Login Register Cart 0
Generic placeholder image

Current Vascular Pharmacology

Editor-in-Chief

ISSN (Print): 1570-1611
ISSN (Online): 1875-6212

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
General Review Article

Anti-Angiogenic Activity of Curcumin in Cancer Therapy: A Narrative Review

Author(s): Abolfazl Shakeri, Natalie Ward, Yunes Panahi and Amirhossein Sahebkar *

Volume 17, Issue 3, 2019

Page: [262 - 269] Pages: 8

DOI: 10.2174/1570161116666180209113014

Price: $65

Open Access Journals Promotions 2
conference banner
Abstract

Curcumin is a naturally occurring polyphenol isolated from Curcuma longa that has various pharmacological activities, including, anti-inflammatory, anti-oxidant and anti-cancer properties. The anticancer effect of curcumin is attributed to activation of apoptotic pathways in cancer cells, as well as inhibition of inflammation and angiogenesis in the tumour microenvironment and suppression of tumour metastasis. Angiogenesis, which is the formation of new blood vessels from pre-existing ones, is a fundamental step in tumour growth and expansion. Several reports have demonstrated that curcumin inhibits angiogenesis in a wide variety of tumour cells through the modulation of various cell signaling pathways which involve transcription factors, protein kinases, growth factors and enzymes. This review provides an updated summary of the various pathways and molecular targets that are regulated by curcumin to elicit its anti-angiogenic activity.

Keywords: Curcuminoids, neovascularization, cancer, vascular endothelial growth factor, angiogenesis, obesity.

« Previous Next »
Graphical Abstract

[1]
Zhang L, Shan Y, Li C, et al. Discovery of novel anti-angiogenesis agents. Part 6: Multi-targeted RTK inhibitors. Eur J Med Chem 2017; 127: 275-85.
[2]
Wu L, Chen L, Li L. Apelin/APJ system: A novel promising therapy target for pathological angiogenesis. Clin Chim Acta 2016; 466: 78-84.
[3]
Prauchner CA. Angiogenesis inhibition by antioxidants. IJBSE 2014; 2: 7-19.
[4]
Lin Z, Zhang Q, Luo W. Angiogenesis inhibitors as therapeutic agents in cancer: challenges and future directions. Eur J Pharmacol 2016; 793: 76-81.
[5]
Norooznezhad AH, Norooznezhad F. Cannabinoids: possible agents for treatment of psoriasis via suppression of angiogenesis and inflammation. Med Hypotheses 2016; 99: 15-8.
[6]
Elice F, Rodeghiero F. Side effects of anti-angiogenic drugs. Thromb Res 2012; 129: 50-3.
[7]
Morbidelli L. Polyphenol-based nutraceuticals for the control of angiogenesis: Analysis of the critical issues for human use. Pharmacol Res 2016; 111: 384-93.
[8]
Abdel-Qadir H, Ethier J-L, Lee DS, et al. Cardiovascular toxicity of angiogenesis inhibitors in treatment of malignancy: a systematic review and meta-analysis. Cancer Treat Rev 2016; 53: 120-7.
[9]
Ghatalia P, Je Y, Kaymakcalan MD, et al. QTc interval prolongation with vascular endothelial growth factor receptor tyrosine kinase inhibitors. Br J Cancer 2015; 112: 296-305.
[10]
Jiang C, Agarwal R, Lü J. Anti-angiogenic potential of a cancer chemopreventive flavonoid antioxidant, silymarin: inhibition of key attributes of vascular endothelial cells and angiogenic cytokine secretion by cancer epithelial cells. Biochem Biophys Res Commun 2000; 276: 371-8.
[11]
Sahebkar A. Curcuminoids for the management of hypertriglyceridaemia. Nat Rev Cardiol 2014; 11: 123.
[12]
Abdollahi E, Momtazi AA, Johnston TP, et al. Therapeutic effects of curcumin in inflammatory and immune-mediated diseases: a nature-made jack-of-all-trades? J Cell Physiol 2018; 233(2): 830-48.
[13]
Panahi YRA, Sharafi M, Alishiri G, Saburi A, Sahebkar A. Curcuminoid treatment for knee osteoarthritis: a randomized double-blind placebo-controlled trial. Phytother Res 2014; 28: 1625-31.
[14]
Sahebkar A, Henrotin Y. Analgesic efficacy and safety of curcuminoids in clinical practice: a systematic review and meta-analysis of randomized controlled trials. Pain Med 2016; 17: 1192-202.
[15]
Ganjali S, Blesso CN, Banach M, et al. Effects of curcumin on HDL functionality. Pharmacol Res 2017; 119: 208-18.
[16]
Lelli D, Sahebkar A, Johnston TP, et al. Curcumin use in pulmonary diseases: State of the art and future perspectives. Pharmacol Res 2017; 115: 133-48.
[17]
Rahmani S, Asgary S, Askari G, et al. Treatment of non-alcoholic fatty liver disease with curcumin: a randomized placebo-controlled trial. Phytother Res 2016; 30: 1540-8.
[18]
Iranshahi M, Sahebkar A, Hosseini ST, et al. Cancer chemopreventive activity of diversin from Ferula diversivittata in vitro and in vivo. Phytomedicine 2010; 17: 269-73.
[19]
Sahebkar A, Cicero AFG, Simental-Mendía LE, et al. Curcumin downregulates human tumor necrosis factor-α levels: A systematic review and meta-analysis of randomized controlled trials. Pharmacol Res 2016; 107: 234-42.
[20]
Panahi Y, Ghanei M, Bashiri S, et al. Short-term curcuminoid supplementation for chronic pulmonary complications due to sulfur mustard intoxication: positive results of a randomized double-blind placebo-controlled trial. Drug Res 2014; 65: 567-73.
[21]
Ganjali S, Sahebkar A, Mahdipour E, et al. Investigation of the effects of curcumin on serum cytokines in obese individuals: A randomized controlled trial. Scientific World J 2014; 898361.
[22]
Panahi Y, Alishiri GH, Parvin S, et al. Mitigation of systemic oxidative stress by curcuminoids in osteoarthritis: results of a randomized controlled trial. J Diet Suppl 2016; 13: 209-20.
[23]
Rezaee R, Momtazi AA, Monemi A, et al. Curcumin: a potentially powerful tool to reverse cisplatin-induced toxicity. Pharmacol Res 2016; 117: 218-27.
[24]
Teymouri M, Pirro M, Johnston TP, et al. Curcumin as a multifaceted compound against human papilloma virus infection and cervical cancers: A review of chemistry, cellular, molecular, and preclinical features. Biofactors 2016; 43: 331-46.
[25]
Mirzaei H, Naseri G, Rezaee R, et al. Curcumin: A new candidate for melanoma therapy? Int J Cancer 2016; 139: 1683-95.
[26]
Ramezani M, Hatamipour M, Sahebkar A. Promising Anti-tumor properties of bisdemethoxycurcumin: a naturally occurring curcumin analogue. J Cell Physiol 2018; 233: 880-7.
[27]
Momtazi AA, Shahabipour F, Khatibi S, et al. Curcumin as a microrna regulator in cancer: a review. Rev Physiol Biochem Pharmacol 2016; 171: 1-38.
[28]
Wang Z, Dabrosin C, Yin X, et al. Broad targeting of angiogenesis for cancer prevention and therapy. Semin Cancer Biol 2015; 35: 224-43.
[29]
Kunnumakkara AB, Anand P, Aggarwal BB. Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer Lett 2008; 269: 199-225.
[30]
Perry MC, Demeule M, Regina A, et al. Curcumin inhibits tumor growth and angiogenesis in glioblastoma xenografts. Mol Nutr Food Res 2010; 54: 1192-201.
[31]
Woo MS, Jung SH, Kim SY, et al. Curcumin suppresses phorbol ester-induced matrix metalloproteinase-9 expression by inhibiting the PKC to MAPK signaling pathways in human astroglioma cells. Biochem Biophys Res Commun 2005; 335: 1017-25.
[32]
Bimonte S, Barbieri A, Palma G, et al. Dissecting the role of curcumin in tumour growth and angiogenesis in mouse model of human breast cancer. BioMed Res Int 2015; 2015: 1-7.
[33]
Bimonte S, Barbieri A, Palma G, et al. Curcumin inhibits tumor growth and angiogenesis in an orthotopic mouse model of human pancreatic cancer. BioMed Res Int 2013; 2013: 1-8.
[34]
Vyas D, Gupt S, Dixit V, et al. To study the effect of curcumin on the growth properties of circulating endothelial progenitor cells. In Vitro Cell Dev Biol Anim 2015; 51: 488-94.
[35]
Zhang Y, Cao H, Hu YY, et al. Inhibitory effect of curcumin on angiogenesis in ectopic endometrium of rats with experimental endometriosis. Int J Mol Med 2011; 27: 87.
[36]
Zhang F, Zhang Z, Chen L, et al. Curcumin attenuates angiogenesis in liver fibrosis and inhibits angiogenic properties of hepatic stellate cells. J Cell Mol Med 2014; 18: 1392-406.
[37]
Yao Q, Lin Y, Li X, et al. Curcumin ameliorates intrahepatic angiogenesis and capillarization of the sinusoids in carbon tetrachloride-induced rat liver fibrosis. Toxicol Lett 2013; 222: 72-82.
[38]
Ejaz A, Wu D, Kwan P, et al. Curcumin inhibits adipogenesis in 3T3-L1 adipocytes and angiogenesis and obesity in C57/BL mice. J Nutr 2009; 139: 919-25.
[39]
Sharma AV, Ganguly K, Paul S, et al. Curcumin heals indomethacin-induced gastric ulceration by stimulation of angiogenesis and restitution of collagen fibers via VEGF and MMP-2 mediated signaling. Antioxid Redox Signal 2012; 16: 351-62.
[40]
Kant V, Gopal A, Kumar D, et al. Curcumin-induced angiogenesis hastens wound healing in diabetic rats. J Surg Res 2015; 193: 978-88.
[41]
Yodkeeree S, Chaiwangyen W, Garbisa S, et al. Curcumin, demethoxycurcumin and bisdemethoxycurcumin differentially inhibit cancer cell invasion through the down-regulation of MMPs and uPA. J Nutr Biochem 2009; 20: 87-95.
[42]
Kim J-M, Noh E-M, Kwon K-B, et al. Curcumin suppresses the TPA-induced invasion through inhibition of PKCα-dependent MMP-expression in MCF-7 human breast cancer cells. Phytomedicine 2012; 19: 1085-92.
[43]
Bandyopadhyay D. Farmer to pharmacist: curcumin as an anti-invasive and antimetastatic agent for the treatment of cancer. Front Chem 2014; 2: 113.
[44]
Xu X, Qin J, Liu W. Curcumin inhibits the invasion of thyroid cancer cells via down-regulation of PI3K/Akt signaling pathway. Gene 2014; 546: 226-32.
[45]
Zhang L, Cheng X, Gao Y, et al. Curcumin inhibits metastasis in human papillary thyroid carcinoma BCPAP cells via down-regulation of the TGF-β/Smad2/3 signaling pathway. Exp Cell Res 2016; 341: 157-65.
[46]
Zhang C-Y, Zhang L, Yu H-X, et al. Curcumin inhibits invasion and metastasis in K1 papillary thyroid cancer cells. Food Chem 2013; 139: 1021-8.
[47]
Tsai C-F, Hsieh T-H, Lee J-N, et al. Curcumin suppresses phthalate-induced metastasis and the proportion of cancer stem cell (CSC)-like cells via the inhibition of AhR/ERK/SK1 signaling in hepatocellular carcinoma. J Agric Food Chem 2015; 63: 10388-98.
[48]
Killian PH, Kronski E, Michalik KM, et al. Curcumin inhibits prostate cancer metastasis in vivo by targeting the inflammatory cytokines CXCL1 and-2. Carcinogenesis 2012; 33: 2507-19.
[49]
Mudduluru G, George-William JN, Muppala S, et al. Curcumin regulates miR-21 expression and inhibits invasion and metastasis in colorectal cancer. Biosci Rep 2011; 31: 185-97.
[50]
Chen C-C, Sureshbabul M, Chen H-W, et al. Curcumin suppresses metastasis via Sp-1, FAK inhibition, and E-cadherin upregulation in colorectal cancer. Evid Based Complement Alternat Med 2013; 2013: 1-17.
[51]
Lin S-S, Lai K-C, Hsu S-C, et al. Curcumin inhibits the migration and invasion of human A549 lung cancer cells through the inhibition of matrix metalloproteinase-2 and-9 and vascular endothelial growth factor (VEGF). Cancer Lett 2009; 285: 127-33.
[52]
Mirzaei H, Shakeri A, Rashidi B, et al. Phytosomal curcumin: A review of pharmacokinetic, experimental and clinical studies. Biomed Pharmacother 2017; 85: 102-12.
[53]
Gong C, Deng S, Wu Q, et al. Improving antiangiogenesis and anti-tumor activity of curcumin by biodegradable polymeric micelles. Biomaterials 2013; 34: 1413-32.
[54]
Gao X, Zheng F, Guo G, et al. Improving the anti-colon cancer activity of curcumin with biodegradable nano-micelles. J Mater Chem B 2013; 1: 5778-90.
[55]
Ibrahim A, El-Meligy A, Fetaih H, et al. Effect of curcumin and Meriva on the lung metastasis of murine mammary gland adenocarcinoma. In Vivo 2010; 24: 401-8.
[56]
Rajagopalan R. BDMC-A, an analog of curcumin, inhibits markers of invasion, angiogenesis, and metastasis in breast cancer cells via NF-kB pathway-A comparative study with curcumin. Biomed Pharmacother 2015; 74: 178-86.
[57]
Li S, Jin L, Sen-Sen L, et al. Potent anti-angiogenicactivity of B19-a mono-carbonyl analogue of curcumin. Chin J Nat Med 2014; 12: 8-14.
[58]
Koo H-J, Shin S, Choi JY, et al. Introduction of methyl groups at C2 and C6 positions enhances the antiangiogenesis activity of curcumin. Sci Rep 2015; 5: 1-12.
[59]
Pei H, Yang Y, Cui L, et al. Bisdemethoxycurcumin inhibits ovarian cancer via reducing oxidative stress mediated MMPs expressions. Sci Rep 2016; 6: 1-8.
[60]
Xu J, Yang H, Zhou X, et al. Bisdemethoxycurcumin suppresses migration and invasion of highly metastatic 95D lung cancer cells by regulating E-cadherin and vimentin expression, and inducing autophagy. Mol Med Rep 2015; 12: 7603-8.
[61]
Kim JH, Shim JS, Lee SK, et al. Microarray-based analysis of anti-angiogenic activity of demethoxycurcumin on human umbilical vein endothelial cells: crucial involvement of the down-regulation of matrix metalloproteinase. Jpn J Cancer Res 2002; 93: 1378-85.
[62]
Huang Y, Zhu X, Ding Z, et al. Study on anti-angiogenesis effect of three curcumin pigments and expression of their relevant factors. Zhongguo Zhongyao Zazhi 2015; 40: 324-9.
[63]
Meng YC, Ding ZY, Wang HQ, et al. Effect of microRNA-155 on angiogenesis after cerebral infarction of rats through AT1R/VEGFR2 pathway. Asian Pac J Trop Med 2015; 8: 829-35.
[64]
Lellia D, Pedone C, Sahebkar A. Curcumin and treatment of melanoma: The potential role of microRNAs. Biomed Pharmacother 2017; 88: 832-4.
[65]
Zhou B, Ma R, Si W, et al. MicroRNA-503 targets FGF2 and VEGFA and inhibits tumor angiogenesis and growth. Cancer Lett 2013; 333: 159-69.
[66]
Paul J. Davis, Leinung M, Mousa SA. microRNAs and angiogenesis. In Anti-angiogenesis strategies in cancer therapies, 1st ed. Elsevier Science 2016; p. 69-84.
[67]
Wu F, Yang Z, Li G. Role of specific microRNAs for endothelial function and angiogenesis. Biochem Biophys Res Commun 2009; 386: 549-53.
[68]
Simental-Mendia LE, Sahebkar A. Modulation of microRNAs by curcumin in pancreatic cancer. Clin Nutr 2016; 35: 1585.
[69]
Zhou S, Zhang S, Shen H, et al. Curcumin inhibits cancer progression through regulating expression of microRNAs. Tumour Biol 2017; 39: 1-12.
[70]
Ranjan K, Sharma A, Surolia A, et al. Regulation of HA14‐1 mediated oxidative stress, toxic response, and autophagy by curcumin to enhance apoptotic activity in human embryonic kidney cells. Biofactors 2014; 40: 157-69.
[71]
Kronski E, Fiori ME, Barbieri O, et al. miR181b is induced by the chemopreventive polyphenol curcumin and inhibits breast cancer metastasis via down-regulation of the inflammatory cytokines CXCL1 and -2. Mol Oncol 2014; 8: 581-95.
[72]
Sreenivasan S, Thirumalai K, Danda R, et al. Effect of curcumin on miRNA expression in human Y79 retinoblastoma cells. Curr Eye Res 2012; 37: 421-8.
[73]
Saini S, Arora S, Majid S, et al. Curcumin modulates microRNA-203-mediated regulation of the Src-Akt axis in bladder cancer. Cancer Prev Res (Phila) 2011; 4: 1698-709.
[74]
Jiao DM, Yan L, Wang LS, et al. Exploration of inhibitory mechanisms of curcumin in lung cancer metastasis using a miRNA- transcription factor-target gene network. PLoS One 2017; 12: e0172470.
[75]
Sarkar S, Dubaybo H, Ali S, et al. Down-regulation of miR-221 inhibits proliferation of pancreatic cancer cells through up-regulation of PTEN, p27(kip1), p57(kip2), and PUMA. Am J Cancer Res 2013; 3: 465-77.
[76]
Soubani O, Ali AS, Logna F, et al. Re-expression of miR-200 by novel approaches regulates the expression of PTEN and MT1-MMP in pancreatic cancer. Carcinogenesis 2012; 33: 1563-71.
[77]
Korpal M, Kang Y. The emerging role of miR-200 family of microRNAs in epithelial-mesenchymal transition and cancer metastasis. RNA Biol 2008; 5: 115-9.

Rights & Permissions Print Cite
Article Metrics
83
8
1
1
Wayfinder Image
Open Access Journals Promotions
World Prematurity Day
© 2024 Bentham Science Publishers | Privacy Policy