cytochrome-c-t and indole-3-carbinol

Cruciferous vegetables contain glucobrassicin which, during metabolism, yields indole-3-carbinol (I3C). The aim of this study was to find whether indole-3-carbinol caused apoptosis and its mechanism in Candida albicans. We found that treatment of Candida albicans with indole-3-carbinol significantly increased the reactive oxygen species and hydroxyl radical accumulation. The hydroxyl radical is one of the most active components of oxygen, and it is the end product of an oxidative damage cellular death pathway. We investigated the general phenotypes of apoptosis and then investigated whether there were other distinct markers of apoptosis. Furthermore, the effects of thiourea as a hydroxyl radical scavenger and protective effect of trehalose, which is the result of the fungal immune system, was also assured. This study indicates that indole-3-carbinol has apoptosis effects, including a production of hydroxyl radicals, cytochrome c release and activation of metacaspase. Both hydroxyl radicals and metacaspases triggered apoptosis in Candida albicans.

Topics: Annexin A5; Antifungal Agents; Apoptosis; Biomarkers; Candida albicans; Cytochromes c; Drug Evaluation, Preclinical; Free Radicals; Glucosinolates; In Situ Nick-End Labeling; Indoles; Membrane Potential, Mitochondrial; Microbial Sensitivity Tests; Molecular Targeted Therapy; Reactive Oxygen Species; Thiourea

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.

Topics: Animals; Anticarcinogenic Agents; Apoptosis; bcl-2-Associated X Protein; bcl-X Protein; Breast; Breast Neoplasms; Cell Division; Cell Line, Tumor; Cells, Cultured; Cytochromes c; Down-Regulation; Epithelial Cells; Female; Flow Cytometry; Gene Expression Regulation, Neoplastic; Genes, bcl-2; Humans; Indoles; Mitochondria; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2