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TRAIL apoptosis is enhanced by quercetin through Akt dephosphorylation
Author(s) -
Kim YoungHo,
Lee Yong J.
Publication year - 2006
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21098
Subject(s) - apoptosis , protein kinase b , dephosphorylation , lncap , cancer cell , pi3k/akt/mtor pathway , quercetin , chemistry , cytotoxicity , cancer research , poly adp ribose polymerase , caspase 8 , phosphorylation , programmed cell death , microbiology and biotechnology , caspase , pharmacology , biology , biochemistry , cancer , in vitro , phosphatase , polymerase , gene , genetics , antioxidant
TNF‐related apoptosis‐inducing ligand (TRAIL) is a promising cancer therapy that preferentially induces apoptosis in cancer cells. However, many neoplasms are resistant to TRAIL by mechanisms that are poorly understood. Here we demonstrated that human prostate cancer cells, but not normal prostate cells, are dramatically sensitized to TRAIL‐induced apoptosis and caspase activation by quercetin. Quercetin, a ubiquitous bioactive plant flavonoid, has been shown to inhibit the proliferation of cancer cells. We have shown that quercetin can potentiate TRAIL‐induced apoptotic death. Human prostate adenocarcinoma DU‐145 and LNCaP cells were treated with various concentrations of TRAIL (10–200 ng/ml) and/or quercetin (10–200 µM) for 4 h. Quercetin, which caused no cytotoxicity by itself, promoted TRAIL‐induced apoptosis. The TRAIL‐mediated activation of caspase, and PARP (poly(ADP‐ribose) polymerase) cleavage were both enhanced by quercetin. Western blot analysis showed that combined treatment with TRAIL and quercetin did not change the levels of TRAIL receptors (death receptors DR4 and DR5, and DcR2 (decoy receptor 2)) or anti‐apoptotic proteins (FLICE‐inhibitory protein (FLIP), inhibitor of apoptosis (IAP), and Bcl‐2). However, quercetin promoted the dephosphorylation of Akt. Quercetin‐induced potent inhibition of Akt phosphorylation. Taken together, the present studies suggest that quercetin enhances TRAIL‐induced cytotoxicity by activating caspases and inhibiting phosphorylation of Akt. J. Cell. Biochem. 100: 998–1009, 2007. © 2006 Wiley‐Liss, Inc.