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Water Extract of Allium sativum L. Induces Apoptosis in Human Leukemia U937 Cells through Reactive Oxygen Species Generation

마늘 열수 추출물의 활성산소종 생성을 통한 인체백혈병세포의 apoptosis 유발

  • Choi, Woo-Young (Department of Biochemistry, Dongeui University) ;
  • Chung, Kyung-Tae (Department of Laboratory Science Dongeui University) ;
  • Yoon, Tae-Kyung (Department of Environmental Engineering Major Dongeui University) ;
  • Choi, Byung-Tae (Department of Anatomy, Graduate School of Oriental Medicine, Pusan National University) ;
  • Lee, Yong-Tae (Department of Physiology, College of Oriental Medicine Dongeui University) ;
  • Lee, Won-Ho (Department of Biology, College of Natural Sciences, Pusan National University) ;
  • Ryu, Chung-Ho (Division of Applied Life Science, Institute of Agriculture and Life Science, Gyeongsang National University) ;
  • Choi, Yung-Hyun (Department of Biochemistry, Dongeui University)
  • 최우영 (동의대학교 한의과대학 생화학교실) ;
  • 정경태 (동의대학교 자연과학대학 임상병리학과) ;
  • 윤태경 (동의대학교 공과대학 환경공학과) ;
  • 최병태 (부산대학교 한의학전문대학원 해부학교실) ;
  • 이용태 (동의대학교 한의과대학 생리학교실) ;
  • 이원호 (부산대학교 자연과학대학 생물학과) ;
  • 류충호 (경상대학교 농업생명과학대학 응용생명공학과) ;
  • 최영현 (동의대학교 한의과대학 생화학교실)
  • Published : 2007.12.30

Abstract

The health benefits of garlic (Allium sativum L.) are derived from a wide variety of components and from the different ways it is administered. The known health benefits of garlic include cardiovascular protective effects, stimulation of immune function, reduction of blood glucose level, protection against microbial, viral and fungal infections, as well as anticancer effects. In the present study, it was examined the effects of water extract of A. sativum (WEAS) on the growth of cultured human tumor cells in order to investigate its anti-proliferative mechanism. Treatment of WEAS to tumor cells resulted in the growth inhibition, especially in leukemia cells, which was associated with induction of G2/M arrest of the cell cycle and apoptosis. In order to further explore the critical events leading to apoptosis in WEAS-treated U937 human leukemia cells, the following effects of WEAS on components of the mitochondrial apoptotic pathway were examined: generation of reactive oxygen species (ROS), alteration of the mitochondrial membrane potential (MMP), and the expression changes of Bcl-2 and IAP family proteins. The cytotoxic effect of WEAS was mediated by its induction of apoptosis as characterized by the occurrence of DNA ladders, apoptotic bodies and chromosome condensation in U937 cells. The WEAS-induced apoptosis in U937 cells was correlated with the generation of intracellular ROS, collapse of MMP, activation of caspase-3 and down-regulation of anti-apoptotic proteins. The quenching of ROS generation with antioxidant N-acetyl-L-cysteine conferred significant protection against WEAS-elicited ROS generation, caspase-3 activation, G2/M arrest and apoptosis. In conclusion, the present study reveals that the cellular ROS generation plays a pivotal role in the initiation of WEAS-triggered apoptotic death in U937 cells.

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