title: Triphenyl tin benzimidazolethiol, a novel antitumor agent, induces mitochondrial-mediated apoptosis in human cervical cancer cells via suppression of HPV-18 encoded E6.
abstract: Here we report the effect of TPT-benzimidazolethiol, a novel anti-tumor agent developed by our group, on the apoptotic pathway of human cervical carcinoma cells. Treatment of HeLa cells with TPT-benzimidazolethiol arrests the cell cycle at G0/G1 phase and transcriptionally downregulates HPV-encoded E6, restoring p53 expression from E6 suppression. Increased p53 accumulation up-regulates p21/waf and ultimately induces apoptosis. The effect of TPT-benzimidazolethiol is far more potent in inducing apoptosis than cisplatin. Treatment with TPT-benzimidazolethiol in HeLa cells is accompanied by the up-regulation of Bak at the transcriptional level, resulting in the release of cytochrome c and Smac/DIABLO from mitochondria to cytosol and, subsequently, the activation of procaspase-9, -3 and PARP, suggesting that TPT-benzimidazolethiol induced-apoptosis signaling is by an intrinsic mitochondrial pathway. Taken together, we propose that TPT-benzimidazolethiol could has the potential to be developed into a new therapeutic agent for treating HPV-associated cervical neoplasia.
authors: Department of Molecular and Cell Biology, Key Laboratory of Structural Biology, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230027, People's Republic of China.
authors: Naseruddin
authors: N
authors: Höti
authors: Jun
authors: J
authors: Ma
authors: Sartaj
authors: S
authors: Tabassum
authors: Yi
authors: Y
authors: Wang
authors: Mian
authors: M
authors: Wu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001562:Benzimidazoles / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002469:Cell Separation; D004247:DNA / Q000737:chemistry; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000494:pharmacology; D016193:G1 Phase; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology*; D008956:Models, Chemical; D009841:Oligonucleotides / Q000737:chemistry / Q000494:pharmacology; D009947:Organotin Compounds / Q000737:chemistry / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D016192:Resting Phase, Cell Cycle; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D050998:bcl-2 Homologous Antagonist-Killer Protein
chemical_list: D000970:Antineoplastic Agents; C494772:BAK1 protein, human; D001562:Benzimidazoles; D005456:Fluorescent Dyes; D008565:Membrane Proteins; D009841:Oligonucleotides; D009947:Organotin Compounds; D013778:Tetrazolium Salts; D013844:Thiazoles; D016159:Tumor Suppressor Protein p53; D050998:bcl-2 Homologous Antagonist-Killer Protein; C490337:triphenyl tin benzimidazolethiol; D004247:DNA; C030665:triphenyltin; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases; C022616:thiazolyl blue