast cancer cells MCF-7, MCF-10A, and MDA-MB-231 by ponicidin and oridonin, diterpenoids from the chinese herb 
                        Rabdosia rubescens. Biochem. Biophys. Res. Commun.,  2005, 337(1), 224-231.
[http://dx.doi.org/10.1016/j.bbrc.2005.09.040] [PMID: 16176802] 
[169] 
Lu, Y.; Sun, Y.; Zhu, J.; Yu, L.; Jiang, X.; Zhang, J.; Dong, X.; Ma, B.; Zhang, Q. Oridonin exerts anticancer effect on osteosarcoma by activating PPAR-γ and inhibiting Nrf2 pathway. Cell Death Dis.,  2018, 9(1), 15-20.
[http://dx.doi.org/10.1038/s41419-017-0031-6] [PMID: 29323103] 
[170] 
Chao, T.H.; Lam, T.; Vong, B.G.; Través, P.G.; Hortelano, S.; Chowdhury, C.; Bahjat, F.R.; Lloyd, G.K.; Moldawer, L.L.; Boscá, L.; Palladino, M.A.; Theodorakis, E.A. A new family of synthetic diterpenes that regulates cytokine synthesis by inhibiting IkappaBalpha phosphorylation. ChemBioChem,  2005, 6(1), 133-144.
[http://dx.doi.org/10.1002/cbic.200400089] [PMID: 15540220] 
[171] 
Yan, S.S.; Li, Y.; Wang, Y.; Shen, S.S.; Gu, Y.; Wang, H.B.; Qin, G.W.; Yu, Q. 17-Acetoxyjolkinolide B irreversibly inhibits IkappaB kinase and induces apoptosis of tumor cells. Mol. Cancer Ther.,  2008, 7(6), 1523-1532.
[http://dx.doi.org/10.1158/1535-7163.MCT-08-0263] [PMID: 18566223] 
[172] 
Huang, S.C.; Ho, C.T.; Lin-Shiau, S.Y.; Lin, J.K. Carnosol inhibits the invasion of B16/F10 mouse melanoma cells by suppressing metalloproteinase-9 through down-regulating nuclear factor-kappa B and c-Jun. Biochem. Pharmacol.,  2005, 69(2), 221-232.
[http://dx.doi.org/10.1016/j.bcp.2004.09.019] [PMID: 15627474] 
[173] 
Zhuang, M.; Zhao, M.; Qiu, H.; Shi, D.; Wang, J.; Tian, Y.; Lin, L.; Deng, W. Effusanin E suppresses nasopharyngeal carcinoma cell growth by inhibiting NF-κB and COX-2 signaling. PLoS One,  2014, 9(10), e109951.
[http://dx.doi.org/10.1371/journal.pone.0109951] [PMID: 25333664] 
[174] 
Nabavi, S.M.; Habtemariam, S.; Daglia, M.; Braidy, N.; Loizzo, M.R.; Tundis, R.; Nabavi, S.F. Neuroprotective effects of ginkgolide b against ischemic stroke: A review of current literature. Curr. Top. Med. Chem.,  2015, 15(21), 2222-2232.
[http://dx.doi.org/10.2174/1568026615666150610142647] [PMID: 26059355] 
[175] 
Lou, C.; Lu, H.; Ma, Z.; Liu, C.; Zhang, Y. 
                        Ginkgolide B enhances gemcitabine sensitivity in pancreatic cancer cell lines 
                        via
                         inhibiting PAFR/NF-кB pathway.
                     Biomed. Pharmacother.,  2019, 109, 563-572.
[http://dx.doi.org/10.1016/j.biopha.2018.10.084] [PMID: 30399592] 
[176] 
Liby, K.T.; Yore, M.M.; Sporn, M.B. Triterpenoids and rexinoids as multifunctional agents for the prevention and treatment of cancer. Nat. Rev. Cancer,  2007, 7(5), 357-369.
[http://dx.doi.org/10.1038/nrc2129] [PMID: 17446857] 
[177] 
Jang, S.I.; Kim, H.J.; Kim, Y.J.; Jeong, S.I.; You, Y.O. Tanshinone IIA inhibits LPS-induced NF-kappaB activation in RAW 264.7 cells: Possible involvement of the NIK-IKK, ERK1/2, p38 and JNK pathways. Eur. J. Pharmacol.,  2006, 542(1-3), 1-7.
