Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Systematic Review Article

The Radiosensitizing Potentials of Silymarin/Silibinin in Cancer: A Systematic Review

Author(s): Jitendra Gupta, Abduladheem Turki Jalil*, Zainab Al-hawraa Riyad Muedii, Zafar Aminov, Fahad Alsaikhan*, Andrés Alexis Ramírez-Coronel, Pushpamala Ramaiah and Bagher Farhood*

Volume 31, Issue 42, 2024

Published on: 26 October, 2023

Page: [6992 - 7014] Pages: 23

DOI: 10.2174/0109298673248404231006052436

Price: $65

Open Access Journals Promotions 2
conference banner
Abstract

Introduction: Although radiotherapy is one of the main cancer treatment modalities, exposing healthy organs/tissues to ionizing radiation during treatment and tumor resistance to ionizing radiation are the chief challenges of radiotherapy that can lead to different adverse effects. It was shown that the combined treatment of radiotherapy and natural bioactive compounds (such as silymarin/silibinin) can alleviate the ionizing radiation-induced adverse side effects and induce synergies between these therapeutic modalities. In the present review, the potential radiosensitization effects of silymarin/silibinin during cancer radiation exposure/radiotherapy were studied.

Methods: According to the PRISMA guideline, a systematic search was performed for the identification of relevant studies in different electronic databases of Google Scholar, PubMed, Web of Science, and Scopus up to October 2022. We screened 843 articles in accordance with a predefined set of inclusion and exclusion criteria. Seven studies were finally included in this systematic review.

Results: Compared to the control group, the cell survival/proliferation of cancer cells treated with ionizing radiation was considerably less, and silymarin/silibinin administration synergistically increased ionizing radiation-induced cytotoxicity. Furthermore, there was a decrease in the tumor volume, weight, and growth of ionizing radiation-treated mice as compared to the untreated groups, and these diminutions were predominant in those treated with radiotherapy plus silymarin/ silibinin. Furthermore, the irradiation led to a set of biochemical and histopathological changes in tumoral cells/tissues, and the ionizing radiation-induced alterations were synergized following silymarin/silibinin administration (in most cases).

Conclusion: In most cases, silymarin/silibinin administration could sensitize the cancer cells to ionizing radiation through an increase of free radical formation, induction of DNA damage, increase of apoptosis, inhibition of angiogenesis and metastasis, etc. However, suggesting the use of silymarin/silibinin during radiotherapeutic treatment of cancer patients requires further clinical studies.

Keywords: Cancer, radiotherapy, radiosensitization, silymarin, silibinin, systematic review.

