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Current Molecular Pharmacology

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ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

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Research Article

Restoration of Altered Oncogenic and Tumor Suppressor microRNA Expression in Breast Cancer and Colorectal Cancer Cell using Epicatechin

Author(s): Sheetal Kiran, Abhilipsa Patra, Poonam Verma, Suvendu Purkait, Gaurav Chhabra, Praveen Kumar Guttula and Amit Ghosh*

Volume 16, Issue 8, 2023

Published on: 29 March, 2023

Article ID: e100223213562 Pages: 12

DOI: 10.2174/1874467216666230210091839

Price: $65

Abstract

Background: MicroRNAs (miRNA) are small non-coding RNAs that regulate the function of mRNA post-transcriptionally in a tissue-specific manner. miRNA expressions are heavily dysregulated in human cancer cells through various mechanisms, including epigenetic changes, karyotype abnormalities, and miRNA biogenesis defects. miRNAs may act as either oncogenes or tumor suppressors under different conditions. Epicatechin is a natural compound found in green tea which possesses antioxidant and antitumor properties.

Objective: The objective of this study is to investigate the effect of epicatechin treatment on the expression level of several oncogenic and tumor suppressor miRNAs in breast and colorectal cancer cell lines (MCF7 and HT-29) and identify its mechanism of action.

Methods: The MCF-7 and HT29 cells were treated with epicatechin for 24 hours and untreated cells were considered control cultures. miRNA was isolated and qRT-PCR was used to measure the expression profile changes of different oncogenic and tumor suppressor miRNAs. Furthermore, the mRNA expression profile was also screened at different concentrations of epicatechin.

Results: Our results showed several-fold changes in miRNAs expression level, which is cell line specific. Also, epicatechin at different concentrations induces biphasic changes in mRNA expression levels in both cell lines.

Conclusion: Our findings first time demonstrated that epicatechin can reverse the expression of these miRNAs and may trigger the cytostatic effect at a lower concentration.

Keywords: Epicatechin, microRNA, apoptosis, MCF7, and HT29 cell line, cancer cells, tumor suppressor, ocogenic.

