| Alpha-tocopheryl succinate sensitizes human colon cancer cells to exisulind-induced apoptosis. | |
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MedLine Citation:
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PMID: 17191116 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Sulindac sulfone (also known as exisulind) and its chemical derivatives are promising anticancer agents capable of inducing apoptosis in a variety of malignant cell types with minimal toxicity to normal cells. Here, we tested the ability of alpha-tocopheryl succinate (TOS), another promising anticancer agent, to sensitize colon cancer cells to exisulind-induced apoptosis. We found that sub-apoptotic doses of TOS greatly enhanced exisulind-induced growth suppression and apoptosis in the HCT116, LoVo and SNU-C4 human colon cancer cell lines. Our results revealed that this was accounted for primarily by an augmented cleavage of poly(ADP-ribose) polymerase (PARP) and enhanced activation of caspase-8, -9 and -3. Pretreatment with z-VAD-FMK (a pan-caspase inhibitor), z-IETD-FMK (a caspase-8 inhibitor) or z-LEHD-FMK (a caspase-9 inhibitor) blocked TOS and exisulind cotreatment-induced PARP cleavage and apoptosis. Furthermore, TOS/exisulind cotreatment induced JNK phosphorylation, while pretreatment with SP600151 (a JNK inhibitor) partially blocked cotreatment-induced caspase-dependent PARP cleavage and apoptosis. Taken together, these findings indicate that TOS sensitizes human colon cancer cells to exisulind-induced apoptosis. Apoptotic synergy induced by exisulind plus TOS seems likely to be mediated through a mechanism involving activation of caspases and JNK. |
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Authors:
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Soo-Jeong Lim; Young-Ju Lee; Dae-Hun Park; Eunmyong Lee; Moon-Kyung Choi; Wanseo Park; Kyung-Hee Chun; Han-Gon Choi; Jung Sik Cho |
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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: Apoptosis : an international journal on programmed cell death Volume: 12 ISSN: 1360-8185 ISO Abbreviation: Apoptosis Publication Date: 2007 Feb |
Date Detail:
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Created Date: 2007-01-25 Completed Date: 2007-06-07 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 9712129 Medline TA: Apoptosis Country: United States |
Other Details:
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Languages: eng Pagination: 423-31 Citation Subset: IM |
Affiliation:
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Department of Bioscience and Biotechnology, Sejong University, Seoul, 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* Caspases / antagonists & inhibitors Cell Growth Processes / drug effects Colonic Neoplasms / pathology* Drug Synergism Enzyme Activation / drug effects Enzyme Inhibitors / pharmacology HCT116 Cells Humans JNK Mitogen-Activated Protein Kinases / metabolism Sulindac / analogs & derivatives*, pharmacology Tocopherols Vitamin E / analogs & derivatives*, pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Enzyme Inhibitors; 1406-18-4/Vitamin E; 1406-66-2/Tocopherols; 38194-50-2/Sulindac; 59864-04-9/sulindac sulfone; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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