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Acta Biochimica et Biophysica Sinica Advance Access published online on November 10, 2009
Acta Biochimica et Biophysica Sinica, doi:10.1093/abbs/gmp094
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© The Author 2009. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

Potentiation of (–)-epigallocatechin-3-gallate-induced apoptosis by bortezomib in multiple myeloma cells

Qing Wang, Juan Li*, Jingli Gu, Beihui Huang, Ying Zhao, Dong Zheng, Yan Ding and Lijin Zeng

Department of Hematology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China

* Correspondence address. Tel: +86-20-87755766-8831; Fax: +86-20-87333455; E-mail: luliyuan{at}tom.com


  Abstract

The green tea constituent, (–)-epigallocatechin-3-gallate (EGCG), has chemopreventive and anticancer effects. This is partially because of the selective ability of EGCG to induce apoptosis and death in cancer cells without affecting normal cells. In the present study, the activity of EGCG against the myeloma cell line, KM3, was examined. Our results demonstrated, for the first time, that the treatment of the KM3 cell line with EGCG inhibits cell proliferation and induces apoptosis, and there is a synergistic effect when EGCG and bortezomib are combined. Further experiments showed that this effect involves the NF-{kappa}B pathway. EGCG inhibits the expression of the P65 mRNA and P65/pP65 protein, meanwhile it downregulates pI{kappa}B{alpha} expression and upregulates I{kappa}B{alpha} expression. EGCG also activates caspase-3, -8, cleaved caspase-9, and poly-ADP-ribose polymerase (PARP) and subsequent apoptosis. These findings provided experimental evidence for efficacy of EGCG alone or in combination with bortezomib in multiple myeloma therapy.

Keywords    (–)-epigallocatechin-3-gallate; apoptosis; NF-{kappa}B; bortezomib; multiple myeloma

Received: May 11, 2009; Accepted: August 7, 2009
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