Graphical Abstract

[1]
Catalanotto, C.; Cogoni, C.; Zardo, G. MicroRNA in control of gene expression: an overview of nuclear functions. Int. J. Mol. Sci., 2016, 17(10), 1712.
[http://dx.doi.org/10.3390/ijms17101712] [PMID: 27754357]
[2]
Calin, G.A.; Sevignani, C.; Dumitru, C.D.; Hyslop, T.; Noch, E.; Yendamuri, S.; Shimizu, M.; Rattan, S.; Bullrich, F.; Negrini, M.; Croce, C.M. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc. Natl. Acad. Sci., 2004, 101(9), 2999-3004.
[http://dx.doi.org/10.1073/pnas.0307323101] [PMID: 14973191]
[3]
Pereyra-Vergara, F.; Olivares-Corichi, I.M.; Perez-Ruiz, A.G.; Luna-Arias, J.P.; García-Sánchez, J.R. Apoptosis induced by (−)-epicatechin in human breast cancer cells is mediated by reactive oxygen species. Molecules, 2020, 25(5), 1020.
[http://dx.doi.org/10.3390/molecules25051020] [PMID: 32106523]
[4]
Xu, X.L.; Chen, S.Z.; Chen, W.; Zheng, W.H.; Xia, X.H.; Yang, H.J.; Li, B.; Mao, W.M. The impact of cyclin D1 overexpression on the prognosis of ER-positive breast cancers: a meta-analysis. Breast Cancer Res. Treat., 2013, 139(2), 329-339.
[http://dx.doi.org/10.1007/s10549-013-2563-5] [PMID: 23670132]
[5]
Gryder, B.E.; Sodji, Q.H.; Oyelere, A.K. Targeted cancer therapy: giving histone deacetylase inhibitors all they need to succeed. Future Med. Chem., 2012, 4(4), 505-524.
[http://dx.doi.org/10.4155/fmc.12.3] [PMID: 22416777]
[6]
Ogino, S.; Lochhead, P.; Giovannucci, E.; Meyerhardt, J.A.; Fuchs, C.S.; Chan, A.T. Discovery of colorectal cancer PIK3CA mutation as potential predictive biomarker: power and promise of molecular pathological epidemiology. Oncogene, 2014, 33(23), 2949-2955.
[http://dx.doi.org/10.1038/onc.2013.244] [PMID: 23792451]
[7]
Jug, U.; Naumoska, K.; Vovk, I. (−)-Epicatechin—an important contributor to the antioxidant activity of Japanese knotweed rhizome bark extract as determined by antioxidant activity-guided fractionation. Antioxidants, 2021, 10(1), 133.
[http://dx.doi.org/10.3390/antiox10010133] [PMID: 33477734]
[8]
Grzesik, M.; Naparło, K.; Bartosz, G.; Sadowska-Bartosz, I. Antioxidant properties of catechins: Comparison with other antioxidants. Food Chem., 2018, 241, 480-492.
[http://dx.doi.org/10.1016/j.foodchem.2017.08.117] [PMID: 28958556]
[9]
Wang, H.; Cao, Z. Anti-inflammatory effects of (-)-epicatechin in lipopolysaccharide-stimulated raw 264.7 macrophages. Trop. J. Pharm. Res., 2014, 13(9), 1415.
[http://dx.doi.org/10.4314/tjpr.v13i9.6]
[10]
Vasconcelos, P.C.P.; Seito, L.N.; Di Stasi, L.C.; Akiko Hiruma-Lima, C.; Pellizzon, C.H. Epicatechin used in the treatment of intestinal inflammatory disease: an analysis by experimental models. Evid. Based Complement. Alternat. Med., 2012, 2012, 1-12.
[http://dx.doi.org/10.1155/2012/508902] [PMID: 23346204]
[11]
Yamazaki, K.G.; Taub, P.R.; Barraza-Hidalgo, M.; Rivas, M.M.; Zambon, A.C.; Ceballos, G.; Villarreal, F.J. Effects of (-)-epicatechin on myocardial infarct size and left ventricular remodeling after permanent coronary occlusion. J. Am. Coll. Cardiol., 2010, 55(25), 2869-2876.
[http://dx.doi.org/10.1016/j.jacc.2010.01.055] [PMID: 20579545]
[12]
Mangels, D.R.; Mohler, E.R., III Catechins as potential mediators of cardiovascular health. Arterioscler. Thromb. Vasc. Biol., 2017, 37(5), 757-763.
