Phenazine-1-carboxylic acid-induced apoptosis in human prostate cancer cells is mediated by reactive oxygen species generation and mitochondrial-related apoptotic pathway

Publication date: Available online 23 January 2016 Source:Journal of Applied Biomedicine Author(s): Valliappan Karuppiah, Kumarappan Alagappan, Kannan Sivakumar, Lakshmanan Kannan Phenazine-1-carboxylic acid has extensive pharmacological activity, including antibiotic and immunomodulatory, but the anticancer activity remains unknown. Treatment of prostate cancer cell line (DU145) with phenazine-1-carboxylic acid stimulated inhibition of cell proliferation in concentration- and time-dependent manner. Dual staining confirmed phenazine-1-carboxylic acid stimulated prostate cancer cell apoptosis in time-dependent manner. To investigate the exact mechanism, phenazine-1-carboxylic acid-stimulated oxidative stress and mitochondrial-related apoptotic pathway in human prostate cancer cells were examined in this study. Phenazine-1-carboxylic acid increased the generation of reactive oxygen species (ROS) in prostate cancer cell lines, which triggered the pro-apoptotic JNK signaling. Phosphorylated JNK stimulated the depolarization of mitochondrial membrane potential (ΔΨm) and downregulation of anti-apoptotic protein Bcl-2 related with the upregulation of pro-apoptotic protein Bax. Downregulation of anti-apoptotic Bcl-2 family protein in corresponding with loss of ΔΨm, stimulate the increased production of cytochrome c and apoptosis-inducing factor (AIF) from mitochondria, and ultimately induced the caspase-dependent and caspase-independent apoptosis. Altogether, the pres...
Source: Journal of Applied Biomedicine - Category: Biotechnology Source Type: research