« Previous Next »
[1]
Farhood, B.; Geraily, G.; Alizadeh, A. Incidence and mortality of various cancers in Iran and compare to other countries: A review article. Iran. J. Public Health, 2018, 47(3), 309-316.
[PMID: 29845017]
[2]
Mortezaee, K.; Narmani, A.; Salehi, M.; Bagheri, H.; Farhood, B.; Haghi-Aminjan, H.; Najafi, M. Synergic effects of nanoparticles-mediated hyperthermia in radiotherapy/chemotherapy of cancer. Life Sci., 2021, 269, 119020.
[http://dx.doi.org/10.1016/j.lfs.2021.119020] [PMID: 33450258]
[3]
Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2021, 71(3), 209-249.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[4]
Najafi, M.; Hooshangi Shayesteh, M.R.; Mortezaee, K.; Farhood, B.; Haghi-Aminjan, H. The role of melatonin on doxorubicin-induced cardiotoxicity: A systematic review. Life Sci., 2020, 241, 117173.
[http://dx.doi.org/10.1016/j.lfs.2019.117173] [PMID: 31843530]
[5]
Talakesh, T.; Tabatabaee, N.; Atoof, F.; Aliasgharzadeh, A.; Sarvizade, M.; Farhood, B. Effect of nano-curcumin on radiotherapy-induced skin reaction in breast cancer patients: A randomized, triple-blind, placebo-controlled trial. Curr Radiopharm., 2022, 15(4), 332-340.
[6]
Mortezaee, K.; Parwaie, W.; Motevaseli, E.; Mirtavoos-Mahyari, H.; Musa, A.E.; Shabeeb, D.; Esmaely, F.; Najafi, M.; Farhood, B. Targets for improving tumor response to radiotherapy. Int. Immunopharmacol., 2019, 76, 105847.
[http://dx.doi.org/10.1016/j.intimp.2019.105847] [PMID: 31466051]
[7]
Ford, E.C.; Terezakis, S. How safe is safe? Risk in radiotherapy. Int. J. Radiat. Oncol. Biol. Phys., 2010, 78(2), 321-322.
[http://dx.doi.org/10.1016/j.ijrobp.2010.04.047] [PMID: 20832662]
[8]
Baskar, R.; Lee, K.A.; Yeo, R.; Yeoh, K.W. Cancer and radiation therapy: current advances and future directions. Int. J. Med. Sci., 2012, 9(3), 193-199.
[http://dx.doi.org/10.7150/ijms.3635] [PMID: 22408567]
[9]
Mortezaee, K.; Najafi, M.; Farhood, B.; Ahmadi, A.; Shabeeb, D.; Musa, A.E. Resveratrol as an adjuvant for normal tissues protection and tumor sensitization. Curr. Cancer Drug Targets, 2020, 20(2), 130-145.
[http://dx.doi.org/10.2174/1568009619666191019143539] [PMID: 31738153]
[10]
Farhood, B.; Geraily, G.; Abtahi, S.M.M. A systematic review of clinical applications of polymer gel dosimeters in radiotherapy. Appl. Radiat. Isot., 2019, 143, 47-59.
[http://dx.doi.org/10.1016/j.apradiso.2018.08.018] [PMID: 30390500]
[11]
Bagheri, H.; Rabie Mahdavi, S.; Shekarchi, B.; Manouchehri, F.; Farhood, B. Measurement of the contralateral breast photon and thermal neutron doses in breast cancer radiotherapy: A comparison between physical and dynamic wedges. Radiat. Prot. Dosimetry, 2018, 178(1), 73-81.
[http://dx.doi.org/10.1093/rpd/ncx076] [PMID: 28591863]
[12]
Moding, E.J.; Kastan, M.B.; Kirsch, D.G. Strategies for optimizing the response of cancer and normal tissues to radiation. Nat. Rev. Drug Discov., 2013, 12(7), 526-542.
[http://dx.doi.org/10.1038/nrd4003] [PMID: 23812271]
[13]
Mortezaee, K.; Salehi, E.; Mirtavoos-mahyari, H.; Motevaseli, E.; Najafi, M.; Farhood, B.; Rosengren, R.J.; Sahebkar, A. Mechanisms of apoptosis modulation by curcumin: Implications for cancer therapy. J. Cell. Physiol., 2019, 234(8), 12537-12550.
[http://dx.doi.org/10.1002/jcp.28122] [PMID: 30623450]
[14]
Liauw, S.L.; Connell, P.P.; Weichselbaum, R.R. New paradigms and future challenges in radiation oncology: An update of biological targets and technology. Sci. Transl. Med., 2013, 5(173), 173sr2.
[http://dx.doi.org/10.1126/scitranslmed.3005148] [PMID: 23427246]
[15]
Farhood, B.; Goradel, N.H.; Mortezaee, K.; Khanlarkhani, N.; Salehi, E.; Nashtaei, M.S.; Mirtavoos-mahyari, H.; Motevaseli, E.; Shabeeb, D.; Musa, A.E.; Najafi, M. Melatonin as an adjuvant in radiotherapy for radioprotection and radiosensitization. Clin. Transl. Oncol., 2019, 21(3), 268-279.
[http://dx.doi.org/10.1007/s12094-018-1934-0] [PMID: 30136132]
[16]
Mortezaee, K.; Shabeeb, D.; Musa, A.E.; Najafi, M.; Farhood, B. Metformin as a radiation modifier; implications to normal tissue protection and tumor sensitization. Curr. Clin. Pharmacol., 2019, 14(1), 41-53.
[http://dx.doi.org/10.2174/1574884713666181025141559] [PMID: 30360725]
[17]
Narmani, A.; Farhood, B.; Haghi-Aminjan, H.; Mortezazadeh, T.; Aliasgharzadeh, A.; Mohseni, M.; Najafi, M.; Abbasi, H. Gadolinium nanoparticles as diagnostic and therapeutic agents: Their delivery systems in magnetic resonance imaging and neutron capture therapy. J. Drug Deliv. Sci. Technol., 2018, 44, 457-466.
[http://dx.doi.org/10.1016/j.jddst.2018.01.011]
[18]
Alireza, G.; Bagher, F.; Farshid, A.N. Histopathological evaluation of nanocurcumin for mitigation of radiation-induced small intestine injury. Curr Radiopharm., 2022, 16(1), 57-63.
[19]
Najafi, M.; Taeb, S.; Farhood, B.; Amini, P.; Nodooshan, S.J.; Ashrafizadeh, M.; Aliasgharzadeh, A.; Vakili, Z.; Tavakoli, S.; Aryafar, T.; Musa, A.E. Imperatorin attenuates the proliferation of MCF-7 cells in combination with radiotherapy or hyperthermia. Curr. Radiopharm., 2022, 15(3), 236-241.
[http://dx.doi.org/10.2174/1874471015666220318122202] [PMID: 35306999]
[20]
Nodooshan, S.J.; Amini, P.; Ashrafizadeh, M.; Tavakoli, S.; Aryafar, T.; Khalafi, L.; Musa, A.E.; Mahdavi, S.R.; Najafi, M.; Ahmadi, A.; Farhood, B. Suberosin attenuates the proliferation of MCF-7 breast cancer cells in combination with radiotherapy or hyperthermia. Curr. Drug Res. Rev., 2021, 13(2), 148-153.
[http://dx.doi.org/10.2174/2589977512666201228104528] [PMID: 33371865]
[21]
Farhood, B.; Hassanzadeh, G.; Amini, P.; Shabeeb, D.; Musa, A.E.; Khodamoradi, E.; Mohseni, M.; Aliasgharzadeh, A.; Moradi, H.; Najafi, M. Mitigation of radiation-induced gastrointestinal system injury using resveratrol or alpha-lipoic acid: A pilot histopathological study. Antiinflamm. Antiallergy Agents Med. Chem., 2020, 19(4), 413-424.
[http://dx.doi.org/10.2174/1871523018666191111124028] [PMID: 31713500]
[22]
Motallebzadeh, E.; Tameh, A.A.; Zavareh, S.A.T.; Farhood, B.; Aliasgharzedeh, A.; Mohseni, M. Neuroprotective effect of melatonin on radiation-induced oxidative stress and apoptosis in the brainstem of rats. J. Cell. Physiol., 2020, 235(11), 8791-8798.
[http://dx.doi.org/10.1002/jcp.29722] [PMID: 32324264]
[23]
Yahyapour, R.; Amini, P.; Saffar, H.; Motevaseli, E.; Farhood, B.; Pooladvand, V.; Shabeeb, D.; Musa, A.E.; Najafi, M. Protective effect of metformin, resveratrol and alpha-lipoic acid on radiation- induced pneumonitis and fibrosis: A histopathological study. Curr. Drug Res. Rev., 2019, 11(2), 111-117.
[http://dx.doi.org/10.2174/2589977511666191018180758] [PMID: 31875783]
[24]
Khezerloo, D.; Mortezazadeh, T.; Farhood, B.; Sheikhzadeh, P.; Seyfizadeh, N.; Pezhman, L. The effect of date palm seed extract as a new potential radioprotector in gamma-irradiated mice. J. Cancer Res. Ther., 2019, 15(3), 517-521.
[http://dx.doi.org/10.4103/jcrt.JCRT_1341_16] [PMID: 31169213]
[25]
Aliasgharzadeh, A.; Farhood, B.; Amini, P.; Saffar, H.; Motevaseli, E.; Rezapoor, S.; Nouruzi, F.; Shabeeb, D.H.; Eleojo Musa, A.; Mohseni, M.; Moradi, H.; Najafi, M. Melatonin attenuates upregulation of Duox1 and Duox2 and protects against lung injury following chest irradiation in rats. Cell J., 2019, 21(3), 236-242.
[PMID: 31210428]
[26]
Azmoonfar, R.; Amini, P.; Saffar, H.; Rezapoor, S.; Motevaseli, E.; Cheki, M.; Yahyapour, R.; farhood, B.; Nouruzi, F.; Khodamoradi, E.; Shabeeb, D.; Eleojo Musa, A.; Najafi, M. Metformin protects against radiation-induced pneumonitis and fibrosis and attenuates upregulation of dual oxidase genes expression. Adv. Pharm. Bull., 2018, 8(4), 697-704.
[http://dx.doi.org/10.15171/apb.2018.078] [PMID: 30607342]
[27]
Farhood, B.; Aliasgharzadeh, A.; Amini, P.; Saffar, H.; Motevaseli, E.; Rezapoor, S.; Nouruzi, F.; Shabeeb, D.; Eleojo Musa, A.; Ashabi, G.; Mohseni, M.; Moradi, H.; Najafi, M. Radiation-induced dual oxidase upregulation in rat heart tissues: Protective effect of melatonin. Medicina, 2019, 55(7), 317.
[http://dx.doi.org/10.3390/medicina55070317] [PMID: 31252673]
[28]
Najafi, M.; Motevaseli, E.; Shirazi, A.; Geraily, G.; Rezaeyan, A.; Norouzi, F.; Rezapoor, S.; Abdollahi, H. Mechanisms of inflammatory responses to radiation and normal tissues toxicity: clinical implications. Int. J. Radiat. Biol., 2018, 94(4), 335-356.
[http://dx.doi.org/10.1080/09553002.2018.1440092] [PMID: 29504497]
[29]
