Quercetin Sensitizes Human Leukemic Cells to TRAIL-induced Apoptosis: Involvement of DNA-PK/Akt Signal Transduction Pathway

Quercetin 에 의한 사람백혈병 세포의 TRAIL 에 대한 감수성 증가: DNA-PK/Akt 신호전달경로의 관여

  • Park, Jun-Ik (Department of Biochemistry, Pusan National University School of Medicine) ;
  • Kim, Mi-Ju (Department of Biochemistry, Pusan National University School of Medicine) ;
  • Kim, Hak-Bong (Department of Biochemistry, Pusan National University School of Medicine) ;
  • Bae, Jae-Ho (Department of Biochemistry, Pusan National University School of Medicine) ;
  • Lee, Jea-Won (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) ;
  • 김미주 (부산대학교 의학전문대학원 생화학교실) ;
  • 김학봉 (부산대학교 의학전문대학원 생화학교실) ;
  • 배재호 (부산대학교 의학전문대학원 생화학교실) ;
  • 이재원 (부산대학교 의학전문대학원 생화학교실) ;
  • 박수정 (국립보건원 만성질환연구부) ;
  • 김동완 (창원대학교자연과학대학 미생물학과) ;
  • 강치덕 (부산대학교 의학전문대학원 생화학교실) ;
  • 김선희 (부산대학교 의학전문대학원 생화학교실)
  • Published : 2009.08.30


Despite the fact that many cancer cells are sensitive to TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis, some cancer cells show either partial or complete resistance to TRAIL. Human leukemic K562 and CEM cells also show resistance to TRAIL-induced apoptosis. Novel molecular target and treatment strategies are required to overcome TRAIL resistance of human leukemia cells. Therefore, the purpose of this study was to target key anti-apoptotic molecules deciding TRAIL resistance for sensitization of TRAIL-resistant K562 and CEM cells, and to evaluate the effect of quercetin as a TRAIL sensitizer on these TRAIL-resistant cells. We found that quercetin acted in synergy with TRAIL to enhance TRAIL-induced apoptosis in K562 cells by inhibition of the DNA-PK/Akt signaling pathway, which leads to enhancement of TRAIL-mediated activation of caspases and concurrent cleavage of PARP and up-regulation of Bax. The findings suggest that the DNA-PK/Akt signaling pathway plays an essential role in regulating cells to escape from TRAIL-induced apoptosis, and quercetin could act in synergy with TRAIL to increase apoptosis by inhibition of the DNA-PK/Akt signaling pathway, which overcomes TRAIL-resistance of K562 and CEM cells. This study suggests that DNA-PK might interfere with TRAIL-induced apoptosis in human leukemic cells through activation of the Akt signaling pathway.


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