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Michael adducts of ascorbic acid as inhibitors of protein phosphatase 2A and inducers of apoptosis |
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| Authors: | Fathi A R Krautheim A Kaap S Eger K Steinfelder H J |
| Institution: | 1. Faculty of Science, Charles University in Prague, 12843 Prague, Czech Republic;2. Institute of Physiology, Academy of Sciences of the Czech Republic, 14220 Prague, Czech Republic;3. Institute of Microbiology, Academy of Sciences of the Czech Republic, 14220 Prague, Czech Republic;4. Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 16610 Prague, Czech Republic;5. Faculty of Science, Palacky University, 78341 Olomouc, Czech Republic;6. 3rd Faculty of Medicine, Charles University in Prague, 10000 Prague, Czech Republic;7. 2nd Faculty of Medicine, Charles University in Prague, 15006 Prague, Czech Republic |
| Abstract: | Michael adducts of ascorbic acid with alpha,beta-unsaturated carbonyl compounds have been shown to be potent inhibitors of protein phosphatase 1 (PP1) without affecting cell viability at the respective concentrations. Here we were able to show that higher concentrations can partially inhibit PP2A activity and concomitantly induce apoptotic cell death. A nitrostyrene adduct of ascorbic acid proved to be a more potent and effective inhibitor of PP2A as well as a stronger inducer of apoptosis. These adducts only slightly lost their cytotoxic potential in multidrug resistant cells that were 10-fold less sensitive to apoptosis induction by okadaic acid and vinblastine. |
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