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 inhibition 3 days after treatment. Synchronous cells at different cell cycle stages exhibited different sensitivities toward Taxol, and their reversion by certain protein kinase inhibitors was also phase specific. Kinetic studies of cell cycle progress reveal that Taxol accelerates the progression of the cell cycle, which facilitates the process of apoptosis, especially for cells initially in the G₁ phase. This acceleration may result from transient activation of p42/44 mitogen-activated protein (MAP) kinase, because inhibition of upstream MAP/extracellular signal-regulated kinase kinase (MEK1/2) by PD98059 reversed this effect. However, the delayed S-G₂-M-phase progression by PD98059 was insignificant. The results suggest that MAP kinase may not only mediate cell cycle progress but may also participate in the apoptosis pathway for cells originally in S phase.