Triptolide and chemotherapy cooperate in tumor cell apoptosis. A role for the p53 pathway.

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.
Authors	W T Chang, J J Kang, K Y Lee, K Wei, E Anderson, S Gotmare, J A Ross, G D Rosen
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 276 Issue 3 Pg. 2221-7 (Jan 19 2001) ISSN: 0021-9258 [Print] United States
PMID	11053449 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antineoplastic Agents DNA Primers DNA, Neoplasm Diterpenes Epoxy Compounds Phenanthrenes Tumor Suppressor Protein p53 triptolide Doxorubicin Oncogene Protein p21(ras)
Topics	Animals Antineoplastic Agents (pharmacology) Apoptosis (drug effects, physiology) Base Sequence Cell Cycle (drug effects) DNA Primers DNA, Neoplasm (metabolism) Diterpenes (pharmacology) Doxorubicin (pharmacology) Drug Synergism Epoxy Compounds Humans Mice Neoplasms (pathology) Oncogene Protein p21(ras) (antagonists & inhibitors, metabolism) Phenanthrenes Protein Binding Tumor Cells, Cultured Tumor Suppressor Protein p53 (physiology)

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