Allison, R.; Dicker, A. Minimizing morbidity in radiation oncology: a special issue from future oncology. Future Oncol., 2014, 10(15), 2303-2305.
[http://dx.doi.org/10.2217/fon.14.195] [PMID: 25525839]
[30]
Arabzadeh, A.; Mortezazadeh, T.; Aryafar, T.; Gharepapagh, E.; Majdaeen, M.; Farhood, B. Therapeutic potentials of resveratrol in combination with radiotherapy and chemotherapy during glioblastoma treatment: A mechanistic review. Cancer Cell Int., 2021, 21(1), 391.
[http://dx.doi.org/10.1186/s12935-021-02099-0] [PMID: 34289841]
[31]
Sheikholeslami, S.; Khodaverdian, S.; Dorri-Giv, M.; Mohammad Hosseini, S.; Souri, S.; Abedi-Firouzjah, R.; Zamani, H.; Dastranj, L.; Farhood, B. The radioprotective effects of alpha-lipoic acid on radiotherapy-induced toxicities: A systematic review. Int. Immunopharmacol., 2021, 96, 107741.
[http://dx.doi.org/10.1016/j.intimp.2021.107741] [PMID: 33989970]
[32]
Amini, P.; Nodooshan, S.J.; Ashrafizadeh, M.; Eftekhari, S-M.; Aryafar, T.; Khalafi, L.; Musa, A.E.; Mahdavi, S.R.; Najafi, M.; Farhood, B. Resveratrol induces apoptosis and attenuates proliferation of MCF-7 cells in combination with radiation and hyperthermia. Curr. Mol. Med., 2021, 21(2), 142-150.
[http://dx.doi.org/10.2174/18755666MTA2pODE0z] [PMID: 32436827]
[33]
Ahmed, R.F.; Moussa, R.A.; Eldemerdash, R.S.; Zakaria, M.M.; Abdel-Gaber, S.A. Ameliorative effects of silymarin on HCl-induced acute lung injury in rats; role of the Nrf-2/HO-1 pathway. Iran. J. Basic Med. Sci., 2019, 22(12), 1483-1492.
[PMID: 32133068]
[34]
Comelli, M.C.; Mengs, U.; Schneider, C.; Prosdocimi, M. Toward the definition of the mechanism of action of silymarin: Activities related to cellular protection from toxic damage induced by chemotherapy. Integr. Cancer Ther., 2007, 6(2), 120-129.
[http://dx.doi.org/10.1177/1534735407302349] [PMID: 17548791]
[35]
de Oliveira, D.R.; Tintino, S.R.; Braga, M.F.; Boligon, A.A.; Athayde, M.L.; Coutinho, H.D.; de Menezes, I.R.; Fachinetto, R. In vitro antimicrobial and modulatory activity of the natural products silymarin and silibinin. BioMed Res. Int., 2015, 2015, 292797.
[PMID: 25866771]
[36]
Ferenci, P. Silymarin in the treatment of liver diseases: What is the clinical evidence? Clin. Liver Dis., 2016, 7(1), 8-10.
[http://dx.doi.org/10.1002/cld.522] [PMID: 31041017]
[37]
Ferenci, P.; Dragosics, B.; Dittrich, H.; Frank, H.; Benda, L.; Lochs, H.; Meryn, S.; Base, W.; Schneider, B. Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J. Hepatol., 1989, 9(1), 105-113.
[http://dx.doi.org/10.1016/0168-8278(89)90083-4] [PMID: 2671116]
[38]
Abenavoli, L.; Milic, N. Silymarin for liver disease. In: Liver Pathophysiology; Muriel, P., Ed.; Academic Press: Boston, 2017; pp. 621-631.
[http://dx.doi.org/10.1016/B978-0-12-804274-8.00045-X]
[39]
Gazák, R.; Walterová, D.; Kren, V. Silybin and silymarin--new and emerging applications in medicine. Curr. Med. Chem., 2007, 14(3), 315-338.
[http://dx.doi.org/10.2174/092986707779941159] [PMID: 17305535]
[40]
Testino, G.; Leone, S.; Ansaldi, F.; Borro, P. Silymarin and S-adenosyl-L-methionine (SAMe): Two promising pharmacological agents in case of chronic alcoholic hepathopathy. A review and a point of view. Minerva Gastroenterol. Dietol., 2013, 59(4), 341-356.
[PMID: 24212353]
[41]
Zholobenko, A.; Modriansky, M. Silymarin and its constituents in cardiac preconditioning. Fitoterapia, 2014, 97, 122-132.
[http://dx.doi.org/10.1016/j.fitote.2014.05.016] [PMID: 24879900]
[42]
Vargas-Mendoza, N.; Madrigal-Santillán, E.; Morales-González, A.; Esquivel-Soto, J.; Esquivel-Chirino, C.; García-Luna Y González-Rubio, M.; Gayosso-de-Lucio, J.A.; Morales-González, J.A. Hepatoprotective effect of silymarin. World J. Hepatol., 2014, 6(3), 144-149.
[http://dx.doi.org/10.4254/wjh.v6.i3.144] [PMID: 24672644]
[43]
Surai, P. Silymarin as a natural antioxidant: An overview of the current evidence and perspectives. Antioxidants, 2015, 4(1), 204-247.
[http://dx.doi.org/10.3390/antiox4010204] [PMID: 26785346]
[44]
Guzel, S.; Sahinogullari, Z.U.; Canacankatan, N.; Antmen, S.E.; Kibar, D.; Coskun Yilmaz, B. Potential renoprotective effects of silymarin against vancomycin-induced nephrotoxicity in rats. Drug Chem. Toxicol., 2020, 43(6), 630-636.
[http://dx.doi.org/10.1080/01480545.2019.1584208] [PMID: 30862206]
[45]
Zhu, Z.; Sun, G. Silymarin mitigates lung impairments in a rat model of acute respiratory distress syndrome. Inflammopharmacology, 2018, 26(3), 747-754.
[http://dx.doi.org/10.1007/s10787-017-0407-3] [PMID: 29098546]
[46]
Singh, M.; Kadhim, M.M.; Turki Jalil, A.; Oudah, S.K.; Aminov, Z.; Alsaikhan, F.; Jawhar, Z.H.; Ramírez-Coronel, A.A.; Farhood, B. A systematic review of the protective effects of silymarin/silibinin against doxorubicin-induced cardiotoxicity. Cancer Cell Int., 2023, 23(1), 88.
[http://dx.doi.org/10.1186/s12935-023-02936-4] [PMID: 37165384]
[47]
Taleb, A; Ahmad, KA; Ihsan, AU; Qu, J; Lin, N; Hezam, K Antioxidant effects and mechanism of silymarin in oxidative stress induced cardiovascular diseases. Biomed. Pharmacother., 2018, 102, 689-698.
[http://dx.doi.org/10.1016/j.biopha.2018.03.140]
[48]
Ferraz, A.C.; Almeida, L.T.; da Silva Caetano, C.C.; da Silva Menegatto, M.B.; Souza Lima, R.L.; de Senna, J.P.N.; de Oliveira Cardoso, J.M.; Perucci, L.O.; Talvani, A.; Geraldo de Lima, W.; de Mello Silva, B.; Barbosa Reis, A.; de Magalhães, J.C.; Lopes de Brito Magalhães, C. Hepatoprotective, antioxidant, anti-inflammatory, and antiviral activities of silymarin against mayaro virus infection. Antiviral Res., 2021, 194, 105168.
[http://dx.doi.org/10.1016/j.antiviral.2021.105168] [PMID: 34437912]
[49]
Post-White, J.; Ladas, E.J.; Kelly, K.M. Advances in the use of milk thistle (Silybum marianum). Integr. Cancer Ther., 2007, 6(2), 104-109.
[http://dx.doi.org/10.1177/1534735407301632] [PMID: 17548789]
[50]
Hosseinabadi, T.; Lorigooini, Z.; Tabarzad, M.; Salehi, B.; Rodrigues, C.F.; Martins, N.; Sharifi-Rad, J. Silymarin antiproliferative and apoptotic effects: Insights into its clinical impact in various types of cancer. Phytother. Res., 2019, 33(11), 2849-2861.
[http://dx.doi.org/10.1002/ptr.6470] [PMID: 31407422]
[51]
Abd Eldaim, M.A.; Barakat, E.R.; Alkafafy, M.; Elaziz, S.A.A. Antioxidant and anti-apoptotic prophylactic effect of silymarin against lead-induced hepatorenal toxicity in rats. Environ. Sci. Pollut. Res. Int., 2021, 28(41), 57997-58006.
[http://dx.doi.org/10.1007/s11356-021-14722-8] [PMID: 34100211]
[52]
Barros, T.M.B.; Lima, A.P.B.; Almeida, T.C.; da Silva, G.N. Inhibition of urinary bladder cancer cell proliferation by silibinin. Environ. Mol. Mutagen., 2020, 61(4), 445-455.
[http://dx.doi.org/10.1002/em.22363] [PMID: 32078183]
[53]
Yu, H.C.; Chen, L.J.; Cheng, K.C.; Li, Y.X.; Yeh, C.H.; Cheng, J.T. Silymarin inhibits cervical cancer cell through an increase of phosphatase and tensin homolog. Phytother. Res., 2012, 26(5), 709-715.
[http://dx.doi.org/10.1002/ptr.3618] [PMID: 22016029]
[54]
Wu, T.; Liu, W.; Guo, W.; Zhu, X. Silymarin suppressed lung cancer growth in mice via inhibiting myeloid-derived suppressor cells. Biomed. Pharmacother., 2016, 81, 460-467.
[http://dx.doi.org/10.1016/j.biopha.2016.04.039] [PMID: 27261626]
[55]
Kim, S.H.; Choo, G.S.; Yoo, E.S.; Woo, J.S.; Lee, J.H.; Han, S.H.; Jung, S.H.; Kim, H.J.; Jung, J.Y. Silymarin inhibits proliferation of human breast cancer cells via regulation of the MAPK signaling pathway and induction of apoptosis. Oncol. Lett., 2021, 21(6), 492.
[http://dx.doi.org/10.3892/ol.2021.12753] [PMID: 33968208]
[56]
Féher, J.; Lengyel, G. Silymarin in the prevention and treatment of liver diseases and primary liver cancer. Curr. Pharm. Biotechnol., 2012, 13(1), 210-217.
[http://dx.doi.org/10.2174/138920112798868818] [PMID: 21466434]
[57]
Koltai, T.; Fliegel, L. Role of silymarin in cancer treatment: Facts, hypotheses, and questions. J. Evid. Based Integr. Med., 2022, 27, 2515690x211068826.
[58]
Singh, R.P.; Agarwal, R. Flavonoid antioxidant silymarin and skin cancer. Antioxid. Redox Signal., 2002, 4(4), 655-663.
[http://dx.doi.org/10.1089/15230860260220166] [PMID: 12230878]
[59]
Zhu, W.; Zhang, J.S.; Young, C.Y. Silymarin inhibits function of the androgen receptor by reducing nuclear localization of the receptor in the human prostate cancer cell line LNCaP. Carcinogenesis, 2001, 22(9), 1399-1403.
[http://dx.doi.org/10.1093/carcin/22.9.1399] [PMID: 11532861]
[60]
Moher, D; Liberati, A; Tetzlaff, J; Altman, DG Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. Ann. Intern. Med., 2009, 151(4), 264-9, w64.
[61]
Nambiar, D.K.; Rajamani, P.; Deep, G.; Jain, A.K.; Agarwal, R.; Singh, R.P. Silibinin preferentially radiosensitizes prostate cancer by inhibiting DNA repair signaling. Mol. Cancer Ther., 2015, 14(12), 2722-2734.
[http://dx.doi.org/10.1158/1535-7163.MCT-15-0348] [PMID: 26516160]
[62]
Nambiar, D.K.; Rajamani, P.; Singh, R.P. Silibinin attenuates ionizing radiation-induced pro-angiogenic response and EMT in prostate cancer cells. Biochem. Biophys. Res. Commun., 2015, 456(1), 262-268.
[http://dx.doi.org/10.1016/j.bbrc.2014.11.069] [PMID: 25446081]
[63]
Lal, M.; Gupta, D. Studies on radiation sensitization efficacy by silymarin in colon carcinoma cells. Discoveries, 2016, 4(1), e56.
[http://dx.doi.org/10.15190/d.2016.3] [PMID: 32309577]
[64]
Prack Mc Cormick, B.; Langle, Y.; Belgorosky, D.; Vanzulli, S.; Balarino, N.; Sandes, E.; Eiján, A.M. Flavonoid silybin improves the response to radiotherapy in invasive bladder cancer. J. Cell. Biochem., 2018, 119(7), 5402-5412.
[http://dx.doi.org/10.1002/jcb.26693] [PMID: 29363820]
[65]
Bilgic, E.; Tuncel, N.; Koca, T. Radio-sensitivity on MCF-7 cells of silver nanoparticles synthesized by Silybum marianum; Inorgan Nano-Met Chem, 2021, pp. 1-9.
[66]
Rajput, M.; Mishra, D.; Kumar, K.; Singh, R.P. Silibinin radiosensitizes egf receptor-knockdown prostate cancer cells by attenuating DNA repair pathways. J. Cancer Prev., 2022, 27(3), 170-181.
[http://dx.doi.org/10.15430/JCP.2022.27.3.170] [PMID: 36258717]
[67]
Lal, M.; Ahmad Khan, S.; Gupta, D. Silymarin mediates apoptosis through activation of jnk/erk signaling pathway in human colon carcinoma cells in response to ( 60 Co) gamma radiation. Acta Scientific Cancer Biology, 2022, 6(6), 01-13.
[http://dx.doi.org/10.31080/ASCB.2022.06.0388]
[68]
Latacela, G.A.; Ramaiah, P.; Patra, I.; Jalil, A.T.; Gupta, R.; Madaminov, F.A.; Shaker Shafik, S.; Al-Gazally, M.E.; Ansari, M.J.; Kandeel, M.; Mustafa, Y.F.; Farhood, B. The radioprotective potentials of silymarin/silibinin against radiotherapy- induced toxicities: A systematic review of clinical and experimental studies. Curr. Med. Chem., 2023, 30(33), 3775-3797.
[http://dx.doi.org/10.2174/0929867330666221124155339] [PMID: 36424777]
[69]
Ghodousi, M.; Karbasforooshan, H.; Arabi, L.; Elyasi, S. Silymarin as a preventive or therapeutic measure for chemotherapy and radiotherapy-induced adverse reactions: A comprehensive review of preclinical and clinical data. Eur. J. Clin. Pharmacol., 2023, 79(1), 15-38.
[http://dx.doi.org/10.1007/s00228-022-03434-8] [PMID: 36450892]
[70]
Ramadan, L.A.; Roushdy, H.M.; Abu Senna, G.M.; Amin, N.E.; El-Deshw, O.A. Radioprotective effect of silymarin against radiation induced hepatotoxicity. Pharmacol. Res., 2002, 45(6), 447-454.
[http://dx.doi.org/10.1006/phrs.2002.0990] [PMID: 12162944]
[71]
Tiwari, P.; Kumar, A.; Ali, M.; Mishra, K.P. Radioprotection of plasmid and cellular DNA and Swiss mice by silibinin. Mutat. Res. Genet. Toxicol. Environ. Mutagen., 2010, 695(1-2), 55-60.
[http://dx.doi.org/10.1016/j.mrgentox.2009.11.007] [PMID: 19945544]
[72]
Becker-Schiebe, M.; Mengs, U.; Schaefer, M.; Bulitta, M.; Hoffmann, W. Topical use of a silymarin-based preparation to prevent radiodermatitis : Results of a prospective study in breast cancer patients. Strahlenther. Onkol., 2011, 187(8), 485-491.
[http://dx.doi.org/10.1007/s00066-011-2204-z] [PMID: 21786113]
[73]
Son, Y.; Lee, H.J.; Rho, J.K.; Chung, S.Y.; Lee, C.G.; Yang, K.; Kim, S.H.; Lee, M.; Shin, I.S.; Kim, J.S. The ameliorative effect of silibinin against radiation-induced lung injury: Protection of normal tissue without decreasing therapeutic efficacy in lung cancer. BMC Pulm. Med., 2015, 15(1), 68.
[http://dx.doi.org/10.1186/s12890-015-0055-6] [PMID: 26143275]
[74]
Adhikari, M.; Arora, R. The flavonolignan-silymarin protects enzymatic, hematological, and immune system against γ-radiation-induced toxicity. Environ. Toxicol., 2016, 31(6), 641-654.
[http://dx.doi.org/10.1002/tox.22076] [PMID: 25411116]
[75]
Kim, J.S.; Han, N.K.; Kim, S.H.; Lee, H.J. Silibinin attenuates radiation-induced intestinal fibrosis and reverses epithelial-to-mesenchymal transition. Oncotarget, 2017, 8(41), 69386-69397.
[http://dx.doi.org/10.18632/oncotarget.20624] [PMID: 29050211]
[76]
Elyasi, S.; Hosseini, S.; Niazi Moghadam, M.R.; Aledavood, S.A.; Karimi, G. Effect of oral silymarin administration on prevention of radiotherapy induced mucositis: A randomized, double-blinded, placebo-controlled clinical trial. Phytother. Res., 2016, 30(11), 1879-1885.
[http://dx.doi.org/10.1002/ptr.5704] [PMID: 27555604]
[77]
Fatehi, D.; Mohammadi, M.; Shekarchi, B.; Shabani, A.; Seify, M.; Rostamzadeh, A. Radioprotective effects of Silymarin on the sperm parameters of NMRI mice irradiated with γ-rays. J. Photochem. Photobiol. B, 2018, 178, 489-495.
[http://dx.doi.org/10.1016/j.jphotobiol.2017.12.004] [PMID: 29232573]
[78]
Karbasforooshan, H.; Hosseini, S.; Elyasi, S.; Fani Pakdel, A.; Karimi, G. Topical silymarin administration for prevention of acute radiodermatitis in breast cancer patients: A randomized, double-blind, placebo-controlled clinical trial. Phytother. Res., 2019, 33(2), 379-386.
[http://dx.doi.org/10.1002/ptr.6231] [PMID: 30479044]
[79]
Mohamed, M.A.E.H.; Mohammed, H.S.; Mostafa, S.A.; Ibrahim, M.T. Protective effects of Saraca indica L. leaves extract (family Fabaceae) against gamma irradiation induced injury in the kidney of female albino rats. Environ. Toxicol., 2021, 36(4), 506-519.
[http://dx.doi.org/10.1002/tox.23056] [PMID: 33166054]
[80]
Dheeraj, A.; Tailor, D.; Singh, S.P.; Singh, R.P. Anticancer attributes of silibinin: Chemo-and radiosensitization of cancer. In: Role of Nutraceuticals in Cancer Chemosensitization; Elsevier, 2018; pp. 199-220.
[81]
Wang, J.; Wang, H.; Qian, H. Biological effects of radiation on cancer cells. Mil. Med. Res., 2018, 5(1), 20.
[http://dx.doi.org/10.1186/s40779-018-0167-4] [PMID: 29958545]
[82]
Ashrafizadeh, M.; Farhood, B.; Eleojo Musa, A.; Taeb, S.; Najafi, M. The interactions and communications in tumor resistance to radiotherapy: Therapy perspectives. Int. Immunopharmacol., 2020, 87, 106807.
[http://dx.doi.org/10.1016/j.intimp.2020.106807] [PMID: 32683299]
[83]
Iliakis, G.; Wang, Y.; Guan, J.; Wang, H. DNA damage checkpoint control in cells exposed to ionizing radiation. Oncogene, 2003, 22(37), 5834-5847.
[http://dx.doi.org/10.1038/sj.onc.1206682] [PMID: 12947390]
[84]
Prise, K.M.; Schettino, G.; Folkard, M.; Held, K.D. New insights on cell death from radiation exposure. Lancet Oncol., 2005, 6(7), 520-528.
[http://dx.doi.org/10.1016/S1470-2045(05)70246-1] [PMID: 15992701]
[85]
Lee, S.Y.; Jeong, E.K.; Ju, M.K.; Jeon, H.M.; Kim, M.Y.; Kim, C.H.; Park, H.G.; Han, S.I.; Kang, H.S. Induction of metastasis, cancer stem cell phenotype, and oncogenic metabolism in cancer cells by ionizing radiation. Mol. Cancer, 2017, 16(1), 10.
[http://dx.doi.org/10.1186/s12943-016-0577-4] [PMID: 28137309]
[86]
Cheung, C.W.; Vesey, D.A.; Nicol, D.L.; Johnson, D.W. Silibinin inhibits renal cell carcinoma via mechanisms that are independent of insulin-like growth factor-binding protein 3. BJU Int., 2007, 99(2), 454-460.
[http://dx.doi.org/10.1111/j.1464-410X.2007.06571.x] [PMID: 17313429]
[87]
Bhatia, N.; Zhao, J.; Wolf, D.M.; Agarwal, R. Inhibition of human carcinoma cell growth and DNA synthesis by silibinin, an active constituent of milk thistle: Comparison with silymarin. Cancer Lett., 1999, 147(1-2), 77-84.
[http://dx.doi.org/10.1016/S0304-3835(99)00276-1] [PMID: 10660092]
[88]
Cui, H.; Li, T.L.; Guo, H.F.; Wang, J.L.; Xue, P.; Zhang, Y.; Fan, J.H.; Li, Z.P.; Gao, Y.J. Silymarin-mediated regulation of the cell cycle and DNA damage response exerts antitumor activity in human hepatocellular carcinoma. Oncol. Lett., 2018, 15(1), 885-892.
[PMID: 29399153]
[89]
Yurtcu, E.; İşeri, Ö.D.; Sahin, F.I. Genotoxic and cytotoxic effects of doxorubicin and silymarin on human hepatocellular carcinoma cells. Hum. Exp. Toxicol., 2014, 33(12), 1269-1276.
[http://dx.doi.org/10.1177/0960327114529453] [PMID: 24677352]
[90]
Deep, G.; Singh, R.P.; Agarwal, C.; Kroll, D.J.; Agarwal, R. Silymarin and silibinin cause G1 and G2–M cell cycle arrest via distinct circuitries in human prostate cancer PC3 cells: A comparison of flavanone silibinin with flavanolignan mixture silymarin. Oncogene, 2006, 25(7), 1053-1069.
