Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Induction of Mitotic Arrest and Apoptosis by Diallyl Trisulfide in U937 Human Leukemia Cells

U937 인체혈구암세포에서 diallyl trisulfide에 의한 mitotic arrest와 apoptosis 유발

  • Park, Hyun Soo (School of Korean Medicine, Busan National University) ;
  • Lee, Jun Hyuk (Biotechnology Examination Division, Chemistry and Biotechnology Examination Bureau, Korean Intellectual Property Office) ;
  • Son, Byoung Yil (Blue-Bio Industry Regional Innovation Center & Dongeui University) ;
  • Choi, Byung Tae (School of Korean Medicine, Busan National University) ;
  • Choi, Yung Hyun (Anti-Aging Research Center & Dongeui University)
  • 박현수 (부산대학교 한의학전문대학원) ;
  • 이준혁 (특허청 화학생명공학심사국 생명공학심사과) ;
  • 손병일 (동의대학교 Blue-Bio 소재 개발 및 실용화 지원 센터) ;
  • 최병태 (부산대학교 한의학전문대학원) ;
  • 최영현 (동의대학교 항노화연구소)
  • Received : 2013.03.07
  • Accepted : 2013.03.22
  • Published : 2013.05.30
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Abstract

Diallyl trisulfide (DATS), one of the major organosulfur components of garlic (Allium sativum), has various biological effects such as anti-microbial and anti-cancer activities. However, the molecular mechanisms of growth inhibition related to cell cycle arrest are poorly understood. In this study, we investigated the effects of DATS on cell cycle progression in U937 human leukemia cells. Treatment with DATS in U937 cells resulted in inhibition of cell viability through G2/M arrest and apoptosis. DATS-induced G2/M arrest was associated with up-regulation of cyclin B1 and cyclin-dependent kinase 1 (CDK1). DATS also significantly increased levels of phospho-histone H3, which is a mitosis-specific marker, indicating that DATS induced mitotic arrest but not G2 arrest in U937 cells. DATS treatment also generated the reactive oxygen species (ROS) in U937 cells; however, pretreatment with N-acetyl-l-cysteine (NAC), a ROS scavenger, significantly attenuated DATS-induced mitotic arrest and apoptosis. Taken together, our data indicate that DATS exhibits anti-cancer effects through mitotic arrest and apoptosis in a ROS-dependent manner.

본 연구에서는 마늘에서 유래된 생리활성 물질인 diallyl trisulfide (DATS) 처리에 따른 U937 인체혈구암세포의 증식억제가 apoptosis 및 cell cycle arrest 유발과 관련이 있는지 조사하였다. U937 세포증식은 DATS에 의해 농도 및 시간 의존적으로 감소함을 확인 하였고, 이는 apoptosis에 의한 직접적인 세포죽음과 CDK1 및 cyclin B1의 발현 증가 및 histone H3의 인산화와 연관된 mitotic arrest와 관련이 있음을 알 수 있었다. 또한 DATS 처리 초기에 reactive oxygen species (ROS)의 생성이 매우 증가되었으나, ROS scavenger (N-acetyl-l-cysteine)에 의한 인위적 ROS 생성의 억제는 DATS에 의한 apoptosis 및 mitotic arrest를 완벽하게 차단시켰다. 이는 U937 세포에서 DATS에 의해 유도된 apoptosis 및 mitotic arrest가 ROS에 의해 매개된다는 것을 의미하며, 본 연구의 결과는 DATS가 인체혈구암세포에서 세포증식억제와 관련된 항암기전을 이해할 수 있는 기초자료로서 매우 유용하게 사용될 것이라 생각된다.

Keywords

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