Apoptosis

, Volume 12, Issue 2, pp 423–431 | Cite as

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

  • 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
Report

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.

Keywords

Exisulind α-Tocopheryl succinate Apoptosis Caspase JNK Colon cancer 

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Copyright information

© Springer Science + Business Media, LLC 2006

Authors and Affiliations

  • Soo-Jeong Lim
    • 1
  • Young-Ju Lee
    • 2
  • Dae-Hun Park
    • 2
  • Eunmyong Lee
    • 1
  • Moon-Kyung Choi
    • 2
  • Wanseo Park
    • 2
  • Kyung-Hee Chun
    • 2
  • Han-Gon Choi
    • 3
  • Jung Sik Cho
    • 4
  1. 1.Department of Bioscience and BiotechnologySejong UniversityKorea
  2. 2.Research InstituteNational Cancer CenterGoyangKorea
  3. 3.College of PharmacyYeungnam UniversityGyongsanKorea
  4. 4.National Institute of Toxicological ResearchSeoulKorea

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