[http://dx.doi.org/10.1161/ATVBAHA.117.309048] [PMID: 28336557]
[13]
Kim, D.; Mollah, M.L.; Kim, K. Induction of apoptosis of SW480 human colon cancer cells by (-)-epicatechin isolated from Bulnesia sarmienti. Anticancer Res., 2012, 32(12), 5353-5361.
[PMID: 23225437]
[14]
Papież, M.A.; Baran, J.; Bukowska-Straková, K.; Wiczkowski, W. Antileukemic action of (−)-epicatechin in the spleen of rats with acute myeloid leukemia. Food Chem. Toxicol., 2010, 48(12), 3391-3397.
[http://dx.doi.org/10.1016/j.fct.2010.09.010] [PMID: 20837083]
[15]
Shay, J.; Elbaz, H.A.; Lee, I.; Zielske, S.P.; Malek, M.H.; Hüttemann, M. Molecular mechanisms and therapeutic effects of (−)-epicatechin and other polyphenols in cancer, inflammation, diabetes, and neurodegeneration. Oxid. Med. Cell. Longev., 2015, 2015, 1-13.
[http://dx.doi.org/10.1155/2015/181260] [PMID: 26180580]
[16]
Governa, P.; Manetti, F.; Miraldi, E.; Biagi, M. Effects of in vitro simulated digestion on the antioxidant activity of different Camellia sinen-sis (L.) Kuntze leaves extracts. Eur. Food Res. Technol., 2022, 248(1), 119-128.
[http://dx.doi.org/10.1007/s00217-021-03864-1]
[17]
Almaguer, G.; Ortiz-Vilchis, P.; Cordero, P.; Martinez-Vega, R.; Perez-Durán, J.; Meaney, E.; Villarreal, F.; Ceballos, G.; Nájera, N. Anti-cancer potential of (−)-epicatechin in a triple-negative mammary gland model. J. Pharm. Pharmacol., 2021, 73(12), 1675-1682.
[http://dx.doi.org/10.1093/jpp/rgab133] [PMID: 34473289]
[18]
Siddique, H.R.; Liao, D.J.; Mishra, S.K.; Schuster, T.; Wang, L.; Matter, B.; Campbell, P.M.; Villalta, P.; Nanda, S.; Deng, Y.; Saleem, M. Epicatechin-rich cocoa polyphenol inhibits Kras-activated pancreatic ductal carcinoma cell growth in vitro and in a mouse model. Int. J. Cancer, 2012, 131(7), 1720-1731.
[http://dx.doi.org/10.1002/ijc.27409] [PMID: 22190076]
[19]
Lee, Y-H.; Kwak, J.; Choi, H-K.; Choi, K.C.; Kim, S.; Lee, J.; Jun, W.; Park, H.J.; Yoon, H.G. EGCG suppresses prostate cancer cell growth modulating acetylation of androgen receptor by anti-histone acetyltransferase activity. Int. J. Mol. Med., 2012, 30(1), 69-74.
[PMID: 22505206]
[20]
Matteucci, E.; Rizvi, S.I.; Giampietro, O. Erythrocyte sodium/hydrogen exchange inhibition by (-) epicatechin. Cell Biol. Int., 2001, 25(8), 771-776.
[http://dx.doi.org/10.1006/cbir.2000.0719] [PMID: 11482900]
[21]
Rizvi, S.I.; Zaid, M.A. Impairment of sodium pump and Na/H exchanger in erythrocytes from non-insulin dependent diabetes mellitus patients: effect of tea catechins. Clin. Chim. Acta, 2005, 354(1-2), 59-67.
[http://dx.doi.org/10.1016/j.cccn.2004.11.008] [PMID: 15748600]
[22]
Marchbank, T.; Mahmood, A.; Playford, R.J. Pancreatic secretory trypsin inhibitor causes autocrine-mediated migration and invasion in bladder cancer and phosphorylates the EGF receptor, Akt2 and Akt3, and ERK1 and ERK2. Am. J. Physiol. Renal Physiol., 2013, 305(3), F382-F389.
[http://dx.doi.org/10.1152/ajprenal.00357.2012] [PMID: 23698120]
[23]
Ravindranath, M.H.; Saravanan, T.S.; Monteclaro, C.C.; Presser, N.; Ye, X.; Selvan, S.R.; Brosman, S. Epicatechins purified from green tea (Camellia sinensis) differentially suppress growth of gender-dependent human cancer cell lines. Evid. Based Complement. Alternat. Med., 2006, 3(2), 237-247.
