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

Research output: Contribution to journalArticle

72 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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MAP Kinase Signaling System
p38 Mitogen-Activated Protein Kinases
Caspase 3
B-Lymphocytes
Chemical activation
Cells
Apoptosis
Cell Cycle Checkpoints
S Phase
Stilbenes
Phosphorylation
Wine
Automatic teller machines
Polyphenols
Proxy
Multiple Myeloma
Membrane Potentials
resveratrol
Tumors
Neoplasms

Keywords

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

ASJC Scopus subject areas

  • Pharmacology

Cite this

Resveratrol induces apoptosis of human malignant B cells by activation of caspase-3 and p38 MAP kinase pathways. / Shimizu, Takayuki; Nakazato, Tomonori; Xian, Ming Ji; Sagawa, Morihiko; Ikeda, Yasuo; Kizaki, Masahiro.

In: Biochemical Pharmacology, Vol. 71, No. 6, 14.03.2006, p. 742-750.

Research output: Contribution to journalArticle

Shimizu, Takayuki ; Nakazato, Tomonori ; Xian, Ming Ji ; Sagawa, Morihiko ; Ikeda, Yasuo ; Kizaki, Masahiro. / Resveratrol induces apoptosis of human malignant B cells by activation of caspase-3 and p38 MAP kinase pathways. In: Biochemical Pharmacology. 2006 ; Vol. 71, No. 6. pp. 742-750.
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