[http://dx.doi.org/10.1016/j.ejphar.2006.04.044] [PMID: 16797002] 
[178] 
Lee, C.Y.; Sher, H.F.; Chen, H.W.; Liu, C.C.; Chen, C.H.; Lin, C.S.; Yang, P.C.; Tsay, H.S.; Chen, J.J. Anticancer effects of tanshinone I in human non-small cell lung cancer. Mol. Cancer Ther.,  2008, 7(11), 3527-3538.
[http://dx.doi.org/10.1158/1535-7163.MCT-07-2288] [PMID: 19001436] 
[179] 
Shamon, L.A.; Pezzuto, J.M.; Graves, J.M.; Mehta, R.R.; Wangcharoentrakul, S.; Sangsuwan, R.; Chaichana, S.; Tuchinda, P.; Cleason, P.; Reutrakul, V. 
                        Evaluation of the mutagenic, cytotoxic, and antitumor potential of triptolide, a highly oxygenated diterpene isolated from 
                        Tripterygium wilfordii. Cancer Lett.,  1997, 112(1), 113-117.
[http://dx.doi.org/10.1016/S0304-3835(96)04554-5] [PMID: 9029176] 
[180] 
Zhu, W.; Hu, H.; Qiu, P.; Yan, G. Triptolide induces apoptosis in human anaplastic thyroid carcinoma cells by a p53-independent but NF-kappaB-related mechanism. Oncol. Rep.,  2009, 22(6), 1397-1401.
[PMID: 19885592] 
[181] 
Wang, Z.; Jin, H.; Xu, R.; Mei, Q.; Fan, D. Triptolide downregulates Rac1 and the JAK/STAT3 pathway and inhibits colitis-related colon cancer progression. Exp. Mol. Med.,  2009, 41(10), 717-727.
[http://dx.doi.org/10.3858/emm.2009.41.10.078] [PMID: 19561401] 
[182] 
Lee, K.Y.; Chang, W.; Qiu, D.; Kao, P.N.; Rosen, G.D. PG490 (triptolide) cooperates with tumor necrosis factor-α to induce apoptosis in tumor cells. J. Biol. Chem.,  1999, 274(19), 13451-13455.
[http://dx.doi.org/10.1074/jbc.274.19.13451] [PMID: 10224110] 
[183] 
Jiang, X.H.; Wong, B.C.Y.; Lin, M.C.M.; Zhu, G.H.; Kung, H.F.; Jiang, S.H.; Yang, D.; Lam, S.K. Functional p53 is required for triptolide-induced apoptosis and AP-1 and nuclear factor-kappaB activation in gastric cancer cells. Oncogene,  2001, 20(55), 8009-8018.
[http://dx.doi.org/10.1038/sj.onc.1204981] [PMID: 11753684] 
[184] 
Kang, D.W.; Lee, J.Y.; Oh, D.H.; Park, S.Y.; Woo, T.M.; Kim, M.K.; Park, M.H.; Jang, Y.H.; Min, S. Triptolide-induced suppression of phospholipase D expression inhibits proliferation of MDA-MB-231 breast cancer cells. Exp. Mol. Med.,  2009, 41(9), 678-685.
[http://dx.doi.org/10.3858/emm.2009.41.9.074] [PMID: 19478552] 
[185] 
Radad, K.; Gille, G.; Liu, L.; Rausch, W.D. Use of ginseng in medicine with emphasis on neurodegenerative disorders. J. Pharmacol. Sci.,  2006, 100(3), 175-186.
[http://dx.doi.org/10.1254/jphs.CRJ05010X] [PMID: 16518078] 
[186] 
Heber, D.; Lu, Q.Y. Overview of mechanisms of action of lycopene. Exp. Biol. Med. (Maywood),  2002, 227, 920-923.
[http://dx.doi.org/10.1177/153537020222701013] 
[187] 
Haridas, V.; Arntzen, C.J.; Gutterman, J.U. 
                        Avicins, a family of triterpenoid saponins from 
                        Acacia victoriae