[http://dx.doi.org/10.1093/ecam/nel003] [PMID: 16786054]
[24]
Tristán-Ramos, P.; Rubio-Roldan, A.; Peris, G.; Sánchez, L.; Amador-Cubero, S.; Viollet, S.; Cristofari, G.; Heras, S.R. The tumor sup-pressor microRNA let-7 inhibits human LINE-1 retrotransposition. Nat. Commun., 2020, 11(1), 5712.
[http://dx.doi.org/10.1038/s41467-020-19430-4] [PMID: 33177501]
[25]
Boyerinas, B.; Park, S.M.; Hau, A.; Murmann, A.E.; Peter, M.E. The role of let-7 in cell differentiation and cancer. Endocr. Relat. Cancer, 2010, 17(1), F19-F36.
[http://dx.doi.org/10.1677/ERC-09-0184] [PMID: 19779035]
[26]
Cimmino, A.; Calin, G.A.; Fabbri, M.; Iorio, M.V.; Ferracin, M.; Shimizu, M.; Wojcik, S.E.; Aqeilan, R.I.; Zupo, S.; Dono, M.; Rassenti, L.; Alder, H.; Volinia, S.; Liu, C.; Kipps, T.J.; Negrini, M.; Croce, C.M. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc. Natl. Acad. Sci., 2005, 102(39), 13944-13949.
[http://dx.doi.org/10.1073/pnas.0506654102] [PMID: 16166262]
[27]
Aqeilan, R.I.; Calin, G.A.; Croce, C.M. miR-15a and miR-16-1 in cancer: discovery, function and future perspectives. Cell Death Differ., 2010, 17(2), 215-220.
[http://dx.doi.org/10.1038/cdd.2009.69] [PMID: 19498445]
[28]
Peng, Y.; Croce, C.M. The role of MicroRNAs in human cancer. Signal Transduct. Target. Ther., 2016, 1(1), 15004.
[http://dx.doi.org/10.1038/sigtrans.2015.4] [PMID: 29263891]
[29]
Loh, H.Y.; Norman, B.P.; Lai, K.S.; Rahman, N.M.A.N.A.; Alitheen, N.B.M.; Osman, M.A. The regulatory role of micrornas in breast cancer. Int. J. Mol. Sci., 2019, 20(19), 4940.
[http://dx.doi.org/10.3390/ijms20194940] [PMID: 31590453]
[30]
Jiang, H.; Zhang, G.; Wu, J.H.; Jiang, C.P. Diverse roles of miR-29 in cancer. Oncol. Rep., 2014, 31(4), 1509-1516.
[http://dx.doi.org/10.3892/or.2014.3036] [PMID: 24573597]
[31]
Shi, X-Y.; Wang, H.; Wang, W.; Gu, Y-H. MiR-98-5p regulates proliferation and metastasis of MCF-7 breast cancer cells by targeting Gab2. Eur. Rev. Med. Pharmacol. Sci., 2020, 24(21), 10914.
[PMID: 33215398]
[32]
Fu, Y.; Liu, X.; Chen, Q.; Liu, T.; Lu, C.; Yu, J.; Miao, Y.; Wei, J. Downregulated miR-98-5p promotes PDAC proliferation and metastasis by reversely regulating MAP4K4. J. Exp. Clin. Cancer Res., 2018, 37(1), 130.
[http://dx.doi.org/10.1186/s13046-018-0807-2] [PMID: 29970191]
[33]
Zhang, N.; Hu, X.; Du, Y.; Du, J. The role of miRNAs in colorectal cancer progression and chemoradiotherapy. Biomed. Pharmacother., 2021, 134, 111099.
[http://dx.doi.org/10.1016/j.biopha.2020.111099] [PMID: 33338745]
[34]
Garrido-Cano, I.; Pattanayak, B.; Adam-Artigues, A.; Lameirinhas, A.; Torres-Ruiz, S.; Tormo, E.; Cervera, R.; Eroles, P. MicroRNAs as a clue to overcome breast cancer treatment resistance. Cancer Metastasis Rev., 2022, 41(1), 77-105.
[http://dx.doi.org/10.1007/s10555-021-09992-0] [PMID: 34524579]
[35]
Shahriar, A.; Ghaleh-Aziz, S.G.; Ghader, B.; Farhad, J.; Hosein, A.; Parsa, H. The dual role of mir-146a in metastasis and disease progres-sion. Biomed. Pharmacother., 2020, 126, 110099.
[36]
Abak, A.; Amini, S.; Sakhinia, E.; Abhari, A. MicroRNA-221: biogenesis, function and signatures in human cancers. Eur. Rev. Med. Pharmacol. Sci., 2018, 22(10), 3094-3117.
[PMID: 29863255]
[37]
