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.
Lieu
C H
CH
Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan, Republic of China.
Liu
C C
CC
Yu
T H
TH
Chen
K D
KD
Chang
Y N
YN
Lai
Y K
YK
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002469:Cell Separation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005057:Eukaryotic Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects / Q000502:physiology; D016195:G2 Phase / Q000187:drug effects / Q000502:physiology; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000473:pathology / Q000503:physiopathology*; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D008938:Mitosis / Q000187:drug effects / Q000502:physiology; D017239:Paclitaxel / Q000494:pharmacology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D016196:S Phase / Q000187:drug effects / Q000502:physiology; D014443:Tyrosine / Q000378:metabolism; D020298:U937 Cells
D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D014443:Tyrosine; C482128:MAP2K2 protein, human; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; C482125:MAP2K1 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases; D017239:Paclitaxel