Michael adducts of ascorbic acid as inhibitors of protein phosphatase 2A and inducers of apoptosis

Michael adducts of ascorbic acid with alpha,beta-unsaturated carbonyl compo unds have been shown to be potent inhibitors of protein phosphatase 1 (PPI) without affecting cell viability at the respective concentrations. Here we were able to show that higher concentrations can partially inhibit PP2A ac tivity and concomitantly induce apoptotic cell death. A nitrostyrene adduct of ascorbic acid proved to be a more potent and effective inhibitor of PP2 A as well as a stronger inducer of apoptosis. These adducts only slightly l ost their cytotoxic potential in multidrug resistant cells that were 10-fol d less sensitive to apoptosis induction by okadaic acid and vinblastine. (C ) 2000 Elsevier Science Ltd. All rights reserved.