                         (Bentham), inhibit activation of nuclear factor-B by inhibiting both its nuclear localization and ability to bind DNA.
                     Proc. Natl. Acad. Sci. USA,  2001, 98, 11557-11562.
[http://dx.doi.org/10.1073/pnas.191363498] [PMID: 11572998] 
[188] 
Takada, Y.; Aggarwal, B.B. Betulinic acid suppresses carcinogen-induced NF-kappa B activation through inhibition of I kappa B alpha kinase and p65 phosphorylation: abrogation of cyclooxygenase-2 and matrix metalloprotease-9. J. Immunol.,  2003, 171(6), 3278-3286.
[http://dx.doi.org/10.4049/jimmunol.171.6.3278] [PMID: 12960358] 
[189] 
Keum, Y.S.; Han, S.S.; Chun, K.S.; Park, K.K.; Park, J.H.; Lee, S.K.; Surh, Y.J. Inhibitory effects of the ginsenoside Rg3 on phorbol ester-induced cyclooxygenase-2 expression, NF-kappaB activation and tumor promotion. Mutat. Res.,  2003, 523-524, 75-85.
[http://dx.doi.org/10.1016/S0027-5107(02)00323-8] [PMID: 12628505] 
[190] 
Lee, T.K.; Poon, R.T.P.; Wo, J.Y.; Ma, S.; Guan, X.Y.; Myers, J.N.; Altevogt, P.; Yuen, A.P. Lupeol suppresses cisplatin-induced nuclear factor-kappaB activation in head and neck squamous cell carcinoma and inhibits local invasion and nodal metastasis in an orthotopic nude mouse model. Cancer Res.,  2007, 67(18), 8800-8809.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-0801] [PMID: 17875721] 
[191] 
Saleem, M.; Afaq, F.; Adhami, V.M.; Mukhtar, H. Lupeol modulates NF-kappaB and PI3K/Akt pathways and inhibits skin cancer in CD-1 mice. Oncogene,  2004, 23(30), 5203-5214.
[http://dx.doi.org/10.1038/sj.onc.1207641] [PMID: 15122342] 
[192] 
Liu, J. Pharmacology of oleanolic acid and ursolic acid. J. Ethnopharmacol.,  1995, 49(2), 57-68.
[http://dx.doi.org/10.1016/0378-8741(95)90032-2] [PMID: 8847885] 
[193] 
Shishodia, S.; Majumdar, S.; Banerjee, S.; Aggarwal, B.B. Ursolic acid inhibits nuclear factor-kappaB activation induced by carcinogenic agents through suppression of IkappaBalpha kinase and p65 phosphorylation: Correlation with down-regulation of cyclooxygenase 2, matrix metalloproteinase 9, and cyclin D1. Cancer Res.,  2003, 63(15), 4375-4383.
[PMID: 12907607] 
[194] 
De Stefano, D.; Maiuri, M.C.; Simeon, V.; Grassia, G.; Soscia, A.; Cinelli, M.P.; Carnuccio, R. Lycopene, quercetin and tyrosol prevent macrophage activation induced by gliadin and IFN-gamma. Eur. J. Pharmacol.,  2007, 566(1-3), 192-199.
[http://dx.doi.org/10.1016/j.ejphar.2007.03.051] [PMID: 17477920] 
[195] 
Krinsky, N.I.; Johnson, E.J. Carotenoid actions and their relation to health and disease. Mol. Aspects Med.,  2005, 26, 459-516.
[196] 
Ahn, K.S.; Sethi, G.; Aggarwal, B.B. Embelin, an inhibitor of X chromosome-linked inhibitor-of-apoptosis protein, blocks nuclear factor-kappaB (NF-kappaB) signaling pathway leading to suppression of NF-kappaB-regulated antiapoptotic and metastatic gene products. Mol. Pharmacol.,  2007, 71(1), 209-219.
[http://dx.doi.org/10.1124/mol.106.028787] [PMID: 17028156] 
[197] 
