Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Induction of G1 Arrest by Methanol Extract of Lycopus lucidus in Human Lung Adenocarcinoma A549 Cells

택란 메탄올 추출물에 의한 인체 폐암 세포주 A549의 G1 arrest 유발

  • Park, Hyun-Jin (Blue-Bio Industry RIC, Dong-Eui University) ;
  • Jin, Soojung (Blue-Bio Industry RIC, Dong-Eui University) ;
  • Oh, You Na (Blue-Bio Industry RIC, Dong-Eui University) ;
  • Yun, Seung-Geun (Department of Life Science and Biotechnology, College of Natural Sciences, Dong-Eui University) ;
  • Lee, Ji-Young (Blue-Bio Industry RIC, Dong-Eui University) ;
  • Kwon, Hyun Ju (Blue-Bio Industry RIC, Dong-Eui University) ;
  • Kim, Byung Woo (Blue-Bio Industry RIC, Dong-Eui University)
  • 박현진 (동의대학교 블루바이오 소재개발 센터) ;
  • 진수정 (동의대학교 블루바이오 소재개발 센터) ;
  • 오유나 (동의대학교 블루바이오 소재개발 센터) ;
  • 윤승근 (동의대학교 자연과학대학 생명응용학과) ;
  • 이지영 (동의대학교 블루바이오 소재개발 센터) ;
  • 권현주 (동의대학교 블루바이오 소재개발 센터) ;
  • 김병우 (동의대학교 블루바이오 소재개발 센터)
  • Received : 2013.07.10
  • Accepted : 2013.09.17
  • Published : 2013.09.30
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Abstract

Induction of G1 Arrest by Methanol Extract of Lycopus lucidus in Human Lung Adenocarcinoma A549 Cells Lycopus lucidus, a herbaceous perennial, is used as a traditional remedy in East Asia, including China and Korea. It has been reported that L. lucidus has anti-allergic effects, inhibitory effects on cholesterol acyltransferase in high glucose-induced vascular inflammation, and anti-proliferative effects in human breast cancer cells. However, the molecular mechanisms of the anti-cancer effects of L. lucidus have not yet been fully determined. In this study, we evaluated the anti-cancer effect and the mechanism of action of L. lucidus in human lung adenocarcinoma A549 cells using methanol extracts of L. lucidus (MELL). MELL treatment showed cytotoxic activity in a dose-dependent manner and induced G1 arrest in A549 cells. The induction of G1 arrest by MELL was associated with the up-regulation of phospho-CHK2 and the down-regulation of Cdc25A phosphatase. In addition, MELL treatment induced decreased expression of G1/S transition-related proteins, including CDK2, CDK4, CDK6, cyclin D1 and cyclin E. MELL also regulated the mRNA expression of CDK2 and cyclin E. On the other hand, the expression of p53 and the cyclin-dependent kinase inhibitor p21 was not induced by MELL. Collectively, these results suggest that MELL may exert an anti-cancer effect by cell cycle arrest at G1 phase through the ATM/CHK2/Cdc25A/CDK2 pathway in A549 cells.

본 연구에서는 인체 폐암 세포인 A549를 사용하여 택란 메탄올 추출물의 항암활성과 그 분자적 기전에 관하여 연구하였다. 먼저 택란 추출물이 A549의 세포증식에 미치는 영향을 알아본 결과 처리 농도 및 시간 의존적으로 A549의 성장이 저해되었으며, 세포 주기 변화를 분석한 결과 강력한 G1 arrest가 유도되는 것을 확인하였다. 이러한 택란 추출물에 의한 G1 arrest는 세포주기 조절 단백질인 Cyclin D1, Cyclin E 및 Cyclin-dependent kinase인 CDK2, CDK4, CDK6의 발현 감소와 연관되어 있었다. 또한 택란 추출물에 의한 CDK/Cyclin complex의 발현 저해는 DNA 손상에 의해 활성화되는 CHK2의 활성화 형태인 p-CHK2의 발현 증가에 따른 CDK 활성화 효소인 Cdc25A phosphatase의 발현 억제에 의해 나타나는 결과로 사료된다. 반면 종양억제유전자인 p53 및 CDK 억제제인 p21과 p27의 발현량은 증가되지 않았다. 이러한 결과들로부터 택란 추출물은 DNA damage에 의한 ATM/CHK2/Cdc25A/CDK2 pathway를 통해 A549의 G1 arrest를 유도하여 세포의 증식을 억제할 것으로 판단되며, 이때 택란 추출물에 의해 유도되는 G1 arrest는 p53 비의존적인 경로일 것으로 사료된다. 본 연구결과는 택란이 Cdc25A를 target으로 하는 새로운 항암활성 소재로서 사용될 수 있는 가능성을 시사한다. 또한 본 연구결과는 택란 추출물의 세포주기 조절에 의한 항암기전을 이해하고 향후 지속적 연구를 하는 데 있어서 귀중한 기초자료로 사용될 수 있을 것이다.

Keywords

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