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.

Alteration of glyoxalases gene expression in response to testosterone in LNCaP and PC3 human prostate cancer cells

“…9,10 Abnormal expression of this system has been demonstrated in a number of cellular disorders, including cancer. [11][12][13][14][15] In particular, altered expression and activities of GI and GII have been documented in tumor urogenital tissues [12][13][14][15][16][17] and in prostate tumor cell lines compared with corresponding normal tissues. 18 These alterations are considered to be crucial for sustaining tumor viability/survival under an altering microenvironment with tumor growth.…”

Glyoxalase I Is Critical for Human Retinal Capillary Pericyte Survival under Hyperglycemic Conditions

“…Work by Shinohara et al (28) demonstrated that overexpression of glyoxalase I in bovine endothelial cells reduced intracellular AGEs when the cells were cultured in the presence of high glucose. In addition, a series of studies indicated that certain tumor primary cultures and cell lines overexpress glyoxalase I (29,30), suggesting that increased amounts of this enzyme prevent tumor cell apoptosis (31), possibly by limiting MGO production. These findings spurred us to determine whether impaired function of glyoxalase I could result in HRP apoptosis in diabetes.…”

DNA Replication and Telomere Shortening: Key Factors Related to the Production of C3-Aldehydes and the Interaction of One of them with DNA Guanine Residues

“…MG presents in cancer cells in minimal quantities if present at all. For that reason, Gl-I may play a critical role in the viability of prostatic cancer cells: its activity is more than eightfold higher in prostate cancer specimens than in noncancerous specimens [32]. According to Watson [33], even though we will soon have comprehensive views on how most cancers arise and function at the genetic and biochemical levels, their 'curing' seems now to many seasoned scientists a daunting objective.…”