Triphenyl Tin Benzimidazolethiol, a Novel Antitumor Agent, Induces Mitochondrial-Mediated Apoptosis in Human Cervical Cancer Cells via Suppression of HPV-18 Encoded E 6

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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 E 6, restoring p 53 expression from E 6 suppression. Increased p 53 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.
社団法人日本生化学会の論文