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Current Pharmaceutical Design

Author(s): Xin Zhao, Panfeng Feng, Wenqian He, Xing Du, Chao Chen, Lianhuan Suo, Min Liang, Na Zhang, An Na and Yan Zhang*

DOI: 10.2174/1381612825666191212105145

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The Prevention and Inhibition Effect of Anthocyanins on Colorectal Cancer

Page: [4919 - 4927] Pages: 9

  • * (Excluding Mailing and Handling)

Abstract

Background: Anthocyanins are a type of flavonoids that are natural water soluble glycosidic pigments with efficacious anti-cancer effects, which have good biological activity against many cancers including colorectal cancer (CRC). However, the exact molecular mechanism used by anthocyanins against cancer is unclear; it is also unclear what a reasonable dosage might be for their use against colorectal cancer.

Methods: Western blotting, immunohistochemistry, MTT assay, xenograft model, and hematoxylin-eosin (HE) staining were used to perform the experiments.

Results: Compared with the control group, anthocyanins could significantly inhibit the cell viability and proliferation and promote the apoptosis of human colon cancer HT29 cells. Furthermore, anthocyanins reduced tumor weight and volume in a colon tumor mouse model and downregulated the expression of PI3K protein, inhibited AKT expression and phosphorylation, decreased the Bcl-2 and Bax ratio and reduced survivin protein expression in the tumor tissue.

Conclusion: Anthocyanins promoted apoptosis of CRC cells and inhibited colon cancer growth of xenografted tumors. Mechanistically, anthocyanins enhanced the Bcl-2/Bax and caspase-dependent apoptotic pathways through targeting the PI3K/AKT/survivin pathway, resulting in impairment of growth of CRC.

Keywords: Anthocyanins, Colorectal Cancer, P13K/AKT, Bax/Bcl-2, Survivin, Caspase-3.

