Methylglyoxal-induced apoptosis in human prostate carcinoma: potential modality for prostate cancer treatment.
OBJECTIVE
To examine the cellular effects of methylglyoxal (MG), a toxic physiological metabolite, on human prostatic cancer PC-3 cells.


METHODS
The effects of MG on cell growth and viability were evaluated first, and then its effects on the cell cycle and the glycolytic process were analyzed by Western blots and specific assays. Possible MG-induced apoptosis was also assessed by DNA analysis using agarose gel electrophoresis.


RESULTS
MG > or =3 mM caused severe growth inhibition, resulting in nearly 100% cell death by 24h. The time course study revealed that expression of cyclin D(1), cdk2, and cdk4 was significantly (>50%) downregulated in 3 h of MG (3 mM) exposure, followed by the dephosphorylation of retinoblastoma protein by 6 h. Both the glyceraldehyde-3-phosphate dehydrogenase activity and the cellular lactate level were also reduced by approximately 50 and 80%, respectively, following 6-hour MG exposure. Induction of apoptosis by MG was indicated by partial degradation of poly(ADP-ribose) polymerase and further confirmed by discrete DNA fragmentation detected on an agarose gel.


CONCLUSIONS
MG is capable of inducing apoptosis in prostatic cancer PC-3 cells, 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.
Milanesa
D M
DM
Department of Urology, New York Medical College, Valhalla, NY 10595, USA.
Choudhury
M S
MS
Mallouh
C
C
Tazaki
H
H
Konno
S
S
D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy; D011765:Pyruvaldehyde / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D011765:Pyruvaldehyde