title: Bax translocation to mitochondria is an important event in inducing apoptotic cell death by indole-3-carbinol (I3C) treatment of breast cancer cells.
abstract: Indole-3-carbinol (I3C), a natural component of Brassica vegetables, has been found to be a promising cancer preventive agent. However, the precise molecular mechanism(s) by which I3C exerts its inhibitory effects on cancer cells has not been fully elucidated. We investigated the molecular mechanism of action of I3C during apoptotic processes in breast epithelial cells. Nontumorigenic and tumorigenic breast epithelial cells were exposed to I3C, and growth inhibition, apoptosis and expression of genes involved in apoptotic processes were measured. Translocation of Bax to the mitochondria was accessed by confocal imaging. Mitochondrial potential and cytochrome c release also were measured. We found that I3C inhibited the growth of breast cancer cells and induced apoptosis in these cells, concomitant with upregulation of Bax, and downregulation of Bcl-2. I3C induced translocation of Bax to the mitochondria in both tumorigenic and nontumorigenic cells, but concomitant loss of mitochondrial potential, release of cytochrome c and induction of apoptosis were observed only in cancer cells. In conclusion, I3C exerts its effects by regulating cell cycle and by altering the expression of genes involved in apoptotic pathway. The translocation of Bax to the mitochondria alone is not sufficient during I3C-induced apoptosis. Translocation of Bax followed by mitochondrial depolarization and cytochrome c release is necessary, which may be responsible for selective induction of apoptosis in cancer cells, supporting the potential preventive and/or therapeutic benefit of I3C against cancers.
authors.affiliation: Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA. fsarkar@med.wayne.edu
authors.forename: Fazlul H
authors.initials: FH
authors.lastname: Sarkar
authors.forename: K M Wahidur
authors.initials: KM
authors.lastname: Rahman
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Li
mesh_terms: D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D016588:Anticarcinogenic Agents; D003574:Cytochrome c Group; D007211:Indoles; C016517:indole-3-carbinol