[http://dx.doi.org/10.1038/sj.onc.1209146] [PMID: 16205633]
[91]
Ashrafizadeh, M.; Taeb, S.; Haghi-Aminjan, H.; Afrashi, S.; Moloudi, K.; Musa, A.E.; Najafi, M.; Farhood, B. Resveratrol as an enhancer of apoptosis in cancer: A mechanistic review. Anticancer. Agents Med. Chem., 2021, 21(17), 2327-2336.
[http://dx.doi.org/10.2174/1871520620666201020160348] [PMID: 33081687]
[92]
Mortezaee, K.; Najafi, M.; Farhood, B.; Ahmadi, A.; Potes, Y.; Shabeeb, D.; Musa, A.E. Modulation of apoptosis by melatonin for improving cancer treatment efficiency: An updated review. Life Sci., 2019, 228, 228-241.
[http://dx.doi.org/10.1016/j.lfs.2019.05.009] [PMID: 31077716]
[93]
Jang, J.S.; Kim, K.M.; Kang, K.H.; Choi, J.E.; Lee, W.K.; Kim, C.H.; Kang, Y.M.; Kam, S.; Kim, I.S.; Jun, J.E.; Jung, T.H.; Park, J.Y. Polymorphisms in the survivin gene and the risk of lung cancer. Lung Cancer, 2008, 60(1), 31-39.
[http://dx.doi.org/10.1016/j.lungcan.2007.09.008] [PMID: 17961802]
[94]
Akbari-Kordkheyli, V; Abbaszadeh-Goudarzi, K; Nejati-Laskokalayeh, M; Zarpou, S; Khonakdar-Tarsi, A The protective effects of silymarin on ischemia-reperfusion injuries: A mechanistic review. Iran J Basic Med Sci., 2019, 22(9), 968.
[95]
Fischer, T.W.; Zmijewski, M.A.; Wortsman, J.; Slominski, A. Melatonin maintains mitochondrial membrane potential and attenuates activation of initiator (casp-9) and effector caspases (casp-3/casp-7) and PARP in UVR-exposed HaCaT keratinocytes. J. Pineal Res., 2008, 44(4), 397-407.
[http://dx.doi.org/10.1111/j.1600-079X.2007.00542.x] [PMID: 18086147]
[96]
Moutabian, H.; Majdaeen, M.; Ghahramani-Asl, R.; Yadollahi, M.; Gharepapagh, E.; Ataei, G.; Falahatpour, Z.; Bagheri, H.; Farhood, B. A systematic review of the therapeutic effects of resveratrol in combination with 5-fluorouracil during colorectal cancer treatment: with a special focus on the oxidant, apoptotic, and anti-inflammatory activities. Cancer Cell Int., 2022, 22(1), 142.
[http://dx.doi.org/10.1186/s12935-022-02561-7] [PMID: 35366874]
[97]
Wu, X-Y.; Zhai, J.; Huan, X-K.; Xu, W-W.; Tian, J.; Farhood, B. A systematic review of the therapeutic potential of resveratrol during colorectal cancer chemotherapy. Mini Rev. Med. Chem., 2022.
[PMID: 36173048]
[98]
Santivasi, W.L.; Xia, F. Ionizing radiation-induced DNA damage, response, and repair. Antioxid. Redox Signal., 2014, 21(2), 251-259.
[http://dx.doi.org/10.1089/ars.2013.5668] [PMID: 24180216]
[99]
Surova, O.; Zhivotovsky, B. Various modes of cell death induced by DNA damage. Oncogene, 2013, 32(33), 3789-3797.
[http://dx.doi.org/10.1038/onc.2012.556] [PMID: 23208502]
[100]
Gudkov, A.V.; Komarova, E.A. The role of p53 in determining sensitivity to radiotherapy. Nat. Rev. Cancer, 2003, 3(2), 117-129.
[http://dx.doi.org/10.1038/nrc992] [PMID: 12563311]
[101]
Fei, P.; El-Deiry, W.S. P53 and radiation responses. Oncogene, 2003, 22(37), 5774-5783.
[http://dx.doi.org/10.1038/sj.onc.1206677] [PMID: 12947385]
[102]
Adhya, AK; Srinivasan, R; Patel, FD Radiation therapy induced changes in apoptosis and its major regulatory proteins, Bcl-2, Bcl-XL, and Bax, in locally advanced invasive squamous cell carcinoma of the cervix. Int. J. Gynecol. Pathol., 2006, 25(3), 281-287.
[103]
Sakakura, C.; Sweeney, E.A.; Shirahama, T.; Igarashi, Y.; Hakomori, S.; Nakatani, H.; Tsujimoto, H.; Imanishi, T.; Ohgaki, M.; Ohyama, T.; Yamazaki, J.; Hagiwara, A.; Yamaguchi, T.; Sawai, K.; Takahashi, T. Overexpression of bax sensitizes human breast cancer MCF-7 cells to radiation-induced apoptosis. Int. J. Cancer, 1996, 67(1), 101-105.
[http://dx.doi.org/10.1002/(SICI)1097-0215(19960703)67:1<101::AID-IJC17>3.0.CO;2-H] [PMID: 8690508]
[104]
Jänicke, R.U.; Sprengart, M.L.; Wati, M.R.; Porter, A.G. Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis. J. Biol. Chem., 1998, 273(16), 9357-9360.
[http://dx.doi.org/10.1074/jbc.273.16.9357] [PMID: 9545256]
[105]
Gondo, H.K. The effect of spirulina on apoptosis through the caspase-3 pathway in a Preeclamptic Wistar rat model. J. Nat. Sci. Biol. Med., 2021, 12(3), 280-284.
[106]
Yardım, A.; Kucukler, S.; Özdemir, S.; Çomaklı, S.; Caglayan, C.; Kandemir, F.M.; Çelik, H. Silymarin alleviates docetaxel-induced central and peripheral neurotoxicity by reducing oxidative stress, inflammation and apoptosis in rats. Gene, 2021, 769, 145239.
[http://dx.doi.org/10.1016/j.gene.2020.145239] [PMID: 33069805]
[107]
Su, C. Survivin in survival of hepatocellular carcinoma. Cancer Lett., 2016, 379(2), 184-190.
[http://dx.doi.org/10.1016/j.canlet.2015.06.016] [PMID: 26118774]
[108]
Rödel, F.; Hoffmann, J.; Distel, L.; Herrmann, M.; Noisternig, T.; Papadopoulos, T.; Sauer, R.; Rödel, C. Survivin as a radioresistance factor, and prognostic and therapeutic target for radiotherapy in rectal cancer. Cancer Res., 2005, 65(11), 4881-4887.
[http://dx.doi.org/10.1158/0008-5472.CAN-04-3028] [PMID: 15930309]
[109]
Mobahat, M.; Narendran, A.; Riabowol, K. Survivin as a preferential target for cancer therapy. Int. J. Mol. Sci., 2014, 15(2), 2494-2516.
[http://dx.doi.org/10.3390/ijms15022494] [PMID: 24531137]
[110]
Vaid, M.; Singh, T.; Prasad, R.; Katiyar, S.K. Silymarin inhibits melanoma cell growth both in vitro and in vivo by targeting cell cycle regulators, angiogenic biomarkers and induction of apoptosis. Mol. Carcinog., 2015, 54(11), 1328-1339.
[http://dx.doi.org/10.1002/mc.22208] [PMID: 25174976]
[111]
Fan, L.; Ma, Y.; Liu, Y.; Zheng, D.; Huang, G. Silymarin induces cell cycle arrest and apoptosis in ovarian cancer cells. Eur. J. Pharmacol., 2014, 743, 79-88.
[http://dx.doi.org/10.1016/j.ejphar.2014.09.019] [PMID: 25242120]
[112]
Kim, K.W.; Choi, C.H.; Kim, T.H.; Kwon, C.H.; Woo, J.S.; Kim, Y.K. Silibinin inhibits glioma cell proliferation via Ca2+/ROS/MAPK-dependent mechanism in vitro and glioma tumor growth in vivo. Neurochem. Res., 2009, 34(8), 1479-1490.
[http://dx.doi.org/10.1007/s11064-009-9935-6] [PMID: 19263218]
[113]
Singh, R.P.; Raina, K.; Sharma, G.; Agarwal, R. Silibinin inhibits established prostate tumor growth, progression, invasion, and metastasis and suppresses tumor angiogenesis and epithelial-mesenchymal transition in transgenic adenocarcinoma of the mouse prostate model mice. Clin. Cancer Res., 2008, 14(23), 7773-7780.
[http://dx.doi.org/10.1158/1078-0432.CCR-08-1309] [PMID: 19047104]
[114]
Wang, Y.X.; Cai, H.; Jiang, G.; Zhou, T.B.; Wu, H. Silibinin inhibits proliferation, induces apoptosis and causes cell cycle arrest in human gastric cancer MGC803 cells via STAT3 pathway inhibition. Asian Pac. J. Cancer Prev., 2014, 15(16), 6791-6798.
[http://dx.doi.org/10.7314/APJCP.2014.15.16.6791] [PMID: 25169527]
[115]
Won, D.H.; Kim, L.H.; Jang, B.; Yang, I.H.; Kwon, H.J.; Jin, B.; Oh, S.H.; Kang, J.H.; Hong, S.D.; Shin, J.A.; Cho, S.D. In vitro and in vivo anti-cancer activity of silymarin on oral cancer. Tumour Biol., 2018, 40(5)
[http://dx.doi.org/10.1177/1010428318776170] [PMID: 29764340]
[116]
Nambiar, D.; Prajapati, V.; Agarwal, R.; Singh, R.P. In vitro and in vivo anticancer efficacy of silibinin against human pancreatic cancer BxPC-3 and PANC-1 cells. Cancer Lett., 2013, 334(1), 109-117.
[http://dx.doi.org/10.1016/j.canlet.2012.09.004] [PMID: 23022268]
[117]
Wang, Y.; Yuan, A.J.; Wu, Y.J.; Wu, L.M.; Zhang, L. Silymarin in cancer therapy: Mechanisms of action, protective roles in chemotherapy-induced toxicity, and nanoformulations. J. Funct. Foods, 2023, 100, 105384.
[http://dx.doi.org/10.1016/j.jff.2022.105384]
[118]
Mashhadi, A.B.M.; Mashhadi, A.B.M.; Golmohammad, S. Overview of Silibinin anti-tumor effects. J. Herb. Med., 2020, 23, 100375.
[http://dx.doi.org/10.1016/j.hermed.2020.100375]
[119]
Shi, W; Hou, X; Bao, X; Hou, W; Jiang, X; Ma, L Mechanism and protection of radiotherapy induced sensorineural hearing loss for head and neck cancer. Biomed Res Int., 2021, 2021, 3548706.
[http://dx.doi.org/10.1155/2021/3548706]
[120]
Brown, L.; Benchimol, S. The involvement of MAPK signaling pathways in determining the cellular response to p53 activation: cell cycle arrest or apoptosis. J. Biol. Chem., 2006, 281(7), 3832-3840.
[http://dx.doi.org/10.1074/jbc.M507951200] [PMID: 16330547]
[121]
Hariyanti, T.; Margiana, R.; Al-Gazally, M.E.; Patra, I.; Lateef Al-Awsi, G.R.; Hameed, N.; Kayumova, D.; Ansari, M.J.; Torres-Criollo, L.M.; Mustafa, Y.F.; Abedi-Firouzjah, R.; Farhood, B. The protective effects of silymarin on the reproductive toxicity: A comprehensive review. Curr. Med. Chem., 2023, 30(39), 4421-4449.
