Resveratrol induces apoptosis of human malignant B cells by activation of caspase-3 and p38 MAP kinase pathways

Takayuki Shimizu, Tomonori Nakazato, Ming Ji Xian, Morihiko Sagawa, Yasuo Ikeda, Masahiro Kizaki

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73 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)742-750
Number of pages9
JournalBiochemical Pharmacology
Volume71
Issue number6
DOIs
Publication statusPublished - 2006 Mar 14

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Keywords

  • Apoptosis
  • B cell malignancy
  • Caspase
  • Myeloma
  • Resveratrol
  • p38 MAP kinase

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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