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- W1988833132 abstract "Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DCPolymerization and de-polymerization of microtubule are responsible for separation of chromosomes during cell division which has been considered to be one of major targets in cancer chemotherapy. In order to develop a newer generation of chemotherapeutic agents with higher efficacy and lower toxicity, a novel microtubule-binding agent (AD1), an analog of thiocolchicine, has been successfully synthesized. We here demonstrated AD1 could effectively kill a panel of seven human hepatocellular carcinoma (HCC) cell lines with varying degrees of differentiation. The IC50 values for all these HCC cell lines, using NCI standard protocol (sulforhodamine B, SRB), ranged from 2 to 50 nM. Cell cycle analysis study by flowcytometer unveiled that AD1 could evoke a dose-dependent cell cycle arrest in the G2/M phase. Further immunoflurorescence studies revealed that AD1 could also disrupt tubulin polymerization which would be responsible for the G2/M arrest. These prominent events provoked the disruption of cellular microtubule networks and prevented the proper formation of spindle apparatus and consequently resulted in the mitotic cell death. Interestingly, we also observed that AD1 could induce transcription factor ATF6 cleavage and subsequent reduction of the level of ER stress chaperone protein Grp78, and phosphorylated Akt expression. In vivo toxicity studies demonstrated that AD1, with maximum tolerance dose (MTD) of 150 mg/kg, was remarkably less toxic to normal C3H/HeN mice than colchicine (MTD of 1.6 mg/kg). The in vivo efficacy study of AD1 on HCC xenografts are now being investigated in nude mouse model in our laboratories.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4424." @default.
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- W1988833132 date "2010-04-15" @default.
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- W1988833132 title "Abstract 4424: Molecular mechanism study of a novel microtubule-binding agent-induced mitotic cell death of human hepatocellular carcinoma" @default.
- W1988833132 doi "https://doi.org/10.1158/1538-7445.am10-4424" @default.
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