Apoptosis and mitotic arrest are two independent effects of the protein phosphatases inhibitor okadaic acid in K562 leukemia cells

Treatment of human myeloid leukemia K562 cells with the serine/threonine pr otein phosphatases inhibitor okadaic acid induced mitotic arrest followed b y apoptosis in a synchronized manner. The effect was observed at drug conce ntrations that inhibited the protein phosphatase type 2A but not type 1. We investigated whether apoptosis was a consequence of the preceding mitosis arrest or was induced independently by okadaic acid. We found that (1) apop tosis, but not mitotic arrest, was inhibited in cells with constitutive exp ression of Bcl-2; (2) pretreatment of cells with the DNA synthesis inhibito r hydroxyurea blocked the mitotic arrest but not the apoptosis mediated by okadaic acid; (3) down-regulation of c-myc gene was associated with apoptos is, but not with mitotic arrest; and (4) inhibition of protein synthesis ab rogated mitotic arrest, but not apoptosis. The results suggest that inhibit ion of protein phosphatase 2A by okadaic acid provokes mitotic arrest and a poptosis of leukemia cells by independent mechanisms; (C) 1999 Academic Pre ss.