Glenn Rosen

Publication Details

  • Triptolide and chemotherapy cooperate in tumor cell apoptosis - A role for the p53 pathway JOURNAL OF BIOLOGICAL CHEMISTRY Chang, W. T., Kang, J. J., Lee, K. Y., Wei, K., Anderson, E., Gotmare, S., Ross, J. A., Rosen, G. D. 2001; 276 (3): 2221-2227

    Abstract:

    Triptolide (PG490), a diterpene triepoxide, is a potent immunosuppressive agent extracted from the Chinese herb Tripterygium wilfordii. We have previously shown that triptolide blocks NF-kappaB activation and sensitizes tumor necrosis factor (TNF-alpha)-resistant tumor cell lines to TNF-alpha-induced apoptosis. We show here that triptolide enhances chemotherapy-induced apoptosis. In triptolide-treated cells, the expression of p53 increased but the transcriptional function of p53 was inhibited, and we observed a down-regulation of p21(waf1/cip1), a p53-responsive gene. The increase in levels of the p53 protein was mediated by enhanced translation of the p53 protein. Additionally, triptolide induced accumulation of cells in S phase and blocked doxorubicin-mediated accumulation of cells in G(2)/M and doxorubicin-mediated induction of p21. Our data suggest that triptolide, by blocking p21-mediated growth arrest, enhances apoptosis in tumor cells.

    View details for Web of Science ID 000166528000076

    View details for PubMedID 11053449

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