Resveratrol induces apoptosis of human malignant B cells by activation of caspase-3 and p38 MAP kinase pathways
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- 作者：Takayuki Shimizu ; Tomonori Nakazato ; Ming Ji Xian ; Morihiko Sagawa ; Yasuo Ikeda and Masahiro Kizaki
- 关键词：Resveratrol ; B cell malignancy ; Myeloma ; Apoptosis ; Caspase ; p38 MAP kinase
- 刊名：Biochemical Pharmacology
- 出版年：2006
- 出版时间：14 March 2006
- 年：2006
- 卷：71
- 期：6
- 页码：742-750
- 全文大小：666 K
文摘
Red wine polyphenol, trans-resveratrol (trans-3,4′,5-trihydroxy stilbene), has potent chemopreventive effects against various tumors. In this study, we found for the first time that resveratrol rapidly induces S phase cell cycle arrest of human malignant B cells including myeloma cells in dose- and time-dependent manners, followed by S phase cell cycle arrest through ATM/Chk pathway. Resveratrol-induced apoptosis occurs in association with the activation of caspase-3 and the loss of mitochondrial transmembrane potentials. In addition, resveratrol induces the phosphorylation of p38 MAP kinase, and specific inhibition of p38 MAP kinase abolishes the resveratrol-induced apoptosis, indicating that activation of the p38 MAP kinase pathway is required for inducing apoptosis in malignant B cells. These results suggest that resveratrol may have potential as a novel therapeutic agent for the patients with B cell malignancies including multiple myeloma.