Metformin Induced-Hydrogen Sulfide Modulates Prostate Cancer Redox Status Promoting Antiproliferative Effects

Nova Southeastern University, Davie, Florida, USA

Objective: To determine the role of metformin-induced hydrogen sulfide (H2S) in regulating prostate cancer redox status and apoptotic induction. Background: Prostate cancer is the second leading cause of cancer related death among men in the United States. Despite, current therapeutic approaches, the rate of new cases of prostate cancer continues to increase yearly. Over the last decade, several in vitro and clinical studies demonstrate evidence for the possible use of metformin in cancer therapy. Recently, these effects have extended to the potential role of metformin in stimulating hydrogen sulfide production. We hypothesized that metformin treated prostate cancer cells will promote hydrogen sulfide production which will further potentiate metformin apoptotic-related effects. We further hypothesized that metformin-induced H2S alters mitochondrial functions and modulate transsulfuration pathway in prostate cancer cells. Methods. Using an ion-selective electrode, hydrogen sulfide content of the LNCaP androgen sensitive prostate cancer cells was measured. Real Time- quantitative polymerase chain reaction, Liquid Chromatography/ Mass Spectrometry and Apoptosis Assay was used to assess the role of metformin-induced H2S on the redox status and prostate cancer survival. Results. Metformin significantly decrease metabolites associated with transsulfuration and glutathione pathway. These effects were concordant with an increase in gene expression of H2S-synthesizing enzymes. These effects potentiated the apoptotic effect of metformin by increasing the gene expression of apoptotic-related gene and induces cell death. Conclusion. Metformin-induced H2S regulates prostate cancer redox status inducing apoptosis.