[http://dx.doi.org/10.2174/0929867330666230130115332] [PMID: 36717999]
[122]
Hoxhaj, G.; Manning, B.D. The PI3K–AKT network at the interface of oncogenic signalling and cancer metabolism. Nat. Rev. Cancer, 2020, 20(2), 74-88.
[http://dx.doi.org/10.1038/s41568-019-0216-7] [PMID: 31686003]
[123]
Li, H.F.; Kim, J.S.; Waldman, T. Radiation-induced Akt activation modulates radioresistance in human glioblastoma cells. Radiat. Oncol., 2009, 4(1), 43.
[http://dx.doi.org/10.1186/1748-717X-4-43] [PMID: 19828040]
[124]
Hein, A.L.; Ouellette, M.M.; Yan, Y. Radiation-induced signaling pathways that promote cancer cell survival (Review). Int. J. Oncol., 2014, 45(5), 1813-1819.
[http://dx.doi.org/10.3892/ijo.2014.2614] [PMID: 25174607]
[125]
Marampon, F.; Ciccarelli, C.; Zani, B.M. Biological rationale for targeting MEK/ERK pathways in anti-cancer therapy and to potentiate tumour responses to radiation. Int. J. Mol. Sci., 2019, 20(10), 2530.
[http://dx.doi.org/10.3390/ijms20102530] [PMID: 31126017]
[126]
Lee, K.B.; Kim, K-R.; Huh, T-L.; Lee, Y.M. Proton induces apoptosis of hypoxic tumor cells by the p53-dependent and p38/JNK MAPK signaling pathways. Int. J. Oncol., 2008, 33(6), 1247-1256.
[PMID: 19020758]
[127]
Choi, E.S.; Oh, S.; Jang, B.; Yu, H.J.; Shin, J.A.; Cho, N.P.; Yang, I.H.; Won, D.H.; Kwon, H.J.; Hong, S.D.; Cho, S.D. Silymarin and its active component silibinin act as novel therapeutic alternatives for salivary gland cancer by targeting the ERK1/2-Bim signaling cascade. Cell Oncol., 2017, 40(3), 235-246.
[http://dx.doi.org/10.1007/s13402-017-0318-8] [PMID: 28401485]
[128]
Singh, R.P.; Dhanalakshmi, S.; Mohan, S.; Agarwal, C.; Agarwal, R. Silibinin inhibits UVB- and epidermal growth factor–induced mitogenic and cell survival signaling involving activator protein-1 and nuclear factor-κB in mouse epidermal JB6 cells. Mol. Cancer Ther., 2006, 5(5), 1145-1153.
[http://dx.doi.org/10.1158/1535-7163.MCT-05-0478] [PMID: 16731746]
[129]
Bowman, T.; Garcia, R.; Turkson, J.; Jove, R. STATs in oncogenesis. Oncogene, 2000, 19(21), 2474-2488.
[http://dx.doi.org/10.1038/sj.onc.1203527] [PMID: 10851046]
[130]
Bromberg, J.F. Activation of STAT proteins and growth control. BioEssays, 2001, 23(2), 161-169.
[http://dx.doi.org/10.1002/1521-1878(200102)23:2<161::AID-BIES1023>3.0.CO;2-0] [PMID: 11169589]
[131]
Bromberg, J. Stat proteins and oncogenesis. J. Clin. Invest., 2002, 109(9), 1139-1142.
[http://dx.doi.org/10.1172/JCI0215617] [PMID: 11994401]
[132]
Epling-Burnette, P.K.; Liu, J.H.; Catlett-Falcone, R.; Turkson, J.; Oshiro, M.; Kothapalli, R.; Li, Y.; Wang, J.M.; Yang-Yen, H.F.; Karras, J.; Jove, R.; Loughran, T.P., Jr Inhibition of STAT3 signaling leads to apoptosis of leukemic large granular lymphocytes and decreased Mcl-1 expression. J. Clin. Invest., 2001, 107(3), 351-362.
[http://dx.doi.org/10.1172/JCI9940] [PMID: 11160159]
[133]
Yu, H.; Jove, R. The STATs of cancer — new molecular targets come of age. Nat. Rev. Cancer, 2004, 4(2), 97-105.
[http://dx.doi.org/10.1038/nrc1275] [PMID: 14964307]
[134]
Park, S.Y.; Lee, C.J.; Choi, J.H.; Kim, J.H.; Kim, J.W.; Kim, J.Y.; Nam, J.S. The JAK2/STAT3/CCND2 Axis promotes colorectal cancer stem cell persistence and radioresistance. J. Exp. Clin. Cancer Res., 2019, 38(1), 399.
[http://dx.doi.org/10.1186/s13046-019-1405-7] [PMID: 31511084]
[135]
Lu, L.; Dong, J.; Wang, L.; Xia, Q.; Zhang, D.; Kim, H.; Yin, T.; Fan, S.; Shen, Q. Activation of STAT3 and Bcl-2 and reduction of reactive oxygen species (ROS) promote radioresistance in breast cancer and overcome of radioresistance with niclosamide. Oncogene, 2018, 37(39), 5292-5304.
[http://dx.doi.org/10.1038/s41388-018-0340-y] [PMID: 29855616]
[136]
Li, F.; Gao, L.; Wang, Z.; Dong, B.; Yan, T.; Jiang, Q.; Chen, X. Radiation enhances the invasion abilities of pulmonary adenocarcinoma cells via STAT3. Mol. Med. Rep., 2013, 7(6), 1883-1888.
[http://dx.doi.org/10.3892/mmr.2013.1441] [PMID: 23620191]
[137]
Singh-Gupta, V.; Zhang, H.; Banerjee, S.; Kong, D.; Raffoul, J.J.; Sarkar, F.H.; Hillman, G.G. Radiation-induced HIF-1α cell survival pathway is inhibited by soy isoflavones in prostate cancer cells. Int. J. Cancer, 2009, 124(7), 1675-1684.
[http://dx.doi.org/10.1002/ijc.24015] [PMID: 19101986]
[138]
Wang, X.; Zhang, X.; Qiu, C.; Yang, N. STAT3 contributes to radioresistance in cancer. Front. Oncol., 2020, 10, 1120.
[http://dx.doi.org/10.3389/fonc.2020.01120] [PMID: 32733808]
[139]
Gaur, P.; Bose, D.; Samuel, S.; Ellis, L.M. Eds.; Targeting tumor angiogenesis. In: Seminars in oncology; Elsevier, 2009.
[140]
Kanthou, C.; Tozer, G. Targeting the vasculature of tumours: Combining VEGF pathway inhibitors with radiotherapy. Br. J. Radiol., 2019, 92(1093), 20180405.
[PMID: 30160184]
[141]
Bachtiary, B.; Selzer, E.; Knocke, T.H.; Pötter, R.; Obermair, A. Serum VEGF levels in patients undergoing primary radiotherapy for cervical cancer: impact on progression-free survival. Cancer Lett., 2002, 179(2), 197-203.
[http://dx.doi.org/10.1016/S0304-3835(01)00872-2] [PMID: 11888674]
[142]
Chen, HH; Su, W-C; Chou, C-Y; Guo, H-R; Ho, S-Y; Que, J Increased expression of nitric oxide synthase and cyclooxygenase-2 is associated with poor survival in cervical cancer treated with radiotherapy. Int. J. Radiat. Oncol Biol. Phys., 2005, 63(4), 1093-100.
[http://dx.doi.org/10.1016/j.ijrobp.2005.03.062]
[143]
Solberg, TD; Nearman, J; Mullins, J; Li, S; Baranowska-Kortylewicz, J Correlation between tumor growth delay and expression of cancer and host VEGF, VEGFR2, and osteopontin in response to radiotherapy. Int. J. Radiat. Oncol. Biol. Phys., 2008, 72(3), 918-926.
[144]
Kleibeuker, E.A.; Griffioen, A.W.; Verheul, H.M.; Slotman, B.J.; Thijssen, V.L. Combining angiogenesis inhibition and radiotherapy: A double-edged sword. Drug Resist. Updat., 2012, 15(3), 173-182.
[http://dx.doi.org/10.1016/j.drup.2012.04.002] [PMID: 22561672]
[145]
Sonveaux, P.; Brouet, A.; Havaux, X.; Grégoire, V.; Dessy, C.; Balligand, J-L.; Feron, O. Irradiation-induced angiogenesis through the up-regulation of the nitric oxide pathway: Implications for tumor radiotherapy. Cancer Res., 2003, 63(5), 1012-1019.
[PMID: 12615716]
[146]
Deep, G.; Gangar, S.C.; Rajamanickam, S.; Raina, K.; Gu, M.; Agarwal, C.; Oberlies, N.H.; Agarwal, R. Angiopreventive efficacy of pure flavonolignans from milk thistle extract against prostate cancer: Targeting VEGF-VEGFR signaling. PLoS One, 2012, 7(4), e34630.
[http://dx.doi.org/10.1371/journal.pone.0034630] [PMID: 22514647]
[147]
Deep, G.; Raina, K.; Singh, R.P.; Oberlies, N.H.; Kroll, D.J.; Agarwal, R. Isosilibinin inhibits advanced human prostate cancer growth in athymic nude mice: Comparison with silymarin and silibinin. Int. J. Cancer, 2008, 123(12), 2750-2758.
[http://dx.doi.org/10.1002/ijc.23879] [PMID: 18798272]
[148]
Singh, R.P.; Sharma, G.; Dhanalakshmi, S.; Agarwal, C.; Agarwal, R. Suppression of advanced human prostate tumor growth in athymic mice by silibinin feeding is associated with reduced cell proliferation, increased apoptosis, and inhibition of angiogenesis. Cancer Epidemiol. Biomarkers Prev., 2003, 12(9), 933-939.
[PMID: 14504208]
[149]
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]
[150]
Singh, R.P.; Deep, G.; Chittezhath, M.; Kaur, M.; Dwyer-Nield, L.D.; Malkinson, A.M.; Agarwal, R. Effect of silibinin on the growth and progression of primary lung tumors in mice. J. Natl. Cancer Inst., 2006, 98(12), 846-855.
[http://dx.doi.org/10.1093/jnci/djj231] [PMID: 16788158]
[151]
Ramasamy, K.; Dwyer-Nield, L.D.; Serkova, N.J.; Hasebroock, K.M.; Tyagi, A.; Raina, K.; Singh, R.P.; Malkinson, A.M.; Agarwal, R. Silibinin prevents lung tumorigenesis in wild-type but not in iNOS-/- mice: potential of real-time micro-CT in lung cancer chemoprevention studies. Clin. Cancer Res., 2011, 17(4), 753-761.
[http://dx.doi.org/10.1158/1078-0432.CCR-10-2290] [PMID: 21148748]
[152]
Yang, S.H.; Lin, J.K.; Chen, W.S.; Chiu, J.H. Anti-angiogenic effect of silymarin on colon cancer lovo cell line. J. Surg. Res., 2003, 113(1), 133-138.
[http://dx.doi.org/10.1016/S0022-4804(03)00229-4] [PMID: 12943822]
[153]
García-Maceira, P.; Mateo, J. Silibinin inhibits hypoxia-inducible factor-1α and mTOR/p70S6K/4E-BP1 signalling pathway in human cervical and hepatoma cancer cells: implications for anticancer therapy. Oncogene, 2009, 28(3), 313-324.
[http://dx.doi.org/10.1038/onc.2008.398] [PMID: 18978810]
[154]
