The effect of caffeic acid phenethyl ester on cell cycle control gene expressions in breast cancer cells

Document Type : Short communication

Authors

1 Vocational School of Health Sciences, Near East University, Nicosia, TRNC, Cyprus

2 Faculty of Medicine, Department of Medical Biology, Ege University, Bornova, Izmir, Turkey

Abstract

We aimed to find the effect of caffeic acid phenethyl ester (CAPE) on the expression profiles of cell cycle control genes in breast cancer cell line (MCF-7). The cytotoxic effect of CAPE on MCF-7 cell line was found with an XTT analysis. Total RNA was isolated from the cells exposed to IC50 dose and untreated control cells. Expressions of genes related to cell cycle control (CCND2, RB1, ATM, CDC34, CDK5RAP1) were evaluated by qRT-PCR by the LightCycler 480 System (Roche). GAPDH and ACTB housekeeping genes were used for the normalization of gene expressions. IC50 value of CAPE in MCF-7 cells was calculated as 75µM. It was shown that IC50 dose of CAPE induced significant upregulation in expressions of cell cycle control genes, compared to control cells. CAPE increases the expression of genes that are important in cell cycle control, suggesting that this component can be used as an effective chemopreventive agent in breast cancer cells.

Keywords

References

1. Kabała-Dzik A, Rzepecka-Stojko A, Kubina R, Wojtyczka RD, Buszman Ewa, Stojko J.  Caffeic Acid Versus Caffeic Acid Phenethyl Ester in the Treatment of Breast Cancer MCF-7 Cells: Migration Rate Inhibition. Integr Cancer Ther 2018;4:1247-1259.
2. Karaboğa İ. Caffeic acid phenethyl ester ameliorates pulmonary inflammation and apoptosis reducing Nf-κβ activation in blunt pulmonary contusion model. Ulus Travma Acil Cerrahi Derg 2019;25:433-439.
3. Hsu TH, Chu CC, Hung MW, Lee HJ, Hsu HJ, Chang TC. Caffeic acid phenethyl ester induces E2F‐1‐mediated growth inhibition and cell‐cycle arrest in human cervical cancer cells. FEBS J 2013;280:2581-2593.
4. Motomura M, Kwon KM, Suh SJ, Lee YC, Kim YK, Lee IS, Kim MS, Kwon DY, Suzuki I, Kim CH. Propolis induces cell cycle arrest and apoptosis in human leukemic U937 cells through Bcl-2/Bax regulation. Environ Toxicol Pharmacol 2008; 26:61-67.
5. Torki S, Soltani A, Shirzad H, Esmaeil N, Ghatrehsamani M. Synergistic antitumor effect of NVP-BEZ235 and CAPE on MDA-MB-231 breast cancer cells. Biomed Pharmacother 2017;92:39-45.
6. Wang L, Cui Y, Zhang L, Sheng J, Yang Y, Kuang G, Fan Y, Zhang Q, Jin J. The silencing of CCND2 by promoter aberrant methylation in renal cell cancer and cnalysis of the correlat-ion between CCND2 methylation status and clinical features. PLoS One 2016;11:e0161859.
7. Dyson NJ. RB1:a prototype tumor suppressor and an enigma. Genes Dev 2016;30:1492-1502.
8. Hisanori F, Yasuyuki T, Kevin MP. Diversity of ATM gene variants: a population-based genome data analysis for precision medicine. Hum Genomic 2019;13:38. 
9. Omene C, Karkoszka J, Bosland M, Eckard J, Klein CB, Frenkel K. Caffeic acid phenethyl ester (CAPE), derived from a honeybee product propolis, exhibits a diversity of anti-tumor effects in pre-clinical models of human breast cancer. Cancer Lett 2011;308,43-53.
10. Sanderson JT, Clabault H, Patton C, Lassalle-Claux G, Jean-François J, Paré AF, Hébert MJ, Surette ME, Touaibia M. Antiproliferative, antiandrogenic and cytotoxic effects of novel caffeic acid derivatives in LNCaP human androgen-dependent prostate cancer cells. Bioorg Med Chem 2013;21,7182-7193.
11. Agata KD , Anna RS, Robert K, Zaneta JS, Rafał S, Robert DW, Jerzy S. Comparison of two components of propolis: caffeic acid (CA) and caffeic acid phenethyl ester (CAPE) induce apoptosis and cell cycle arrest of breast cancer cells MDA-MB-231. Molecules 2017;15;22:1554.
12. Hung CS, Wang SC, Yen YT, Lee TH, Wen Wc, Lin RK. Hypermethylation of CCND2 in lung and breast cancer is a potential biomarker and drug target.Int J Mol Sci  2018;19:3096.   
13. Ding Zy, Li R, Zhang QJ, Wang Y, Jiang Y, Meng QY, Xi QL, Wu GH. Prognostic role of cyclin D2/D3 in multiple human malignant neoplasms: A systematic review and meta‐ analysis. Cancer Med 2019;8:2717-2729.   
14. Taube JH, Herschkowitz JI, Komurov K, Zhou AY, Gupta S, Yang J, Hartwell K, Onder TT, Gupta PB, Evans KW, Hollier BG, Ram PT, Lander ES, Rosen JM, Weinberg RA, Mani SA. Core epithelial‐to‐mesenchymal transition interactome gene‐expression signature is associated with claudin‐low and metaplastic breast cancer subtypes. Proc Natl Acad Sci USA 2010;107;15449‐15454.
15. Xiao-ping Z, Anna K, Yi-hong L, Lu LH, Mei J, Wei W, Li SH, Guo RP. NCKAP1 improves patient outcome and inhibits cell growth by enhancing Rb1/p53 activation in hepatocellular carcinoma Cell Death Dis 2019;10:369. 
16. Ranuncolo SM, Wang L, Polo JM, Oso TD, Dierov J, Gaymes TJ, Rasool F, Carroll M, Melnick A. BCL6‐ mediated attenuation of DNA damage sensing triggers growth arrest and senescence through a p53‐ dependent pathway in a cell context‐dependent manner. J Biol Chem 2008;283:22565‐22572.
17. Zhao XC, Wang GZ, Zhou YC, Ma L, Liu J, Zhang C, Zhang DL, Gao SH, Qu LW, Zhang B, Wang CL, Hang YC, Chen L, Zhou GB. Genome-wide identification of CDC34 that stabilizes EGFR and promotes lung carcinogenesis. BioRxiv 2018
18. Zindy P, Andrieux L, Bonnier D, Musso O, Langouet S, Campion JP, Turlin B, Clement B, Theret N. Upregulation of DNA repair genes in active cirrhosis associated with hepatocellular carcinomaFEBS Lett 2005;579:95-99.
19. Wang H, Wei L, Li C, Zhou J, Li Z. CDK5RAP1 deficiency induces cell cycle arrest and apoptosis in human breast cancer cell line by the ROS/JNK signaling pathway. Oncol Rep 2015;33:1089-1096.
20. Bridges CN. Prelamin A, influences a program of gene expression in regulation of cell cycle control electronic. Theses and Dissertations 2012;P:1213. East Tennessee State University.
 

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