title: 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.
abstract: Breast cancer (BC) patients use alternative and natural remedies more than patients with other malignancies. Specifically, 63-83% use at least one type of alternative medicine and 25-63% use herbals and vitamins. Propolis is a naturopathic honeybee product, and CAPE (caffeic acid phenethyl ester), is a major medicinal component of propolis. CAPE, in a concentration dependent fashion, inhibits MCF-7 (hormone receptor positive, HR+) and MDA-231 (a model of triple negative BC (TNBC) tumor growth, both in vitro and in vivo without much effect on normal mammary cells and strongly influences gene and protein expression. It induces cell cycle arrest, apoptosis and reduces expression of growth and transcription factors, including NF-κB. Notably, CAPE down-regulates mdr-1 gene, considered responsible for the resistance of cancer cells to chemotherapeutic agents. Further, CAPE dose-dependently suppresses VEGF formation by MDA-231 cells and formation of capillary-like tubes by endothelial cells, implicating inhibitory effects on angiogenesis. In conclusion, our results strongly suggest that CAPE inhibits MDA-231 and MCF-7 human breast cancer growth via its apoptotic effects, and modulation of NF-κB, the cell cycle, and angiogenesis.
authors.affiliation: Dept. of Environmental Medicine, NYU School of Medicine, New York, 10016, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Coral
authors.initials: C
authors.lastname: Omene
authors.forename: Jerzy
authors.initials: J
authors.lastname: Karkoszka
authors.forename: Maarten
authors.initials: M
authors.lastname: Bosland
authors.forename: Jonathan
authors.initials: J
authors.lastname: Eckard
authors.forename: Catherine B
authors.initials: CB
authors.lastname: Klein
authors.forename: Krystyna
authors.initials: K
authors.lastname: Frenkel
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001516:Bees; D001943:Breast Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D002109:Caffeic Acids / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D011429:Propolis / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D002109:Caffeic Acids; D016328:NF-kappa B; D011429:Propolis; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol