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Quercetin Potentiates TRAIL-induced Apoptosis in Human Colon KM12 Cells

사람 대장암 KMl2세포에서 quercetin 의한 TRAIL이 유도하는 세포사멸의 증가

  • Park, Jun-Ik (Department of Biochemistry, Pusan National University School of Medicine) ;
  • Kim, Hak-Bong (Department of Biochemistry, Pusan National University School of Medicine) ;
  • Kim, Mi-Ju (Department of Biochemistry, Pusan National University School of Medicine) ;
  • Lee, Jae-Won (Department of Biochemistry, Pusan National University School of Medicine) ;
  • Bae, Jae-Ho (Department of Biochemistry, Pusan National University School of Medicine) ;
  • Park, Soo-Jung (Division of Intractable Diseases, Center for Biomedical Sciences, National Institute of Health) ;
  • Kim, Dong-Wan (Department of Microbiology, College of Natural Sciences, Chang Won National University) ;
  • Kang, Chi-Dug (Department of Biochemistry, Pusan National University School of Medicine) ;
  • Kim, Sun-Hee (Department of Biochemistry, Pusan National University School of Medicine)
  • 박준익 (부산대학교 의학전문대학원 생화학교실) ;
  • 김학봉 (부산대학교 의학전문대학원 생화학교실) ;
  • 김미주 (부산대학교 의학전문대학원 생화학교실) ;
  • 이재원 (부산대학교 의학전문대학원 생화학교실) ;
  • 배재호 (부산대학교 의학전문대학원 생화학교실) ;
  • 박수정 (국립보건원 만성질환연구부) ;
  • 김동완 (창원대학교 자연과학대 미생물학과) ;
  • 강치덕 (부산대학교 의학전문대학원 생화학교실) ;
  • 김선희 (부산대학교 의학전문대학원 생화학교실)
  • Published : 2009.09.30

Abstract

Many cancer cells are sensitive to the TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. However, some cancer cells show either partial or complete resistance to TRAIL. Human colon carcinoma KM12 cells have been shown to be insensitive to TRAIL-induced apoptosis. To overcome TRAIL resistance in KM12 cells, we targeted key anti-apoptotic molecules involved in the modulation of TRAIL resistance in the cells, and evaluated the effects of quercetin as a TRAIL sensitizer in the cells. We found that quercetin acted in synergy with TRAIL to enhance TRAIL-induced apoptosis in KM12 cells by the down-regulation of c-FLIP and DNA-PKcs/Akt and up-regulation of death receptors (DR4/DR5), which led to the enhancement of TRAIL-mediated activation of caspases and subsequent cleavage of PARP, as well as up-regulation of Bax. These findings suggest that the DNA-PKcs/Akt signaling pathway, as well as c-FLIP, play essential roles in regulating cells in the escape from TRAIL-induced apoptosis. Based on these results, this study provides a potential application of quercetin in combination with TRAIL in the treatment of human colon cancer.

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