title: Discovery of polyoxometalate-based HDAC inhibitors with profound anticancer activity in vitro and in vivo.
abstract: We obtained 5 positive novel histone deacetylase inhibitors (HDACIs) from a polyoxometalate (POM) library by using a cell-based screening system targeting the p21 gene promoter. Among them, PAC-320, a new tri-organic-tin-substitute germanotungstate, displayed remarkable extracellular inhibitory activity. Meanwhile, the crystal structure of PAC-320 was characterized by X-ray crystallography. PAC-320 could stably exist under physiological conditions as revealed by UV spectrum, CV and TG. PAC-320 possessed a strong inhibitory effect to intracellular HDAC activity. More significantly, PAC-320 inhibited the growth of a variety of cancer cells, and exhibited remarkable anticancer effect in a hepatocarcinoma H22 cell mice model. This study revealed, for the first time, that the HDAC inhibitory activity is a mechanism by which POMs exert their anticancer effect.
authors.affiliation: Institute of Genetics and Cytology, The Key Laboratory of Molecular Epigenetic of Ministry of Education (MOE), Northeast Normal University, Changchun 130024, China.
authors.forename: Zhixiong
authors.initials: Z
authors.lastname: Dong
authors.forename: Ruikang
authors.initials: R
authors.lastname: Tan
authors.forename: Jian
authors.initials: J
authors.lastname: Cao
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Chenfei
authors.initials: C
authors.lastname: Kong
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.forename: Shan
authors.initials: S
authors.lastname: Zhu
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.forename: Baiqu
authors.initials: B
authors.lastname: Huang
authors.forename: Shuxia
authors.initials: S
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D017973:Tungsten Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000099294:Polyoxometalates
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D017973:Tungsten Compounds; C102296:polyoxometalate I; D000099294:Polyoxometalates