Alpha-tocopheryl succinate sensitizes human colon cancer cells to exisulind-induced apoptosis
- Authors
- Lim, Soo-Jeong; Lee, Young-Ju; Park, Dae-Hun; Lee, Eunmyong; Choi, Moon-Kyung; Park, Wanseo; Chun, Kyung-Hee; Choi, Han-Gon; Cho, Jung Sik
- Issue Date
- Feb-2007
- Publisher
- SPRINGER
- Keywords
- exisulind; alpha-tocopheryl succinate; apoptosis; caspase; JNK; colon cancer
- Citation
- APOPTOSIS, v.12, no.2, pp.423 - 431
- Indexed
- SCIE
SCOPUS
- Journal Title
- APOPTOSIS
- Volume
- 12
- Number
- 2
- Start Page
- 423
- End Page
- 431
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/43898
- DOI
- 10.1007/s10495-006-0620-9
- ISSN
- 1360-8185
- 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.
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