title: 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.affiliation: Department of Orthopedics, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Shing-Sheng
authors.initials: SS
authors.lastname: Wu
authors.forename: Lih-Geeng
authors.initials: LG
authors.lastname: Chen
authors.forename: Ren-Jye
authors.initials: RJ
authors.lastname: Lin
authors.forename: Shyr-Yi
authors.initials: SY
authors.lastname: Lin
authors.forename: Yueh-E
authors.initials: YE
authors.lastname: Lo
authors.forename: Yu-Chih
authors.initials: YC
authors.lastname: Liang
mesh_terms: D000970:Antineoplastic Agents / Q000032:analysis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins; D001572:Benzofurans / Q000032:analysis / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000473:pathology; D008518:Medicine, East Asian Traditional; D010636:Phenols / Q000032:analysis / Q000494:pharmacology*; D010936:Plant Extracts / Q000032:analysis / Q000494:pharmacology; D013624:Taiwan; D027843:Vitis / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D001572:Benzofurans; D010636:Phenols; D010936:Plant Extracts; C480486:malvidin-3-O-glucoside-4 vinyl