title: A possible regulatory role of glyoxalase I in cell viability of human prostate cancer.
abstract: 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.
authors.affiliation: Department of Urology, New York Medical College, Valhalla 10595, USA.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Davidson
authors.forename: Dan M
authors.initials: DM
authors.lastname: Milanesa
authors.forename: Camille
authors.initials: C
authors.lastname: Mallouh
authors.forename: Muhammad S
authors.initials: MS
authors.lastname: Choudhury
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tazaki
authors.forename: Sensuke
authors.initials: S
authors.lastname: Konno
mesh_terms: 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
chemical_list: D004791:Enzyme Inhibitors; D011765:Pyruvaldehyde; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D007791:Lactoylglutathione Lyase; D000111:Acetylcysteine