Methylglyoxal is a reactive dicarbonyl compound endogenously produced mainly from glycolytic intermediates. Recent research indicates that
methylglyoxal is a potent
growth inhibitor and genotoxic agent. The antiproliferative activity of
methylglyoxal has been investigated for pharmacological application in
cancer chemotherapy. However, various cells are not equally sensitive to
methylglyoxal toxicity. Therefore, it would be important to establish the cellular factors responsible for the different cell-type specific response to
methylglyoxal injury, in order to avoid the risk of failure of a
therapy based on increasing the intracellular level of
methylglyoxal. To this purpose, we comparatively evaluated the signaling transduction pathway elicited by
methylglyoxal in human
glioblastoma (ADF) and
neuroblastoma (SH-SY 5Y) cells. Results show that
methylglyoxal causes early and extensive
reactive oxygen species generation in both cell lines. However, SH-SY 5Y cells show higher sensitivity to
methylglyoxal challenge due to a defective
antioxidant and detoxifying ability that, preventing these cells from an efficient scavenging action, elicits extensive
caspase-9 dependent apoptosis. These data emphasize the pivotal role of
antioxidant and detoxifying systems in determining the grade of sensitivity of cells to
methylglyoxal.