| Triptolide inactivates Akt and induces caspase-dependent death in cervical cancer cells via the mitochondrial pathway. | |
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MedLine Citation:
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PMID: 20878065 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Triptolide, the main active component of the traditional Chinese herbal medicine Tripterygium wilfordii Hook F, has been shown to have potent immunosuppressive and anti-inflammatory properties. Here, we investigated the pro-apoptotic effect of triptolide in human cervical cancer cells and its underlying mechanisms. Exposure of cervical cancer cells to triptolide induced apoptosis, which was accompanied by loss of mitochondrial membrane potential, caspase processing (caspase-8, -9 and -3), and cleavage of the caspase substrate, poly(ADP-ribose) polymerase. The cytotoxic effects of triptolide were significantly inhibited by the caspase inhibitor, z-VAD-fmk. Triptolide-induced apoptosis was associated with a marked reduction in Akt phosphorylation and was exacerbated by LY294002 (phosphatidylinositol-3'-kinase inhibitor). Conversely, it was attenuated by Akt overexpression. Triptolide-induced apoptosis was also associated with downregulation of Mcl-1 and was significantly inhibited by Mcl-1 overexpression. These findings show that triptolide induces caspase-dependent, mitochondria-mediated apoptosis in cervical cancer cells, in part, by negatively regulating Akt and Mcl-1. |
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Authors:
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Min Jung Kim; Tae Hwa Lee; Sung Han Kim; Yeon-Joo Choi; Jeonghoon Heo; Young-Ho Kim |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: International journal of oncology Volume: 37 ISSN: 1791-2423 ISO Abbreviation: Int. J. Oncol. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-09-29 Completed Date: 2011-01-25 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9306042 Medline TA: Int J Oncol Country: Greece |
Other Details:
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Languages: eng Pagination: 1177-85 Citation Subset: IM |
Affiliation:
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Shinsegae Women's Hospital, Busan, Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents, Alkylating
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pharmacology* Apoptosis / drug effects* Blotting, Western Caspases / drug effects, metabolism Cell Line, Tumor Cell Separation DNA Fragmentation Diterpenes / pharmacology* Epoxy Compounds / pharmacology Female Flow Cytometry Hela Cells Humans Membrane Potential, Mitochondrial / drug effects Mitochondria / drug effects* Phenanthrenes / pharmacology* Proto-Oncogene Proteins c-akt / drug effects Proto-Oncogene Proteins c-bcl-2 / drug effects Reverse Transcriptase Polymerase Chain Reaction Transfection Uterine Cervical Neoplasms / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents, Alkylating; 0/Diterpenes; 0/Epoxy Compounds; 0/Phenanthrenes; 0/Proto-Oncogene Proteins c-bcl-2; 0/myeloid cell leukemia sequence 1 protein; 38748-32-2/triptolide; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 3.4.22.-/Caspases |
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