| Alpha-tocopheryl succinate potentiates the paclitaxel-induced apoptosis through enforced caspase 8 activation in human H460 lung cancer cells. | |
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MedLine Citation:
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PMID: 19561399 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Paclitaxel is one of the chemotherapeutic drugs widely used for the treatment of nonsmall cell lung cancer (NSCLC) patients. Here, we tested the ability of alpha-tocopheryl succinate (TOS), another promising anticancer agent, to enhance the paclitaxel response in NSCLC cells. We found that sub-apoptotic doses of TOS greatly enhanced paclitaxel-induced growth suppression and apoptosis in the human H460 NSCLC cell lines. Our data revealed that this was accounted for primarily by an augmented cleavage of poly(ADP-ribose) polymerase (PARP) and enhanced activation of caspase-8. Pretreatment with z-VAD-FMK (a pan-caspase inhibitor) or z-IETD-FMK (a caspase-8 inhibitor) blocked TOS/paclitaxel cotreatment-induced PARP cleavage and apoptosis, suggesting that TOS potentiates the paclitaxel-induced apoptosis through enforced caspase 8 activation in H460 cells. Furthermore, the growth suppression effect of TOS/paclitaxel combination on human H460, A549 and H358 NSCLC cell lines were synergistic. Our observations indicate that combination of paclitaxel and TOS may offer a novel therapeutic strategy for improving paclitaxel drug efficacy in NSCLC patient therapy as well as for potentially lowering the toxic side effects of paclitaxel through reduced drug dosage. |
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Authors:
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Soo-Jeong Lim; Moon Kyung Choi; Min Jung Kim; Joo Kyoung 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: Experimental & molecular medicine Volume: 41 ISSN: 1226-3613 ISO Abbreviation: Exp. Mol. Med. Publication Date: 2009 Oct |
Date Detail:
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Created Date: 2009-10-30 Completed Date: 2010-06-10 Revised Date: 2010-09-27 |
Medline Journal Info:
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Nlm Unique ID: 9607880 Medline TA: Exp Mol Med Country: Korea (South) |
Other Details:
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Languages: eng Pagination: 737-45 Citation Subset: IM |
Affiliation:
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Department of Bioscience and Biotechnology, Sejong University, Seoul 143-747, Korea. sjlim@sejong.ac.kr |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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pharmacology* Apoptosis / drug effects* Carcinoma, Non-Small-Cell Lung / drug therapy*, metabolism, pathology Caspase 8 / metabolism Cell Growth Processes / drug effects Cell Line, Tumor Drug Synergism Drug Therapy, Combination Humans Neoplastic Stem Cells Paclitaxel / pharmacology alpha-Tocopherol / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 33069-62-4/Paclitaxel; 59-02-9/alpha-Tocopherol; EC 3.4.22.-/Caspase 8 |
| Comments/Corrections | |
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