title: Thallium acetate induces C6 glioma cell apoptosis.
abstract: Thallium acetate is a known neurotoxic agent. In this study, we investigated the mechanisms by which thallium acetate induces cell cycle arrest and cell apoptosis in cultured LC6 glioma cells. Exposure of C6 glioma cells to thallium acetate decreased cell viability as demonstrated by the MTT assay. Incubation of thallium acetate arrested cell cycle progression at the G2/M phase and caused cellular apoptosis at 300 microM as determined by trypan blue exclusion and flow cytometric analysis. The G2/M arrest was associated with a decrease in expression of CDK2 protein and an upregulation of p53 and the CDK inhibitor p21(Cip1), but not p27(Kip1). Thallium acetate did not alter the protein levels of cyclin A and B; cyclin D1, D2, and D3; and CDK4 expression in C6 glioma cells. Incubation of C6 glioma cells with thallium acetate upregulated the expression of proapoptotic proteins Bad and Apaf and downregulated the expression of anti-apoptotic proteins Bcl-xL and Bcl-2. In conclusion, these data suggest that thallium acetate inhibits cell cycle progression at G2/M phase by suppressing CDK activity through the p53-mediated induction of the CDK inhibitor p21(Cip1). Impairment of cell cycle progression may trigger the activation of a mitochondrial pathway and shifts the balance in the Bcl-2 family toward the proapoptotic members, promoting the formation of the apoptosome and, consequently, apoptosis.
authors.affiliation: Department of Surgery, School of Medicine, Taipei Medical University and Hospital, 252 Wu-Hsing St., Taipei, Taiwan.
authors.forename: Chee-Fah
authors.initials: CF
authors.lastname: Chia
authors.forename: Soul-Chin
authors.initials: SC
authors.lastname: Chen
authors.forename: Chin-Shyang
authors.initials: CS
authors.lastname: Chen
authors.forename: Chuen-Ming
authors.initials: CM
authors.lastname: Shih
authors.forename: Horng-Mo
authors.initials: HM
authors.lastname: Lee
authors.forename: Chih-Hsiung
authors.initials: CH
authors.lastname: Wu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D009942:Organometallic Compounds / Q000494:pharmacology*; D051381:Rats
chemical_list: D018797:Cell Cycle Proteins; D009942:Organometallic Compounds; C026995:thallium acetate