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Curcumin induces apoptosis by suppressing protein phosphatase 5 leading to activation of JNK cascade
Author(s) -
Huang Shile,
Han Xiuzhen,
Xu Baoshan
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.943.11
Subject(s) - curcumin , apoptosis , kinase , phosphatase , chemistry , phosphorylation , microbiology and biotechnology , downregulation and upregulation , regulator , programmed cell death , cancer research , c jun , biochemistry , biology , transcription factor , gene
Curcumin (diferuloylmethane), a polyphenol natural product of the plant Curcuma longa, is undergoing early clinical trials as a novel anticancer agent. However, the anticancer mechanism of curcumin remains to be elucidated. Our recent studies indicate that curcumin induces apoptosis of cancer cells. This study was set to investigate the underlying mechanism. Here we show that treatment of human cancer cells (Rh30 and HT29) with curcumin activated JNK cascade. This is evidenced by the findings that curcumin increased phosphoryaltion of MKK4 (an upstream kinase of JNK), JNK and c‐Jun (a substrate of JNK). Inhibition of JNK with SP600125 partially prevented curcumin‐induced apoptosis. Similarly, overexpression of dominant negative c‐Jun or downregulation of c‐Jun also in part attenuated curcumin‐induced cell death. Furthermore, we found that curcumin inhibited the activity of protein phosphatase 5 (PP5), a negative regulator of JNK pathway. Overexpression of PP5 blocked curcumin‐induced phosphorylation of c‐Jun and apoptosis. The results suggest that curcumin induced apoptosis through inhibition of PP5, resulting in activation of JNK pathway.