title: [Mechanism of As(2)O(3) on hdpr1 gene demethylation in Jurkat cell line].
abstract: This study was purposed to investigate the effect of As(2)O(3) on the demethylation of anti-oncogene-hdpr1 gene of acute lymphoblastic leukemia cell line Jurkat in vitro and its mechanism. The inhibitory effect of As(2)O(3) on the proliferation of Jurkat cells was assayed by CCK-8; the change of Jurkat cell cycle was detected by flow cytometry before and after using As(2)O(3); the effect of As(2)O(3) on the methylation model of hdpr1 gene was analyzed by methylation-specific PCR, and the effect of As(2)O(3) on the expression of hdpr1 mRNA was analyzed by semiquantitative RT-PCR. The results showed that the proliferation rate of Jurkat cells was decreased significantly after being treated with As(2)O(3), and in dose-and time-dependent manner; As(2)O(3) blocked Jurkat cell cycle in G(0)/G(1) phase in dose-dependent manner. As(2)O(3) could reverse hypermethylation of hdpr1 gene and induce its mRNA reexpression, and down-regulate the dnmt1, dnmt3a, dnmt3b mRNA expression level also in dose-dependent manner. It is concluded that the As(2)O(3) suppresses the proliferation of Jurkat cells and blocks cell cycle is G(0)/G(1), its possible mechanism may be down-regulating mRNA expression level of dnmt1, dnmt3a and dnmt3b, induce demethylation of hdpr1 gene from abnormal hypermethylation status and activates its reexpression.
authors.affiliation: Fujian Institute of Hematology, Fujian Medical University, Fuzhou 350001, Fujiang Province, China.
authors.forename: Song-Fei
authors.initials: SF
authors.lastname: Shen
authors.forename: Jian-Zhen
authors.initials: JZ
authors.lastname: Shen
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Fu
authors.forename: Dan-Sen
authors.initials: DS
authors.lastname: Wu
authors.forename: Chen-Bo
authors.initials: CB
authors.lastname: Xu
authors.forename: Yi-Fang
authors.initials: YF
authors.lastname: Zhu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects*; D016147:Genes, Tumor Suppressor; D006801:Humans; D019169:Jurkat Cells; D009687:Nuclear Proteins / Q000235:genetics*; D010087:Oxides / Q000494:pharmacology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001152:Arsenicals; C491683:DACT1 protein, human; D009687:Nuclear Proteins; D010087:Oxides; D000077237:Arsenic Trioxide