title: Cytotoxicity and apoptosis induction in human breast adenocarcinoma MCF-7 cells by (+)-cyanidan-3-ol.
abstract: The objective of this study was to evaluate the cytotoxicity and possible signalling pathway implicated in (+)-cyanidan-3-ol (CD-3) induced apoptosis in the human breast adenocarcinoma cell line (MCF-7). The effects of CD-3 on cell proliferation of MCF-7 cells were evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT), sulforhodamine B (SRB) and lactate dehydrogenase (LDH) assays. Cell apoptosis was detected by Hoechst 33258 (HO) and acridine orange/ethylene dibromide (AO/EB) staining and DNA fragmentation analysis. The expressions of apoptosis-related genes were assessed by RT-PCR and ELISA. Our data revealed that CD-3 induced MCF-7 cell death in a dose-dependent manner. Marked changes in apoptotic morphology was clearly observed after CD-3 treatment. CD-3 induced cell death was considered to be apoptotic by observing the typical apoptotic morphological change under fluorescent microscopy and DNA fragmentation assays. The induction of apoptosis is correlated with the increased mRNA expressions of p53, Bax, and caspase-3, -7, -8 and -9 and decreased mRNA expressions of bcl-2. Subsequently, CD-3 decreased the mRNA expressions of mdm2, p65, c-jun, c-fos in MCF-7 cells. The protein levels of p53, Bax, and caspase-3 were increased, whereas, that of p65, c-jun and Bcl-2 were decreased in MCF-7 cells on CD-3 treatment. These results clearly demonstrated that CD-3 effectively induced growth inhibition and apoptosis in MCF-7 cells.
authors.affiliation: Department of Pharmacy, Jaypee University of Information Technology, Waknaghat, Himachal Pradesh, India.
authors.forename: Jitender
authors.initials: J
authors.lastname: Monga
authors.forename: Saurabh
authors.initials: S
authors.lastname: Pandit
authors.forename: Chetan Singh
authors.initials: CS
authors.lastname: Chauhan
authors.forename: Manu
authors.initials: M
authors.lastname: Sharma
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000378:metabolism*; D002392:Catechin / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D061986:MCF-7 Cells; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D002392:Catechin
keywords: (+)-Cyanidan-3-ol; Apoptosis; Breast cancer; Cytotoxicity