[1]
Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut 2017; 66(4): 683-91.
[http://dx.doi.org/10.1136/gutjnl-2015-310912] [PMID: 26818619]
[2]
Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 2013; 49(6): 1374-403.
[http://dx.doi.org/10.1016/j.ejca.2012.12.027] [PMID: 23485231]
[3]
Belwal T, Nabavi SF, Nabavi SM, Habtemariam S. Dietary anthocyanins and insulin resistance: when food becomes a medicine. Nutrients 2017; 9(10): 1111.
[http://dx.doi.org/10.3390/nu9101111] [PMID: 29023424]
[4]
Lee YM, Yoon Y, Yoon H, Park HM, Song S, Yeum KJ. Dietary anthocyanins against obesity and inflammation. Nutrients 2017; 9(10): 1089.
[http://dx.doi.org/10.3390/nu9101089] [PMID: 28974032]
[5]
Chedea VS, Braicu C, Chirilă F, et al. Antioxidant/Prooxidant and antibacterial/probacterial effects of a grape seed extract in complex with lipoxygenase. BioMed Res Int 2014; 2014 313684
[http://dx.doi.org/10.1155/2014/313684] [PMID: 25313359]
[6]
Phan MAT, Bucknall M, Arcot J. Effect of different anthocyanidin glucosides on lutein uptake by Caco-2 cells, and their combined activities on anti-oxidation and anti-inflammation and ex vivo. Molecules 2018; 23(8): 2035.
[http://dx.doi.org/10.3390/molecules23082035] [PMID: 30110956]
[7]
Chen H, Yu W, Chen G, Meng S, Xiang Z, He N. Antinociceptive and antibacterial properties of anthocyanins and flavonols from fruits of black and non-black mulberries. Molecules 2017; 23(1): 4.
[http://dx.doi.org/10.3390/molecules23010004] [PMID: 29267231]
[8]
Peiffer DS, Wang LS, Zimmerman NP, et al. Dietary consumption of black raspberries or their anthocyanin constituents alters innate immune cell trafficking in esophageal cancer. Cancer Immunol Res 2016; 4(1): 72-82.
[http://dx.doi.org/10.1158/2326-6066.CIR-15-0091] [PMID: 26603620]
[9]
Gaiz AA, Mosawy S, Colson N, Singh I. Potential of anthocyanin to prevent cardiovascular disease in diabetes. Altern Ther Health Med 2018; 24(3): 40-7.
[PMID: 29477135]
[10]
Różańska D, Regulska-Ilow B. The significance of anthocyanins in the prevention and treatment of type 2 diabetes. Adv Clin Exp Med 2018; 27(1): 135-42.
[http://dx.doi.org/10.17219/acem/64983] [PMID: 29521054]
[11]
Min HK, Kim SM, Baek SY, et al. Anthocyanin extracted from black soybean seed coats prevents autoimmune arthritis by suppressing the development of Th17 cells and synthesis of proinflammatory cytokines by such cells, via inhibition of NF-κB. PLoS One 2015; 10(11)e0138201
[http://dx.doi.org/10.1371/journal.pone.0138201] [PMID: 26544846]
[12]
de Sousa Moraes LF, Sun X, Peluzio MDCG, Zhu MJ. Anthocyanins/anthocyanidins and colorectal cancer: what is behind the scenes? Crit Rev Food Sci Nutr 2019; 59(1): 59-71.
[http://dx.doi.org/10.1080/10408398.2017.1357533] [PMID: 28799785]
[13]
Zhang L, Zhou J, Luo J, Wang Q, Liu J, Zeng QQ. Study on mulberry anthocyanins induced autophagy and apoptosis of human gastric cancer sgc-7901 cell autophagy Zhong Yao Cai 2016; 39(5): 1134-8.
[PMID: 30133211]
[14]
Chen L, Jiang B, Zhong C, et al. Chemoprevention of colorectal cancer by black raspberry anthocyanins involved the modulation of gut microbiota and SFRP2 demethylation. Carcinogenesis 2018; 39(3): 471-81.
[http://dx.doi.org/10.1093/carcin/bgy009] [PMID: 29361151]
[15]
Ha US, Bae WJ, Kim SJ, et al. Anthocyanin induces apoptosis of DU-145 cells and inhibits xenograft growth of prostate cancer. Yonsei Med J 2015; 56(1): 16-23.
[http://dx.doi.org/10.3349/ymj.2015.56.1.16] [PMID: 25510742]
[16]
Giampieri F, Gasparrini M, Forbes-Hernandez TY, et al. Overexpression of the anthocyanidin synthase gene in strawberry enhances antioxidant capacity and cytotoxic effects on human hepatic cancer cells. J Agric Food Chem 2018; 66(3): 581-92.
[http://dx.doi.org/10.1021/acs.jafc.7b04177] [PMID: 29291263]
[17]
Mazewski C, Liang K, de Mejia EG. Inhibitory potential of anthocyanin-rich purple and red corn extracts on human colorectal cancer cell proliferation. J Funct Foods 2017; 34: 254-65.
[http://dx.doi.org/10.1016/j.jff.2017.04.038]
[18]
Yue E, Tuguzbaeva G, Chen X, et al. Anthocyanin is involved in the activation of pyroptosis in oral squamous cell carcinoma. Phytomedicine 2019; 56: 286-94.
[http://dx.doi.org/10.1016/j.phymed.2018.09.223] [PMID: 30668350]
[19]
Newman DJ, Cragg GM. Natural products as sources of new drugs from 1981 to 2014. J Nat Prod 2016; 79(3): 629-61.
[http://dx.doi.org/10.1021/acs.jnatprod.5b01055] [PMID: 26852623]
[20]
Lippert E, Ruemmele P, Obermeier F, et al. Anthocyanins prevent colorectal cancer development in a mouse model. Digestion 2017; 95(4): 275-80.
[http://dx.doi.org/10.1159/000475524] [PMID: 28494451]
[21]
Fernández J, García L, Monte J, Villar CJ, Lombó F. Functional anthocyanin-rich sausages diminish colorectal cancer in an animal model and reduce pro-inflammatory bacteria in the intestinal microbiota. Genes (Basel) 2018; 9(3): 133.
[http://dx.doi.org/10.3390/genes9030133] [PMID: 29494510]
[22]
Kang HM, Park BS, Kang HK, Park HR, Yu SB, Kim IR. Delphinidin induces apoptosis and inhibits epithelial-to-mesenchymal transition via the ERK/p38 MAPK-signaling pathway in human osteosarcoma cell lines. Environ Toxicol 2018; 33(6): 640-9.
[http://dx.doi.org/10.1002/tox.22548] [PMID: 29451351]
[23]
Long HL, Zhang FF, Wang HL, et al. Mulberry anthocyanins improves thyroid cancer progression mainly by inducing apoptosis and autophagy cell death. Kaohsiung J Med Sci 2018; 34(5): 255-62.
[http://dx.doi.org/10.1016/j.kjms.2017.11.004] [PMID: 29699632]
[24]
Kubow S, Iskandar MM, Melgar-Bermudez E, et al. Effects of simulated human gastrointestinal digestion of two purple-fleshed potato cultivars on anthocyanin composition and cytotoxicity in colonic cancer and non-tumorigenic Cells. Nutrients 2017; 9(9): 953.
[http://dx.doi.org/10.3390/nu9090953] [PMID: 28850070]
[25]
Venancio VP, Cipriano PA, Kim H, Antunes LM, Talcott ST, Mertens-Talcott SU. Cocoplum (Chrysobalanus icaco L.) anthocyanins exert anti-inflammatory activity in human colon cancer and non-malignant colon cells. Food Funct 2017; 8(1): 307-14.
[http://dx.doi.org/10.1039/C6FO01498D] [PMID: 28009871]
[26]
López de Las Hazas MC, Mosele JI, Macià A, Ludwig IA, Motilva MJ. Exploring the colonic metabolism of grape and strawberry anthocyanins and their apoptotic effects in HT-29 colon cancer cells. J Agric Food Chem 2017; 65(31): 6477-87.
[http://dx.doi.org/10.1021/acs.jafc.6b04096] [PMID: 27790915]
[27]
Franke TF. PI3K/Akt: getting it right matters. Oncogene 2008; 27(50): 6473-88.
[http://dx.doi.org/10.1038/onc.2008.313] [PMID: 18955974]
[28]
Carnero A, Blanco-Aparicio C, Renner O, Link W, Leal JF. The PTEN/PI3K/AKT signalling pathway in cancer, therapeutic implications. Curr Cancer Drug Targets 2008; 8(3): 187-98.
[http://dx.doi.org/10.2174/156800908784293659] [PMID: 18473732]