Role of Glyoxalase I in the proliferation and apoptosis control of human LNCaP and PC3 prostate cancer cells.

Glyoxalase I (GLOI) detoxifies reactive dicarbonyls, as methylglyoxal (MG) that, directly or through the formation of MG-derived adducts, is a growth inhibitor and apoptosis inducer. GLOI has been considered a general marker of cell proliferation, but a direct link between the two has yet to be demonstrated. The aim of the present work was to clarify whether GLOI was involved in the proliferation control of LNCaP and PC3 human prostate cancer cells or might play a different role in the growth regulation of these cells. RNA interference was used to study the role of GLOI in cell proliferation or apoptosis. Cell proliferation was evaluated by [3H]thymidine incorporation assay and flow cytometry, that was also used to analyze apoptosis. Real time TaqMan polymerase chain reaction and spectrophotometric analyses were used to study transcript levels or specific activity, respectively. Proteins levels were analyzed by western blot. Methylglyoxal was measured by high performance liquid chromatography. We found that GLOI is not implicated in the proliferation control of LNCaP and PC3 cells but plays a role in the apoptosis of invasive prostate cancer PC3 cells, through a mechanism involving a specific MG-adduct and mediated by NF-kB signaling pathway. GLOI silencing inhibited constitutive NF-kB activity, which was consistent with down-regulation of NF-kB-regulated genes. Our data represent the first systematic demonstration that GLOI cannot be considered a general marker of cell proliferation and that may act as a pro-survival factor in invasive PC3 cells by elusing apoptosis. Our results suggest that GLOI may play a crucial role in the progression of prostate cancer.