Miyazawa, M.; Yasuda, M.; Miyazawa, M.; Ogane, N.; Katoh, T.; Yano, M.; Hirasawa, T.; Mikami, M.; Ishimoto, H. Hypoxia-inducible factor-1α suppression in ovarian clear-cell carcinoma cells by silibinin administration. Anticancer Res., 2020, 40(12), 6791-6798.
[http://dx.doi.org/10.21873/anticanres.14702] [PMID: 33288572]
[155]
Tsai, J.H.; Yang, J. Epithelial–mesenchymal plasticity in carcinoma metastasis. Genes Dev., 2013, 27(20), 2192-2206.
[http://dx.doi.org/10.1101/gad.225334.113] [PMID: 24142872]
[156]
Weber, G.F. Why does cancer therapy lack effective anti-metastasis drugs? Cancer Lett., 2013, 328(2), 207-211.
[http://dx.doi.org/10.1016/j.canlet.2012.09.025] [PMID: 23059758]
[157]
Quail, D.F.; Joyce, J.A. Microenvironmental regulation of tumor progression and metastasis. Nat. Med., 2013, 19(11), 1423-1437.
[http://dx.doi.org/10.1038/nm.3394] [PMID: 24202395]
[158]
Wu, M.; Wang, G.; Hu, W.; Yao, Y.; Yu, X.F. Emerging roles and therapeutic value of exosomes in cancer metastasis. Mol. Cancer, 2019, 18(1), 53.
[http://dx.doi.org/10.1186/s12943-019-0964-8] [PMID: 30925925]
[159]
Bakir, B.; Chiarella, A.M.; Pitarresi, J.R.; Rustgi, A.K. EMT, MET, plasticity, and tumor metastasis. Trends Cell Biol., 2020, 30(10), 764-776.
[http://dx.doi.org/10.1016/j.tcb.2020.07.003] [PMID: 32800658]
[160]
Craene, B.D.; Berx, G. Regulatory networks defining EMT during cancer initiation and progression. Nat. Rev. Cancer, 2013, 13(2), 97-110.
[http://dx.doi.org/10.1038/nrc3447] [PMID: 23344542]
[161]
Lamouille, S.; Xu, J.; Derynck, R. Molecular mechanisms of epithelial–mesenchymal transition. Nat. Rev. Mol. Cell Biol., 2014, 15(3), 178-196.
[http://dx.doi.org/10.1038/nrm3758] [PMID: 24556840]
[162]
Wild-Bode, C.; Weller, M.; Rimner, A.; Dichgans, J.; Wick, W. Sublethal irradiation promotes migration and invasiveness of glioma cells: Implications for radiotherapy of human glioblastoma. Cancer Res., 2001, 61(6), 2744-2750.
[PMID: 11289157]
[163]
Kawamoto, A.; Yokoe, T.; Tanaka, K.; Saigusa, S.; Toiyama, Y.; Yasuda, H.; Inoue, Y.; Miki, C.; Kusunoki, M. Radiation induces epithelial-mesenchymal transition in colorectal cancer cells. Oncol. Rep., 2012, 27(1), 51-57.
[PMID: 21971767]
[164]
Zhang, X.; Li, X.; Zhang, N.; Yang, Q.; Moran, M.S. Low doses ionizing radiation enhances the invasiveness of breast cancer cells by inducing epithelial–mesenchymal transition. Biochem. Biophys. Res. Commun., 2011, 412(1), 188-192.
[http://dx.doi.org/10.1016/j.bbrc.2011.07.074] [PMID: 21810413]
[165]
Li, T.; Zeng, Z-C.; Wang, L.; Qiu, S-J.; Zhou, J-W.; Zhi, X-T.; Yu, H-H.; Tang, Z-Y. Radiation enhances long-term metastasis potential of residual hepatocellular carcinoma in nude mice through TMPRSS4-induced epithelial–mesenchymal transition. Cancer Gene Ther., 2011, 18(9), 617-626.
[http://dx.doi.org/10.1038/cgt.2011.29] [PMID: 21637307]
[166]
Vaid, M.; Prasad, R.; Sun, Q.; Katiyar, S.K. Silymarin targets β-catenin signaling in blocking migration/invasion of human melanoma cells. PLoS One, 2011, 6(7), e23000.
[http://dx.doi.org/10.1371/journal.pone.0023000] [PMID: 21829575]
[167]
Chu, S.C.; Chiou, H.L.; Chen, P.N.; Yang, S.F.; Hsieh, Y.S. Silibinin inhibits the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2. Mol. Carcinog., 2004, 40(3), 143-149.
[http://dx.doi.org/10.1002/mc.20018]
[168]
Singh, T.; Prasad, R.; Katiyar, S.K. Therapeutic intervention of silymarin on the migration of non-small cell lung cancer cells is associated with the axis of multiple molecular targets including class 1 HDACs, ZEB1 expression, and restoration of miR-203 and E-cadherin expression. Am. J. Cancer Res., 2016, 6(6), 1287-1301.
[PMID: 27429844]
[169]
Kim, D.H.; Park, S.J.; Lee, S.Y.; Yoon, H.S.; Park, C.M. Silymarin attenuates invasion and migration through the regulation of epithelial-mesenchymal transition in Huh7 cells. Korean J Clin Lab Sci, 2018, 50(3), 337-344.
[http://dx.doi.org/10.15324/kjcls.2018.50.3.337]
[170]
Raina, K.; Rajamanickam, S.; Singh, R.P.; Deep, G.; Chittezhath, M.; Agarwal, R. Stage-specific inhibitory effects and associated mechanisms of silibinin on tumor progression and metastasis in transgenic adenocarcinoma of the mouse prostate model. Cancer Res., 2008, 68(16), 6822-6830.
[http://dx.doi.org/10.1158/0008-5472.CAN-08-1332] [PMID: 18701508]
[171]
Ting, H.J.; Deep, G.; Jain, A.K.; Cimic, A.; Sirintrapun, J.; Romero, L.M.; Cramer, S.D.; Agarwal, C.; Agarwal, R. Silibinin prevents prostate cancer cell-mediated differentiation of naïve fibroblasts into cancer-associated fibroblast phenotype by targeting TGF β2. Mol. Carcinog., 2015, 54(9), 730-741.
[http://dx.doi.org/10.1002/mc.22135] [PMID: 24615813]
[172]
Wu, K.; Ning, Z.; Zeng, J.; Fan, J.; Zhou, J.; Zhang, T.; Zhang, L.; Chen, Y.; Gao, Y.; Wang, B.; Guo, P.; Li, L.; Wang, X.; He, D. Silibinin inhibits β-catenin/ZEB1 signaling and suppresses bladder cancer metastasis via dual-blocking epithelial–mesenchymal transition and stemness. Cell. Signal., 2013, 25(12), 2625-2633.
[http://dx.doi.org/10.1016/j.cellsig.2013.08.028] [PMID: 24012496]
[173]
Sameri, S.; Saidijam, M.; Bahreini, F.; Najafi, R. Cancer chemopreventive activities of silibinin on colorectal cancer through regulation of E-cadherin/β-catenin pathway. Nutr. Cancer, 2021, 73(8), 1389-1399.
[http://dx.doi.org/10.1080/01635581.2020.1800764] [PMID: 32748663]
[174]
Soleimani, V.; Delghandi, P.S.; Moallem, S.A.; Karimi, G. Safety and toxicity of silymarin, the major constituent of milk thistle extract: An updated review. Phytother. Res., 2019, 33(6), 1627-1638.
[http://dx.doi.org/10.1002/ptr.6361] [PMID: 31069872]
[175]
Bijak, M. Silybin, a major bioactive component of milk thistle (Silybum marianum L. Gaernt.)—chemistry, bioavailability, and metabolism. Molecules, 2017, 22(11), 1942.
[http://dx.doi.org/10.3390/molecules22111942] [PMID: 29125572]
[176]
Gillessen, A.; Schmidt, H.H.J. Silymarin as supportive treatment in liver diseases: A narrative review. Adv. Ther., 2020, 37(4), 1279-1301.
[http://dx.doi.org/10.1007/s12325-020-01251-y] [PMID: 32065376]
[177]
Amawi, H.; Hussein, N.A.; Karthikeyan, C.; Manivannan, E.; Wisner, A.; Williams, F.E.; Samuel, T.; Trivedi, P.; Ashby, C.R., Jr; Tiwari, A.K. HM015k, a novel silybin derivative, multi-targets metastatic ovarian cancer cells and is safe in zebrafish toxicity studies. Front. Pharmacol., 2017, 8, 498.
[http://dx.doi.org/10.3389/fphar.2017.00498] [PMID: 28824426]
[178]
Kosina, P.; Kren, V.; Gebhardt, R.; Grambal, F.; Ulrichová, J.; Walterová, D. Antioxidant properties of silybin glycosides. Phytother. Res., 2002, 16(S1), S33-S39.
[http://dx.doi.org/10.1002/ptr.796] [PMID: 11933137]
[179]
Dobiasová, S.; Řehořová, K.; Kučerová, D.; Biedermann, D.; Káňová, K.; Petrásková, L. Multidrug resistance modulation activity of silybin derivatives and their anti-inflammatory potential. Antioxidants, 2020, 9(5), 455.
[http://dx.doi.org/10.3390/antiox9050455]
[180]
Simánek, V.; Kubisch, J.; Sedmera, P.; Halada, P.; Gazák, R.; Skottová, N.; Kren, V. Chemoenzymatic preparation of oligoglycosides of silybin, the flavonolignan from Silybum marianum. Heterocycles, 2001, 54(2), 901-915.
[http://dx.doi.org/10.3987/COM-00-S(I)89]
[181]
Škottová, N.; ŠVagera, Z.; Večeřa, R.; Urbánek, K.; Jegorov, A.; Šimánek, V. Pharmacokinetic study of iodine-labeled silibinins in rat. Pharmacol. Res., 2001, 44(3), 247-253.
[http://dx.doi.org/10.1006/phrs.2001.0854] [PMID: 11529693]
[182]
Plíšková, M.; Vondráček, J.; Křen, V.; Gažák, R.; Sedmera, P.; Walterová, D.; Psotová, J.; Šimánek, V.; Machala, M. Effects of silymarin flavonolignans and synthetic silybin derivatives on estrogen and aryl hydrocarbon receptor activation. Toxicology, 2005, 215(1-2), 80-89.
[http://dx.doi.org/10.1016/j.tox.2005.06.020] [PMID: 16076518]
[183]
Roubalová, L.; Dinkova-Kostova, A.T.; Biedermann, D.; Křen, V.; Ulrichová, J.; Vrba, J. Flavonolignan 2,3-dehydrosilydianin activates Nrf2 and upregulates NAD(P)H:quinone oxidoreductase 1 in Hepa1c1c7 cells. Fitoterapia, 2017, 119, 115-120.
[http://dx.doi.org/10.1016/j.fitote.2017.04.012] [PMID: 28450126]
[184]
Pyszková, M.; Biler, M.; Biedermann, D.; Valentová, K.; Kuzma, M.; Vrba, J.; Ulrichová, J.; Sokolová, R.; Mojović, M.; Popović-Bijelić, A.; Kubala, M.; Trouillas, P.; Křen, V.; Vacek, J. Flavonolignan 2,3-dehydroderivatives: Preparation, antiradical and cytoprotective activity. Free Radic. Biol. Med., 2016, 90, 114-125.
[http://dx.doi.org/10.1016/j.freeradbiomed.2015.11.014] [PMID: 26582372]
[185]
