title: Modulation of Tamoxifen Cytotoxicity by Caffeic Acid Phenethyl Ester in MCF-7 Breast Cancer Cells.
abstract: Although Tamoxifen (TAM) is one of the most widely used drugs in managing breast cancer, many women still relapse after long-term therapy. Caffeic acid phenethyl ester (CAPE) is a polyphenolic compound present in many medicinal plants and in propolis. The present study examined the effect of CAPE on TAM cytotoxicity in MCF-7 cells. MCF-7 cells were treated with different concentrations of TAM and/or CAPE for 48 h. This novel combination exerted synergistic cytotoxic effects against MCF-7 cells via induction of apoptotic machinery with activation of caspases and DNA fragmentation, along with downregulation of Bcl-2 and Beclin 1 expression levels. However, the mammalian microtubule-associated protein light chain LC 3-II level was unchanged. Vascular endothelial growth factor level was also decreased, whereas levels of glutathione and nitric oxide were increased. In conclusion, CAPE augmented TAM cytotoxicity via multiple mechanisms, providing a novel therapeutic approach for breast cancer treatment that can overcome resistance and lower toxicity. This effect provides a rationale for further investigation of this combination.
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
authors.forename: Tarek K
authors.initials: TK
authors.lastname: Motawi
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
authors.forename: Samy A
authors.initials: SA
authors.lastname: Abdelazim
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
authors.forename: Hebatallah A
authors.initials: HA
authors.lastname: Darwish
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
authors.forename: Eman M
authors.initials: EM
authors.lastname: Elbaz
authors.affiliation: Department of Cancer Biology, National Cancer Institute, Cairo University, Cairo 11796, Egypt.
authors.forename: Samia A
authors.initials: SA
authors.lastname: Shouman
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D000071186:Beclin-1; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002109:Caffeic Acids / Q000494:pharmacology; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008565:Membrane Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D051017:Apoptosis Regulatory Proteins; C000595707:BCL2 protein, human; C491997:BECN1 protein, human; D000071186:Beclin-1; D002109:Caffeic Acids; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D013629:Tamoxifen; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol