A possible regulatory role of glyoxalase I in cell viability of human prostate cancer.
A role of glyoxalase I (Gly-I), a detoxifying enzyme, in cell viability of prostate cancer was investigated. Cell extracts obtained from 66 prostate tissue specimens and prostatic cancer PC-3 cells were assayed for Gly-I activity using the spectrophotometric method. Gly-I activity was consistently more than eightfold higher in prostate cancer (CAP) specimens (n = 37) than in non-cancerous (NCP) specimens (n = 29). To understand the importance of such a high Gly-I activity in CAP specimens, the effects of methylglyoxal (MG) on PC-3 cells were examined in vitro. MG, a putative toxic glycolytic metabolite, was capable of inducing severe (> 99%) cell death in 24 h, along with a significant reduction in activities of Gly-I as well as glyceraldehyde 3-phosphate dehydrogenase (G3PDH), a key glycolytic enzyme. However, such severe cell death was effectively (approximately 85%) prevented with N-acetylcysteine (NAC), a precursor of reduced glutathione (GSH) that is an essential cofactor for Gly-I, accompanied by the intact Gly-I and G3PDH activities. Therefore, Gly-I may play a critical detoxifying role in glycolysis to maintain cellular activity and viability of prostatic cancer cells.
Davidson
Scott D
SD
Department of Urology, New York Medical College, Valhalla 10595, USA.
Milanesa
Dan M
DM
Mallouh
Camille
C
Choudhury
Muhammad S
MS
Tazaki
Hiroshi
H
Konno
Sensuke
S
D000111:Acetylcysteine / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000037:antagonists & inhibitors; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007791:Lactoylglutathione Lyase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D011471:Prostatic Neoplasms / Q000503:physiopathology*; D011765:Pyruvaldehyde / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D011765:Pyruvaldehyde; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D007791:Lactoylglutathione Lyase; D000111:Acetylcysteine