Yang, L.X.; Huang, K.X.; Li, H.B.; Gong, J.X.; Wang, F.; Feng, Y.B.; Tao, Q.F.; Wu, Y.H.; Li, X.K.; Wu, X.M.; Zeng, S.; Spencer, S.; Zhao, Y.; Qu, J. Design, synthesis, and examination of neuron protective properties of alkenylated and amidated dehydro-silybin derivatives. J. Med. Chem., 2009, 52(23), 7732-7752.
[http://dx.doi.org/10.1021/jm900735p] [PMID: 19673490]
[186]
Mizuno, M.; Mori, K.; Tsuchiya, K.; Takaki, T.; Misawa, T.; Demizu, Y.; Shibanuma, M.; Fukuhara, K. Design, synthesis, and biological activity of conformationally restricted analogues of silibinin. ACS Omega, 2020, 5(36), 23164-23174.
[http://dx.doi.org/10.1021/acsomega.0c02936] [PMID: 32954167]
[187]
Zarrelli, A.; Romanucci, V.; Tuccillo, C.; Federico, A.; Loguercio, C.; Gravante, R.; Di Fabio, G. New silibinin glyco-conjugates: Synthesis and evaluation of antioxidant properties. Bioorg. Med. Chem. Lett., 2014, 24(22), 5147-5149.
[http://dx.doi.org/10.1016/j.bmcl.2014.10.023] [PMID: 25442301]
[188]
Vue, B.; Zhang, S.; Zhang, X.; Parisis, K.; Zhang, Q.; Zheng, S.; Wang, G.; Chen, Q.H. Silibinin derivatives as anti-prostate cancer agents: Synthesis and cell-based evaluations. Eur. J. Med. Chem., 2016, 109, 36-46.
[http://dx.doi.org/10.1016/j.ejmech.2015.12.041] [PMID: 26748997]
[189]
Rajnochová Svobodová, A.; Gabrielová, E.; Ulrichová, J.; Zálešák, B.; Biedermann, D.; Vostálová, J. A pilot study of the UVA-photoprotective potential of dehydrosilybin, isosilybin, silychristin, and silydianin on human dermal fibroblasts. Arch. Dermatol. Res., 2019, 311(6), 477-490.
[http://dx.doi.org/10.1007/s00403-019-01928-7] [PMID: 31079190]
[190]
Drouet, S.; Doussot, J.; Garros, L.; Mathiron, D.; Bassard, S.; Favre-Réguillon, A.; Molinié, R.; Lainé, É.; Hano, C. Selective synthesis of 3-O-Palmitoyl-Silybin, a New-to-Nature flavonolignan with increased protective action against oxidative damages in lipophilic media. Molecules, 2018, 23(10), 2594.
[http://dx.doi.org/10.3390/molecules23102594] [PMID: 30309022]
[191]
Chen, X.; Zenger, K.; Lupp, A.; Kling, B.; Heilmann, J.; Fleck, C.; Kraus, B.; Decker, M. Tacrine-silibinin codrug shows neuro- and hepatoprotective effects in vitro and pro-cognitive and hepatoprotective effects in vivo. J. Med. Chem., 2012, 55(11), 5231-5242.
[http://dx.doi.org/10.1021/jm300246n] [PMID: 22624880]
[192]
Tilley, C.; Deep, G.; Agarwal, C.; Wempe, M.F.; Biedermann, D.; Valentová, K.; Kren, V.; Agarwal, R. Silibinin and its 2,3-dehydro-derivative inhibit basal cell carcinoma growth via suppression of mitogenic signaling and transcription factors activation. Mol. Carcinog., 2016, 55(1), 3-14.
[http://dx.doi.org/10.1002/mc.22253] [PMID: 25492239]
[193]
Di Costanzo, A.; Angelico, R. Formulation strategies for enhancing the bioavailability of silymarin: The dtate of the art. Molecules, 2019, 24(11), 2155.
[http://dx.doi.org/10.3390/molecules24112155] [PMID: 31181687]
[194]
He, J.; Hou, S.; Lu, W.; Zhu, L.; Feng, J. Preparation, pharmacokinetics and body distribution of silymarin-loaded solid lipid nanoparticles after oral administration. J. Biomed. Nanotechnol., 2007, 3(2), 195-202.
[http://dx.doi.org/10.1166/jbn.2007.024]
[195]
Yousaf, A.M.; Malik, U.R.; Shahzad, Y.; Mahmood, T.; Hussain, T. Silymarin-laden PVP-PEG polymeric composite for enhanced aqueous solubility and dissolution rate: Preparation and in vitro characterization. J. Pharm. Anal., 2019, 9(1), 34-39.
[http://dx.doi.org/10.1016/j.jpha.2018.09.003] [PMID: 30740255]
[196]
Ibrahim, A.H.; Rosqvist, E.; Smått, J.H.; Ibrahim, H.M.; Ismael, H.R.; Afouna, M.I.; Samy, A.M.; Rosenholm, J.M. Formulation and optimization of lyophilized nanosuspension tablets to improve the physicochemical properties and provide immediate release of silymarin. Int. J. Pharm., 2019, 563, 217-227.
[http://dx.doi.org/10.1016/j.ijpharm.2019.03.064] [PMID: 30946894]
[197]
Liang, J.; Liu, Y.; Liu, J.; Li, Z.; Fan, Q.; Jiang, Z.; Yan, F.; Wang, Z.; Huang, P.; Feng, N. Chitosan-functionalized lipid-polymer hybrid nanoparticles for oral delivery of silymarin and enhanced lipid-lowering effect in NAFLD. J. Nanobiotechnology, 2018, 16(1), 64.
[http://dx.doi.org/10.1186/s12951-018-0391-9] [PMID: 30176941]
[198]
Yang, G.; Zhao, Y.; Feng, N.; Zhang, Y.; Liu, Y.; Dang, B. Improved dissolution and bioavailability of silymarin delivered by a solid dispersion prepared using supercritical fluids. Asian J. Pharm. Sci., 2015, 10(3), 194-202.
[http://dx.doi.org/10.1016/j.ajps.2014.12.001]
[199]
Nasr, S.S.; Nasra, M.M.A.; Hazzah, H.A.; Abdallah, O.Y. Mesoporous silica nanoparticles, a safe option for silymarin delivery: Preparation, characterization, and in vivo evaluation. Drug Deliv. Transl. Res., 2019, 9(5), 968-979.
[http://dx.doi.org/10.1007/s13346-019-00640-3] [PMID: 31001719]
[200]
Nagi, A.; Iqbal, B.; Kumar, S.; Sharma, S.; Ali, J.; Baboota, S. Quality by design based silymarin nanoemulsion for enhancement of oral bioavailability. J. Drug Deliv. Sci. Technol., 2017, 40, 35-44.
[http://dx.doi.org/10.1016/j.jddst.2017.05.019]
[201]
Piazzini, V.; Rosseti, C.; Bigagli, E.; Luceri, C.; Bilia, A.; Bergonzi, M. Prediction of permeation and cellular transport of Silybum marianum extract formulated in a nanoemulsion by using PAMPA and Caco-2 cell models. Planta Med., 2017, 83(14/15), 1184-1193.
[http://dx.doi.org/10.1055/s-0043-110052] [PMID: 28472840]
[202]
Woo, J.S.; Kim, T.S.; Park, J.H.; Chi, S.C. Formulation and biopharmaceutical evaluation of silymarin using SMEDDS. Arch. Pharm. Res., 2007, 30(1), 82-89.
[http://dx.doi.org/10.1007/BF02977782] [PMID: 17328246]
[203]
El-Far, M.; Salah, N.; Essam, A.; Abd El-Azim, A.O.; El-Sherbiny, I.M. Silymarin nanoformulation as potential anticancer agent in experimental Ehrlich ascites carcinoma-bearing animals. Nanomedicine, 2018, 13(15), 1865-1858.
[http://dx.doi.org/10.2217/nnm-2017-0394] [PMID: 30136915]
[204]
Nguyen, M.H.; Yu, H.; Dong, B.; Hadinoto, K. A supersaturating delivery system of silibinin exhibiting high payload achieved by amorphous nano-complexation with chitosan. Eur. J. Pharm. Sci., 2016, 89, 163-171.
[http://dx.doi.org/10.1016/j.ejps.2016.04.036] [PMID: 27140843]
[205]
Takke, A.; Shende, P. Nanotherapeutic silibinin: An insight of phytomedicine in healthcare reformation. Nanomedicine, 2019, 21, 102057.
[http://dx.doi.org/10.1016/j.nano.2019.102057] [PMID: 31340181]
[206]
Tan, J.M.; Karthivashan, G.; Arulselvan, P.; Fakurazi, S.; Hussein, M.Z. Characterization and in vitro sustained release of silibinin from pH responsive carbon nanotube-based drug delivery system. J. Nanomater., 2014, 2014, 1.
[207]
Adhikari, M.; Arora, R. Nano-silymarin provides protection against γ-radiation-induced oxidative stress in cultured human embryonic kidney cells. Mutat. Res. Genet. Toxicol. Environ. Mutagen., 2015, 792, 1-11.
[http://dx.doi.org/10.1016/j.mrgentox.2015.08.006] [PMID: 26433256]
[208]
Azadpour, M.; Farajollahi, M.M.; Dariushnejad, H.; Varzi, A.M.; Varezardi, A.; Barati, M. Effects of synthetic silymarin-PLGA nanoparticles on M2 polarization and inflammatory cytokines in LPS-treated murine peritoneal macrophages. Iran. J. Basic Med. Sci., 2021, 24(10), 1446-1454.
[PMID: 35096304]
[209]
Mombeini, M.; Saki, G.; Khorsandi, L.; Bavarsad, N. Effects of silymarin-loaded nanoparticles on HT-29 human colon cancer cells. Medicina., 2018, 54(1), 1.
[http://dx.doi.org/10.3390/medicina54010001] [PMID: 30344232]
[210]
Hosseini, S.; Rezaei, S.; Moghaddam, M.R.N.; Elyasi, S.; Karimi, G. Evaluation of oral nano-silymarin formulation efficacy on prevention of radiotherapy induced mucositis: A randomized, double-blinded, placebo-controlled clinical trial. PharmaNutrition, 2021, 15, 100253.
[http://dx.doi.org/10.1016/j.phanu.2021.100253]
[211]
Ghalehkhondabi, V.; Soleymani, M.; Fazlali, A. Folate-targeted nanomicelles containing silibinin as an active drug delivery system for liver cancer therapy. J. Drug Deliv. Sci. Technol., 2021, 61, 102157.
[http://dx.doi.org/10.1016/j.jddst.2020.102157]
[212]
Ripoli, M.; Angelico, R.; Sacco, P.; Ceglie, A.; Mangia, A. Phytoliposome-based silibinin delivery system as a promising strategy to prevent hepatitis c virus infection. J. Biomed. Nanotechnol., 2016, 12(4), 770-780.
[http://dx.doi.org/10.1166/jbn.2016.2161] [PMID: 27301203]

Rights & Permissions Print Cite
Article Metrics
23
1
Wayfinder Image
Open Access Journals Promotions
World Antimicrobial Awareness Week
© 2024 Bentham Science Publishers | Privacy Policy