PKC and MEK pathways inhibit caspase-9/-3-mediated cytotoxicity in differentiated cells.
Many studies have indicated that differentiated cells inhibit drug-induced cytotoxicity but undifferentiated cells do not, though the mechanisms are unclear. Currently, HL-60 cells are induced to differentiate into macrophage-like cells with Phorbol-12-myristate-13-acetate (TPA) treatment (TPA-differentiated cells). Our study shows that caspase-9/-3-mediated cytotoxicity can be induced in undifferentiated HL-60 cells but not in TPA-differentiated HL-60 cells. However, caspase-9/-3-mediated cytotoxicity can be induced in TPA-differentiated cells if they are pretreated with a protein kinase C (PKC) or a mitogen activated protein kinase (MEK) inhibitor. Taken together, this study demonstrates that TPA-differentiated HL-60 cells inhibit caspases-9/-3-mediated cytotoxicity through the PKC and MEK signaling pathways.
Yiang
Giou-Teng
GT
Institute of Medical Sciences, Tzu-Chi University, Hualien, Taiwan.
Yu
Yung-Luen
YL
Hu
Sheng-Chuan
SC
Chen
Mark Hung-Chih
MH
Wang
Jaang-Jiun
JJ
Wei
Chyou-Wei
CW
D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D061945:Caspase Inhibitors; D002454:Cell Differentiation; D004789:Enzyme Activation; D018922:HL-60 Cells; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology
D061945:Caspase Inhibitors; C016658:phorbolol myristate acetate; D011493:Protein Kinase C; D020929:Mitogen-Activated Protein Kinase Kinases; D053148:Caspase 3; D053453:Caspase 9; D013755:Tetradecanoylphorbol Acetate