Overexpression of glyoxalase system enzymes in human kidney tumor

PURPOSE: The purpose of this study was to investigate the messenger RNA expression and activity of glyoxalase I and glyoxalase 11 enzymes in a human renal carcinoma (clear cell adenocarcinoma) and in pair-matched normal tissue. PATIENTS AND METHODS: Tumor and nontumor pair-matched specimens from the same organ were collected during radical nephrectomy from a group of 12 patients of both sexes. The mean age of the patients was 52.3 years (range, 50-60 years), and none of them had previously undergone neoadjuvant therapy. Gene expression and activity were measured by ribonuclease protection assay and current spectrophotometric methods, respectively. Intracellular levels of methylglyoxal were detected by high performance liquid chromatography. RESULTS: A significant increase in the transcription levels of both glyoxalase I (about ninefold) and glyoxalase 11 (about threefold) was observed, compared with the pair-matched noncancerous tissues. Glyoxalase I activity was also higher in the pathological samples (about 2.5-fold) compared with the control samples and correlated with a significant decrease (about twofold) in methylglyoxal concentrations. At variance, glyoxalase 11 activity was significantly lower in pathological tissues than in the normal ones. DISCUSSION: Our findings suggest a possible role of the glyoxalase system enzymes in the chemoresistance displayed by the kidney tumor. In fact, such a refractory behavior involves a decrease in the methylglyoxal level, a potent apoptosis activator. In addition, glyoxalase 11 activity decrease in the adenocarcinoma tissue suggests a likely role of the intermediate S-D-lactoylglutathione by supplying energy in actively proliferating cells. Finally, we point out a possible use of glyoxalase I inhibitors as anticancer drugs.