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Alpha-tocopheryl succinate sensitizes human colon cancer cells to exisulind-induced apoptosis

Title
Alpha-tocopheryl succinate sensitizes human colon cancer cells to exisulind-induced apoptosis
Author
최한곤
Keywords
exisulind; alpha-tocopheryl succinate; apoptosis; caspase; JNK; colon cancer
Issue Date
2007-02
Publisher
SPRINGER
Citation
APOPTOSIS, v. 12, No. 2, Page. 423-431
Abstract
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.
URI
https://link.springer.com/article/10.1007/s10495-006-0620-9http://repository.hanyang.ac.kr/handle/20.500.11754/106261
ISSN
1360-8185
DOI
10.1007/s10495-006-0620-9
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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