title: Could Caffeic Acid Phenethyl Ester Expand the Antitumor Effect of Tamoxifen in Breast Carcinoma?
abstract: Despite tamoxifen (TAM) is beneficial in treating a significant proportion of patients with breast cancer, many women still relapse after long-term therapy. Caffeic acid phenethyl ester (CAPE) is a component of honeybee propolis, with a plethora of important biological actions including anticancer activity. This study aimed to explore the cytotoxicity, the type of drugs interaction as well as the apoptotic and autophagic pathways of the combined treatment of TAM and CAPE in MCF-7 cells. Their antitumor activity and effect on survival of mice bearing Ehrlich tumor were also analyzed. The results showed synergistic cytotoxic effects, manifested by significant activation of apoptotic machinery, along with downregulation of protein levels of Bcl-2 and beclin-1, upon using the combination regimen. However, the ratio between microtubule-associated protein light chain 3-II and -I was not altered. Moreover, a decrease in vascular endothelial growth factor level was detected. Similarly, TAM + CAPE increased the life span of tumor-bearing animals and caused a marked regression in their tumor size and weight compared with those treated with either TAM or CAPE alone. In conclusion, CAPE relatively improved the anticancer activity of TAM in both in vitro and in vivo models via its apoptotic and angiostatic potentials.
authors.affiliation: a Department of Biochemistry , Faculty of Pharmacy, Cairo University , Cairo , Egypt.
authors.forename: Tarek K
authors.initials: TK
authors.lastname: Motawi
authors.affiliation: a Department of Biochemistry , Faculty of Pharmacy, Cairo University , Cairo , Egypt.
authors.forename: Samy A
authors.initials: SA
authors.lastname: Abdelazim
authors.affiliation: a Department of Biochemistry , Faculty of Pharmacy, Cairo University , Cairo , Egypt.
authors.forename: Hebatallah A
authors.initials: HA
authors.lastname: Darwish
authors.affiliation: a Department of Biochemistry , Faculty of Pharmacy, Cairo University , Cairo , Egypt.
authors.forename: Eman M
authors.initials: EM
authors.lastname: Elbaz
authors.affiliation: b Department of Cancer Biology , National Cancer Institute, Cairo University , Cairo , Egypt.
authors.forename: Samia A
authors.initials: SA
authors.lastname: Shouman
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002109:Caffeic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D061986:MCF-7 Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010626:Phenylethyl Alcohol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D013629:Tamoxifen / Q000008:administration & dosage / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D002109:Caffeic Acids; D011506:Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D013629:Tamoxifen; D053148:Caspase 3; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol