Cytotoxicity of (-)-vitisin B in human leukemia cells. (July 2013)

• Record Type: Journal Article
• Authors: Wu, Shing-Sheng; Chen, Lih-Geeng; Lin, Ren-Jye; Lin, Shyr-Yi; Lo, Yueh-E; Liang, Yu-Chih
• Is Part Of: Drug and chemical toxicology. Volume 36:Number 3(2013:Jul.)
• Page Start: 313
• Page End: 319
• Publication Date: 2013-07
• Subjects: Vitis thunbergii var. taiwaniana -- (-)-vitisin B -- leukemia -- apoptosis -- Fas ligand -- JNK; Toxicology -- Periodicals; Drugs -- Toxicology -- Periodicals; Toxicology, Experimental -- Periodicals; 615.9005
• DOI: 10.3109/01480545.2012.720990
• Languages: English
• ISSNs: 0148-0545

Abstract

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.