title: Equol induces apoptosis through cytochrome c-mediated caspases cascade in human breast cancer MDA-MB-453 cells.
abstract: This study investigated the role of the caspase activation cascade in extrinsic and intrinsic apoptosis induced by equol in human breast cancer MDA-MB cells. First, the antiproliferative effect of equol was determined in cells treated with 1-100 microM equol for 24, 48, and 72h. Equol significantly inhibited cell proliferation in a dose-dependent manner (p<0.05). Exposure to 50 or 100 microM equol for 72h strongly promoted apoptosis. Under the same conditions, remarkable cytochrome c release was observed. Subsequently, caspase-9, which acts in mitochondria-mediated apoptosis, was cleaved by equol at high concentrations, but caspase-8 activation of receptor-mediated apoptosis was not observed. At both equol concentrations, the caspase-8 and -9 activity assays showed similar patterns. In addition, equol treatment activated caspase-3, which is downstream from caspase-9, and this was accompanied by the cleavage of capase-6 and -7. Activation of these caspases leads to increased activation of PARP, lamin, and ICAD. This study suggests that equol induces the intrinsic pathway of apoptosis via caspase-9 and cytochrome c, independent of caspase-8, in human breast cancer MDA-MB-453 cells.
authors.affiliation: Cancer Research Institute, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-040, Republic of Korea.
authors.forename: Eun Jeong
authors.initials: EJ
authors.lastname: Choi
authors.forename: Woong Shick
authors.initials: WS
authors.lastname: Ahn
authors.forename: Su Mi
authors.initials: SM
authors.lastname: Bae
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D060754:Equol; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*
chemical_list: C007610:4',7-dihydroxy-3,4-dihydroisoflavone; D007529:Isoflavones; D060754:Equol; D045304:Cytochromes c; D020169:Caspases