Methylglyoxal-induced apoptosis in human prostate carcinoma: Potential modality for prostate cancer treatment

Objective: To examine the cellular effects of methylglyoxal (MG), a toxic p hysiological metabolite, on human prostatic cancer PC-3 cells. Methods: The effects of MG on cell growth and viability were evaluated firs t, and then its effects on the cell cycle and the glycolytic process were a nalyzed by Western blots and specific assays. Possible MG-induced apoptosis was also,assessed by DNA analysis using agarose gel electrophoresis. Results: MG greater than or equal to 3 mM caused severe growth inhibition, resulting in nearly 100% cell death by 24 h. The time course study revealed that expression of cyclin D-1, cdk2, and cdk4 was significantly (>50%) dow nregulated in 3 h of MG (3 mM) exposure, followed by the dephosphorylation of retinoblastoma protein by 6 h. Both the glyceraldehyde 3phosphate dehydr ogenase activity and the cellular lactate level were also reduced by simila r to 50 and 80%, respectively, following 6-hour MG exposure. Induction of a poptosis by MG was indicated by partial degradation of poly(ADP-ribose) pol ymerase and further confirmed by discrete DNA fragmentation detected on an agarose gel. Conclusion: MG is capable of inducing apoptosis in prostatic cancer PC-3 ce lls, due primarily to a blocking of the cell cycle progression (G(1) arrest ) and glycolytic pathway. Therefore, MG could be a potent apoptosis inducer , which may have a potential for prostate cancer treatment. Copyright (C) 2 000 S. Karger AG, Basel.