Sang-Yoon, P.; Sung-Lyul, L.; Hyeung-Jin, J.; Jun-Hee, L.; Jae-Young, U.; Sung-Hoon, K.; Kwang Seok, A.; Seok-Geun, L. Cells through inactivating NF-κB. J. Pharmacol. Sci.,  2013, 121, 192-199.
[http://dx.doi.org/10.1254/jphs.12137FP] 
[198] 
Xu, C.L.; Zheng, B.; Pei, J.H.; Shen, S.J.; Wang, J.Z. Embelin induces apoptosis of human gastric carcinoma through inhibition of p38 MAPK and NF-κB signaling pathways. Mol. Med. Rep.,  2016, 14(1), 307-312.
[http://dx.doi.org/10.3892/mmr.2016.5232] [PMID: 27175982] 
[199] 
Liu, H.; Li, G.; Zhang, B.; Sun, D.; Wu, J.; Chen, F.; Kong, F.; Luan, Y.; Jiang, W.; Wang, R.; Xue, X. Suppression of the NF-κB signaling pathway in colon cancer cells by the natural compound Riccardin D from Dumortierahirsute. Mol. Med. Rep.,  2018, 17(4), 5837-5843.
[http://dx.doi.org/10.3892/mmr.2018.8617] [PMID: 29484409] 
[200] 
Susanne, C.M.; Huang, R.; Sakamuru, S.; Susanne, C.M.; Shukla, S.J. AtteneRamos, M.S.; Shinn, P.; Leer, D.V.; Leister, W.; Austin, C.P.; Xia, M. Identification of known drugs that act as inhibitors of NF-κB signalling and their mechanism of action. Biochem. Pharmacol.,  2010, 79(9), 1272-1280.
[PMID: 20067776] 
[201] 
Lu, K.W.; Chen, J.C.; Lai, T.Y.; Yang, J.S.; Weng, S.W.; Ma, Y.S.; Lu, P.J.; Weng, J.R.; Chueh, F.S.; Wood, W.G.; Chung, J.G. Gypenosides inhibits migration and invasion of human oral cancer SAS cells through the inhibition of matrix metalloproteinase-2 -9 and urokinase-plasminogen by ERK1/2 and NF-kappa B signaling pathways. Hum. Exp. Toxicol.,  2011, 30(5), 406-415.
[http://dx.doi.org/10.1177/0960327110372405] [PMID: 20511288] 
[202] 
Ling, H.; Zhang, Y.; Ng, K.Y.; Chew, E.H. Pachymic acid impairs breast cancer cell invasion by suppressing nuclear factor-κB-dependent matrix metalloproteinase-9 expression. Breast Cancer Res. Treat.,  2011, 126(3), 609-620.
[http://dx.doi.org/10.1007/s10549-010-0929-5] [PMID: 20521099] 
[203] 
Ikezoe, T.; Yang, Y.; Saitoh, T.; Heber, D.; McKenna, R.; Taguchi, H.; Koeffler, H.P. PC-SPES down-regulates COX-2 via inhibition of NF-kappaB and C/EBPbeta in non-small cell lung cancer cells. Int. J. Oncol.,  2006, 29(2), 453-461.
[PMID: 16820889] 
[204] 
Woo, S-M.; Choi, Y.K.; Park, S.; Ko, S-G. A new herbal formula, KSG-002, suppresses breast cancer growth and metastasis by targeting NF-kb-dependent TNFα production in macrophages. Evid. Based Complement. Alternat. Med.,  2013, 2013, 728258.
[205] 
Pozdeyev, N.; Berlinberg, A.; Zhou, Q.; Wuensch, K.; Shibata, H.; Wood, W.M.; Haugen, B.R. Targeting the NF-κB pathway as a combination therapy for advanced thyroid cancer. PLoS One,  2015, 10(8), e0134901.
[http://dx.doi.org/10.1371/journal.pone.0134901] [PMID: 26263379] 
[206] 
Paur, I.; Balstad, T.R. Kolberg1, M.; Pedersen, M.K.; Liv, M.; Austenaa, M.; Jacobs, Jr., D.R.; Blomhoff, R. Extract of oregano, coffee, thyme, clove, and walnuts inhibits NF-κB in monocytes andin transgenic reporter mice Cancer Prev. Res. (Phila.),  3(5), 653-663.
[207] 
