Mechanism of triptolide-induced apoptosis: effect on caspase activation and Bid cleavage and essentiality of the hydroxyl group of triptolide
| Autor: | Gang Shen, Yusen Liu, Leif D. Nelin, Ranyia Matta, Dehua Pei, Xianxi Wang |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Programmed cell death
Apoptosis Cleavage (embryo) Biochemistry HeLa Structure-Activity Relationship chemistry.chemical_compound Enzyme activator Drug Discovery Tumor Cells Cultured Genetics Humans Fragmentation (cell biology) Antineoplastic Agents Alkylating Molecular Biology Polymerase Genetics (clinical) Caspase biology Chemistry Cell growth Anti-Inflammatory Agents Non-Steroidal Carcinoma Phenanthrenes Triptolide biology.organism_classification Molecular medicine Enzyme Activation Pancreatic Neoplasms Proto-Oncogene Proteins c-bcl-2 Caspases Cancer research biology.protein Epoxy Compounds Molecular Medicine Tripterygium wilfordii Diterpenes BH3 Interacting Domain Death Agonist Protein HeLa Cells Biotechnology |
| Zdroj: | Journal of Molecular Medicine. 84:405-415 |
| ISSN: | 1432-1440 0946-2716 |
| DOI: | 10.1007/s00109-005-0022-4 |
| Popis: | Triptolide is a compound extracted from the Chinese herb Tripterygium wilfordii Hook. f. Triptolide has potent anticancer activity. However, the mechanisms by which triptolide exerts its anticancer activities remain unclear. To explore the molecular mechanisms involved in the anticancer activity of triptolide, we have examined the effect of triptolide on the growth of pancreatic carcinoma PANC-1 and cervical adenocarcinoma HeLa cells. We found that treatment of both HeLa and PANC-1 cells with triptolide potently suppressed cell growth and induced apoptosis, indicated by nuclear fragmentation and blebbing. In both HeLa and PANC-1 cells, apoptosis induced by triptolide was associated with activation of both caspase-3 and caspase-8, and cleavage of poly(ADP-ribose) polymerase and Bid. Moreover, in HeLa cells, caspase-9 is also significantly activated in response to triptolide. Overexpression of Bcl-2 in HeLa cells substantially attenuated triptolide-induced apoptosis. Interestingly, substitution of the 14-OH of triptolide with an acetyl group abrogated both its anticancer and its antiinflammatory activities. Our studies suggest that triptolide may exert its anticancer effects by initiating apoptosis through both death-receptor- and mitochondria-mediated pathways. Our results indicate that both the apoptosis-promoting and the antiinflammatory activities of triptolide depend on the 14-OH group. |
| Databáze: | OpenAIRE |
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