Indole-3-carbinol (I3C) induces apoptosis in tumorigenic but not in nontumorigenic breast epithelial cells.
Recent results from epidemiology, in vitro cell culture and in vivo (animal and human) studies have suggested the benefits of indole-3-carbinol (I3C) for the prevention of many types of cancer, including breast cancer. However, there are no reports, to the best of our knowledge, on the effect of I3C on isogenic nontumorigenic and tumorigenic breast epithelial cells, and there is a significant void in our understanding of the molecular mechanism(s) by which I3C induces apoptotic cell death in breast cancer cells. To fill this gap in our understanding, we conducted experiments to investigate the effects of I3C on an isogenic nontumorigenic (MCF10A) and tumorigenic (MCF10CA1a [CA1a]) breast epithelial cells. Here we show that CA1a cells are more sensitive to low concentration of I3C in terms of cell growth inhibition compared to MCF10A cells. We further report that I3C upregulates Bax/Bcl-2 ratio and downregulates Bcl-xL expression in CA1a cells but not in MCF10A cells. We also report, for the first time, that I3C induces Bax translocation to the mitochondria, causing mitochondrial depolarization, resulting in the loss of mitochondrial potential leading to the release of cytochrome c and subsequent cell death in CA1a cells but not in MCF10A cells. From these results, we conclude that I3C selectively induces apoptosis in breast cancer cells, but not in nontumorigenic breast epithelial cells, suggesting the potential therapeutic benefit of I3C against breast cancer.
Rahman
K M Wahidur
KM
Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Aranha
Olivia
O
Sarkar
Fazlul H
FH
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001940:Breast / Q000166:cytology / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019254:Genes, bcl-2 / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D016588:Anticarcinogenic Agents; C494826:BAX protein, human; C494811:BCL2L1 protein, human; D007211:Indoles; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D045304:Cytochromes c; C016517:indole-3-carbinol