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PKC and MEK pathways inhibit caspase‐9/‐3‐mediated cytotoxicity in differentiated cells
Author(s) -
Yiang Giou-Teng,
Yu Yung-Luen,
Hu Sheng-Chuan,
Chen Mark Hung-Chih,
Wang Jaang-Jiun,
Wei Chyou-Wei
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.02.018
Subject(s) - cytotoxicity , protein kinase c , chemistry , caspase , microbiology and biotechnology , apoptosis , protein kinase a , cellular differentiation , kinase , biology , programmed cell death , biochemistry , in vitro , gene
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.