Li, N.; Miao, Y.; Shan, Y.; Liu, B.; Li, Y.; Zhao, L.; Jia, L. MiR-106b and miR-93 regulate cell progression by suppression of PTEN via PI3K/Akt pathway in breast cancer. Cell Death Dis., 2017, 8(5), e2796.
[http://dx.doi.org/10.1038/cddis.2017.119] [PMID: 28518139]
[38]
Sagar, S.K. miR-106b as an emerging therapeutic target in cancer. Genes Dis., 2022, 9(4), 889-899.
[http://dx.doi.org/10.1016/j.gendis.2021.02.002] [PMID: 35685464]
[39]
Yin, W.; Chen, J.; Wang, G.; Zhang, D. MicroRNA-106b functions as an oncogene and regulates tumor viability and metastasis by targeting LARP4B in prostate cancer. Mol. Med. Rep., 2019, 20(2), 951-958.
[http://dx.doi.org/10.3892/mmr.2019.10343] [PMID: 31173237]
[40]
Stahlhut, E. C.E.; Slack, F.J. The role of microRNAs in cancer. Yale J. Biol. Med., 2006, 79(3-4), 131-140.
[PMID: 17940623]
[41]
Xiao, Z.; Chen, S.; Feng, S.; Li, Y.; Zou, J.; Ling, H.; Zeng, Y.; Zeng, X. Function and mechanisms of microRNA 20a in colorectal cancer.(Review) Exp. Ther. Med., 2020, 19(3), 1605-1616.
[http://dx.doi.org/10.3892/etm.2020.8432] [PMID: 32104211]
[42]
Liu, D.T.; Yao, H.R.; Li, Y.Y.; Song, Y.Y.; Su, M.Y. MicroRNA 19b promotes the migration and invasion of ovarian cancer cells by inhib-iting the PTEN/AKT signaling pathway. Oncol. Lett., 2018, 16(1), 559-565.
[http://dx.doi.org/10.3892/ol.2018.8695] [PMID: 29963131]
[43]
Liao, G.; Xiong, H.; Tang, J.; Li, Y.; Liu, Y. MicroRNA-92a inhibits the cell viability and metastasis of prostate cancer by targeting SOX4. Technol. Cancer Res. Treat., 2020, 19, 1533033820959354.
[http://dx.doi.org/10.1177/1533033820959354] [PMID: 32930086]
[44]
Yang, W.; Dou, C.; Wang, Y.; Jia, Y.; Li, C.; Zheng, X.; Tu, K. MicroRNA-92a contributes to tumor growth of human hepatocellular carci-noma by targeting FBXW7. Oncol. Rep., 2015, 34(5), 2576-2584.
[http://dx.doi.org/10.3892/or.2015.4210] [PMID: 26323375]
[45]
Zhang, S.; Yu, J.; Sun, B.; Hou, G.; Yu, Z.J.; Luo, H. MicroRNA-92a targets SERTAD3 and regulates the growth, invasion, and migration of prostate cancer cells via the P53 pathway. OncoTargets Ther., 2020, 13, 5495-5514.
[http://dx.doi.org/10.2147/OTT.S249168] [PMID: 32606766]
[46]
Son, T.G.; Camandola, S.; Mattson, M.P. Hormetic dietary phytochemicals. Neuromol. Med., 2008, 10(4), 236-246.
[http://dx.doi.org/10.1007/s12017-008-8037-y] [PMID: 18543123]
[47]
Calabrese, E.J.; Mattson, M.P.; Calabrese, V. Resveratrol commonly displays hormesis: Occurrence and biomedical significance. Hum. Exp. Toxicol., 2010, 29(12), 980-1015.
[http://dx.doi.org/10.1177/0960327110383625] [PMID: 21115559]
[48]
Speciale, A.; Chirafisi, J.; Saija, A.; Cimino, F. Nutritional antioxidants and adaptive cell responses: an update. Curr. Mol. Med., 2011, 11(9), 770-789.
[http://dx.doi.org/10.2174/156652411798062395] [PMID: 21999148]
[49]
Pietsch, K.; Saul, N.; Chakrabarti, S.; Stürzenbaum, S.R.; Menzel, R.; Steinberg, C.E.W. Hormetins, antioxidants and prooxidants: defining quercetin-, caffeic acid- and rosmarinic acid-mediated life extension in C. elegans. Biogerontology, 2011, 12(4), 329-347.
[http://dx.doi.org/10.1007/s10522-011-9334-7] [PMID: 21503726]
[50]
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]

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