Li, X.; Guo, S.; Xiong, X.K.; Peng, B.Y.; Huang, J.M.; Chen, M.F.; Wang, F.Y.; Wang, J.N. Combination of quercetin and cisplatin enhances apoptosis in OSCC cells by downregulating xIAP through the NF-κB pathway. J. Cancer,  2019, 10(19), 4509-4521.
[http://dx.doi.org/10.7150/jca.31045] [PMID: 31528215] 
[208] 
Yi, C.; Zhang, Y.; Yu, Z.; Xiao, Y.; Wang, J.; Qiu, H.; Yu, W.; Tang, R.; Yuan, Y.; Guo, W.; Deng, W. Melatonin enhances the anti-tumor effect of fisetin by inhibiting COX-2/iNOS and NF-κB/p300 signaling pathways. PLoS One,  2014, 9(7), e99943.
[http://dx.doi.org/10.1371/journal.pone.0099943] [PMID: 25000190] 
[209] 
Julian, J. Raffoul; Wang, Y.; Kucuk, O.; Forman, J.D; Sarkar, F.H.; Hillman, G.G. Genistein inhibits radiation-induced activation of NF-κB in prostate cancer cells promoting apoptosis and G2/M cell cycle arrest. BMC Cancer,  2006, 6, 107.
[http://dx.doi.org/10.1186/1471-2407-6-107] 
[210] 
Singh, R.P.; Mallikarjuna, G.U.; Sharma, G.; Dhanalakshmi, S.; Tyagi, A.K.; Chan, D.C.; Agarwal, C.; Agarwal, R. Oral silibinin inhibits lung tumor growth in athymic nude mice and forms a novel chemocombination with doxorubicin targeting nuclear factor kappaB-mediated inducible chemoresistance. Clin. Cancer Res.,  2004, 10(24), 8641-8647.
[http://dx.doi.org/10.1158/1078-0432.CCR-04-1435] [PMID: 15623648] 
[211] 
Itsuro, S.; Yoshiyuki, F.; Yurika, S.; Akiko, Y.; Mitsuhiro, S.; Jeong-Ho, M. Parthenolide, an NF-κB inhibitor, suppresses tumor growth and enhances response to chemotherapy in gastric cancer, cancer genomics and proteomics. Cancer Genomics Proteomics,  2011, 8(1), 39-47.
[212] 
Pazhang, Y.; Jaliani, H.Z.; Imani, M.; Dariushnejad, H. Synergism between NF-kappa B inhibitor, celastrol, and XIAP inhibitor, embelin, in an acute myeloid leukemia cell line, HL-60. J. Cancer Res. Ther.,  2016, 12(1), 155-160.
[http://dx.doi.org/10.4103/0973-1482.150407] [PMID: 27072230] 
Rights & Permissions Print Cite
Article Metrics
69
1
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/1389557522666220307170126	Print ISSN 1389-5575
Publisher Name Bentham Science Publisher	Online ISSN 1875-5607
Mini-Reviews in Medicinal Chemistry

Medicinal Plants in Cancer Treatment: Contribution of Nuclear Factor- Kappa B (NF-kB) Inhibitors

Abstract

Graphical Abstract

Bioprospecting of Natural Products as Sources of New Multitarget Therapies

Computational Frontiers in Medicinal Chemistry

Drugs and mitochondria

Mitochondria as a Therapeutic Target in Metabolic Disorders

Mini-Reviews in Medicinal Chemistry

Medicinal Plants in Cancer Treatment: Contribution of Nuclear Factor- Kappa B (NF-kB) Inhibitors

Abstract

Graphical Abstract

Call for Papers in Thematic Issues

Bioprospecting of Natural Products as Sources of New Multitarget Therapies

Computational Frontiers in Medicinal Chemistry

Drugs and mitochondria

Mitochondria as a Therapeutic Target in Metabolic Disorders

Related Journals

Related Books

Related Articles
