Effect of methylglyoxal on human leukaemia 60 cell growth: modification of DNA G1 growth arrest and induction of apoptosis

Abstract

Methylglyoxal induced growth arrest in the G1 phase of the cell cycle and toxicity in human leukaemia 60 cells in vitro. Inhibition of DNA synthesis but not inhibition of RNA synthesis, protein synthesis or inhibition of glyceraldehyde-3-phosphate dehydrogenase activity correlated with cytotoxicity. Incubation of human leukaemia 60 cells with methylglyoxal led to the rapid accumulation of adducts of methylglyoxal with DNA, and a lower accumulation of methylglyoxal adducts with RNA and protein in the initial hour of culture; fragmentation of nuclear DNA characteristic of apoptosis developed in the second hour of culture. Methylglyoxal induced apoptosis in human leukaemia 60 cells but did not affect the growth and viability of concanavalin A-stimulated human peripheral lymphocytes in vitro. These effects confirm and further substantiate the anti-proliferative anti-tumour activity of methylglyoxal in vitro, which may mediate the anti-tumour activity of glyoxalase I inhibitors in vivo.