ROLE OF MITOGEN-ACTIVATED PROTEIN-KINASE IN TAXOL-INDUCED APOPTOSIS IN HUMAN LEUKEMIC U937 CELLS

The induction of apoptosis by Taxol was investigated in human leukemic U937 cells. Treatment of U937 cells with 20 nM Taxol for 24 h induced apoptosis in 30-40% of cells, which resulted in an 80% growth inhibit ion 3 days after treatment. Synchronous cells at different cell cycle stages exhibited different sensitivities toward Taxol, and their rever sion by certain protein kinase inhibitors was also phase specific. Kin etic studies of cell cycle progress reveal that Taxol accelerates the progression of the cell cycle, which facilitates the process of apopto sis, especially for cells initially in the G(1) phase. This accelerati on may result from transient activation of p42/44 mitogen-activated pr otein (MAP) kinase, because inhibition of upstream MAP/extracellular s ignal-regulated kinase kinase (MEK1/2) by PD98059 reversed this effect . However, the delayed S-G(2)-M-phase progression by PD98059 was insig nificant. The results suggest that MAP kinase may not only mediate cel l cycle progress but may also participate in the apoptosis pathway for cells originally in S phase.