Cytotoxicity of (-)-vitisin B in human leukemia cells.

Abstract

Vitis thunbergii var. taiwaniana (VTT) is an indigenous Taiwanese wild grape and is used as a folk medicine in Taiwan. VTT is rich in polyphenols, especially quercetin and resveratrol derivatives, which were demonstrated to exhibit inhibitory activities against carcinogenesis and prevent some neurodegenerative diseases. (-)-Vitisin B is one of the resveratrol tetramers extracted from VTT. In this study, we investigated the mechanisms of (-)-vitisin B on the induction of apoptosis in human HL-60 promyelocytic leukemia cells. First, (-)-vitisin B significantly inhibited cell proliferation through inducing cell apoptosis. This effect appeared to occur in a time- and dose-dependent manner. Cell-cycle distribution was also examined, and we found that (-)-vitisin B significantly induced a sub-G1 population in a dose-dependent manner. In addition, (-)-vitisin B exhibited stronger inhibitory effects on cell proliferation than resveratrol. Second, (-)-vitisin B dose dependently induced apoptosis-related protein expressions, such as the cleavage form of caspase-3, caspase-8, caspase-9, poly(ADP ribose) polymerase, and the proapoptotic Bax protein. Third, (-)-vitisin B treatment also resulted in increases in c-Jun N-terminal kinase (JNK) phosphorylation and Fas ligand (FasL) expression. Moreover, the (-)-vitisin B-induced FasL expression and caspase-3 activation could be reversed by a JNK inhibitor. These results suggest that (-)-vitisin B-induced apoptosis of leukemia cells might be mediated through activation of JNK and Fas death-signal transduction.

• Authors: Shing-Sheng Wu, Lih-Geeng Chen, Ren-Jye Lin, Shyr-Yi Lin, Yueh-E Lo, Yu-Chih Liang
• Journal: Drug and chemical toxicology (Drug Chem Toxicol) Vol. 36 Issue 3 Pg. 313-9 (Jul 2013) ISSN: 1525-6014 [Electronic] United States
• PMID: 23030068 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Apoptosis Regulatory Proteins
• Benzofurans
• Phenols
• Plant Extracts
• malvidin-3-O-glucoside-4 vinyl

Topics

• Antineoplastic Agents (analysis, pharmacology)
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins
• Benzofurans (analysis, pharmacology)
• Cell Cycle (drug effects)
• Cell Survival (drug effects)
• Chromatography, High Pressure Liquid
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• HL-60 Cells
• Humans
• Leukemia, Promyelocytic, Acute (drug therapy, pathology)
• Medicine, East Asian Traditional
• Phenols (analysis, pharmacology)
• Plant Extracts (analysis, pharmacology)
• Taiwan
• Vitis (chemistry)