Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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G1 Arrest of the Cell Cycle by Gomisin N, a Dibenzocyclooctadiene Lignan, Isolated from Schizandra chinensis Baill in Human Leukemia U937 Cells

오미자에서 분리된 dibenzocyclooctadiene lignan의 일종인 gomisin N에 의한 인체혈구암세포의 세포주기 G1 arrest 유발

  • Park, Cheol (Blue-Bio Industry Regional Innovation Center, Dongeui University) ;
  • Hwang, Hye-Jin (Department of Food and Nutrition, College of Human Ecology, Dongeui University) ;
  • Choi, Byung-Tae (Division of Meridian and Structural Medicine, School of Korean Medicine, Pusan National University) ;
  • Choi, Tae-Hyun (Department of Ophthalmic Optics, Daegu Technical University) ;
  • Kim, Byung-Woo (Department of Life Science and Biotechnology, College of Natural Sciences, Dongeui University) ;
  • Choi, Young-Whan (Department of Horticultural Bioscience, Pusan National University) ;
  • Choi, Yung-Hyun (Department of Biomaterial Control, Graduate School, Dongeui University)
  • 박철 (동의대학교 블루바이오소재개발센터) ;
  • 황혜진 (동의대학교 생활과학대학 식품영양학과) ;
  • 최병태 (부산대학교 한의학전문대학원 경락구조의학부) ;
  • 최태현 (대구공업대학 안경광학과) ;
  • 김병우 (동의대학교 자연과학대학 응용생물학과) ;
  • 최영환 (부산대학교 생명자원과학대학 원예학과) ;
  • 최영현 (동의대학교 대학원 바이오물질제어학과)
  • Received : 2010.03.23
  • Accepted : 2010.07.15
  • Published : 2010.07.30
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Abstract

We investigated the anti-cancer effects of two dibenzocyclooctadiene lignans, gomisin A and gomisin N, isolated from Schizandra chinensis Baill, in human promyelocytic U937 cells. Gomisin N, but not gomisin A, inhibited cell growth in a concentration-dependent manner, which was associated with the induction of G1 arrest of the cell cycle. G1 arrest induced by gomisin N was correlated with down-regulation of cyclin E, cyclin-dependent kinase (Cdk) 2 and Cdk4, and a concomitant up-regulation of Cdk inhibitors such as p16 (INK4A) and p21 (WAF1/CIP1). Furthermore, gomisin N inhibited phosphorylation of retinoblastoma protein (pRB) and p130, and expression of transcription factor E2Fs. The results indicated that growth inhibition by gomisin N is related to cell cycle arrest at G1 in U937 cells and these findings suggest that gomisin N may be a useful chemotherapeutic agent.

본 연구에서는 오미자에서 분리된 dibenzocyclooctadiene lignan의 일종인 gomisin A와 gomisin N에 대한 항암효능을 U937 인체혈구암세포를 대상으로 조사하였다. Gomisin N은 처리농도의 증가에 따라 U937 세포의 증식을 억제하였으나 동일조건에서 gomisin A는 세포독성 효과를 나타내지 못하였으며, gomisin N에 의한 U937 세포의 증식억제는 세포주기 G1 arrest 유발에 의한 것이었다. Gomisin N에 의한 G1 arrest는 cyclin E, cyclin-dependent kinase (Cdk) 2 및 Cdk4의 발현 억제와 Cdk inhibitor인 p16 (INK4A) 및 p21 (WAF1/CIP1)의 발현 증가와 연관성이 있었으나, gomisin A는 세포주기 인자들의 발현에 유의적인 변화를 유발하지 않았다. 또한 gomisin N은 retinoblastoma 단백질군인 pRB 및 p130의 인산화를 억제하였으며, 전사조절인자인 E2F 단백질들의 발현을 억제하였다. 본 연구의 결과에서 gomisin N에 의한 U937 세포의 증식억제는 세포주기 조절인자들의 발현 변화를 통한 G1 arrest 유발에 의한 것임을 알 수 있었으며, gomisin N은 암예방 및 항암활성 후보불질로서의 개발 가능성이 있음을 알 수 있었다.

Keywords

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