title: Triptolide Induces Cell Apoptosis by Targeting H3K4me3 and Downstream Effector Proteins in KM3 Multiple Myeloma Cells.
abstract: As the principal active ingredient in the Chinese herb Tripterygium wilfordii Hook.F (TwHF), triptolide has been shown to have very strong antitumor properties. The trimethylation of lysine 4 on histone H3 (H3K4me3) has been proposed to promote gene expression, and the accumulation of H3K4me3 at the transcriptional start sites of oncogenes is involved in carcinogenesis. To identify the association between the reduction of H3K4me3 and the apoptosis of MM cells induced by triptolide, we investigated the global patterns of H3K4me3 occupancy in the MM cell genome. Combined analyses using ChIP-on-chip and western blotting showed that H3K4me3 were highly enriched on the gene promoters of c-Myc and VEGFA and were associated with the up-regulation of both genes. Treatment of KM3 cells with triptolide and siRNA targeting ASH2L reduced the expression of c-Myc and VEGFA. These results suggest that triptolide can down-regulate c-Myc and VEGFA expression by blocking the accumulation of H3K4me3 on their promoters,and thus play an important role in anti-MM mechanism.
authors.forename: Lu
authors.initials: L
authors.lastname: Wen
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Ling L
authors.initials: LL
authors.lastname: Zeng
authors.forename: Fei
authors.initials: F
authors.lastname: Zhao
authors.forename: Sha
authors.initials: S
authors.lastname: Yi
authors.forename: Li J
authors.initials: LJ
authors.lastname: Yang
authors.forename: Ben P
authors.initials: BP
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
authors.forename: Zi C
authors.initials: ZC
authors.lastname: Zhao
authors.affiliation: 1277 Jiefang Avenue, Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei Province, China. zhangchun0523@163.com.
authors.forename: Chun
authors.initials: C
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D009101:Multiple Myeloma / Q000473:pathology*; D010616:Phenanthrenes / Q000494:pharmacology*
chemical_list: D004224:Diterpenes; D004852:Epoxy Compounds; D006657:Histones; D010616:Phenanthrenes; C001899:triptolide