Suppression of Cell-cycle Progression during the S Phase of Rat Fibroblasts by 3-Deoxyglucosone, a Maillard Reaction Intermediate

Abstract

3-Deoxyglucosone (3DG), the main intermediate compound in the Maillard reaction of proteins with glucose, suppressed the proliferation of various cell lines by inhibition of DNA synthesis. We investigated the mechanism of the suppression of cell proliferation from the standpoint of the progression of cell cycle. When 3DG was added to the culture of 3Y1 cells, rat fibroblasts, growing in exponential phase, the addition of 300 or 600μg/ml of 3DG increased the numbers of the cells apparently arrested at the G1 or G2/M phase, respectively. We observed that 3DG specifically inhibited the time-dependent progression during the S phase of a synchronous culture released from the early S phase in 3Y1 cells. 3DG influenced the cells released from the G0 phase but not the G0-arrested cells. When an intracellular concentration of reduced glutathione (GSH) in 3Y1 cells was decreased by using a GSH synthetase inhibitor, the inhibition of [³H]thymidine incorporation by 3DG was enhanced. Therefore, we assumed that the cells proliferating actively, in which the intracellular GSH concentrations have been reported to be lower, were more susceptible to the inhibitory effects of 3DG on the cell-cycle progression during the S phase.