Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Induction of G2/M Arrest of the Cell Cycle by Genistein in Human Bladder Carcinoma and Leukemic Cells

인체 방광암 및 백혈병세포에서 genistein에 의한 세포주기 G2/M arrest 유발에 관한 연구

  • Kim, Eu-Kyum (Korea Science Academy) ;
  • Myong, You-Ho (Korea Science Academy) ;
  • Song, Kwan-Sung (Korea Science Academy) ;
  • Lee, Ki-Hong (Korea Science Academy) ;
  • Rhu, Chung-Ho (Division of Applied Life Science, Gyeongsang National University) ;
  • Choi, Yung-Hyun (Department of Biochemistry, Dongeui University College of Oriental Medicine and Department of Biomaterial Control, Dongeui University Graduate School)
  • 김의겸 (한국과학영재학교) ;
  • 명유호 (한국과학영재학교) ;
  • 송관성 (한국과학영재학교) ;
  • 이기홍 (한국과학영재학교) ;
  • 류충호 (경상대학교 농과대학 식품공학과) ;
  • 최영현 (동의대학교 한의과대학 생화학교실 및 대학원 바이오물질제어학과)
  • Published : 2006.07.31
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Abstract

Genistein, a natural isoflavonoid phytoestrogen, is a strong inhibitor of protein tyrosine kinase and DNA topoisomerase activities. There are several studies documenting molecular alterations leading to cell cycle arrest and induction of apoptosis by genistein as a chemopreventive agent in a variety of cancer cell lines; however, its mechanism of action and its molecular targets on human bladder carcinoma and leukemic cells remain unclear. In the present study, we have addressed the mechanism of action by which genistein suppressed the proliferation of T24 bladder carcinoma and U937 leukemic cells. Genistein significantly inhibited the cell growth and induced morphological changes, and induced the G2/M arrest of the cell cycle in both T24 and U937 cells with a relatively stronger cytotoxicity in U937. The G2/M arrest in T24 cells was associated with the inhibition of cyclin A, cyclin B1 and Cdc25C protein expression without alteration of tumor suppressor p53 and cyclin-dependent kinase (Cdk) inhibitor p21(WAF1/CIP1). However, the inhibitory effects of genistein on the cell growth of U937 cells were connected with a marked inhibition of cyclin B1 and an induction of Cdk inhibitor p21 proteins by p53-independent manner. These data suggest that genistein may exert a strong anticancer effect and additional studies will be needed to evaluate the different mechanisms between T24 and U937 cells.

본 연구에서는 T24 인체방광암 및 U937 백혈병 세포의 증식에 미치는 genistein의 영향을 조사 하였다. Genistein이 처리된 T24 및 U937 세포는 처리 농도 의존적으로 세포의 증식이 현저히 감소되었으며 심한 형태적 변형이 동반되었으나, U937 세포에서 보다 높은 감수성을 보였다. 이러한 T24 및 U937 세포의 증식억제 및 형태 변형은 G2/M기의 세포주기 억제 및 apoptosis 유발과 연관성이 있음을 flow cytometry를 이용한 세포주기의 분석을 통하여 확인하였다. T24 세포에서 genistein에 의한 G2/M arrest는 cyclin A, cyclin B1 및 Cdc25C 등의 단백질 발현 감소와 연관성이 있었으나, 종양억제 유전자 p53 및 Cdk inhibitor p21의 발현에는 큰 변화가 없었다. U937 세포에서 genistein에 의한 G2/M arrest는 cyclin B1 및 p53 비의존적인 p21의 발현 증가와 연관성이 있었다. 이상의 결과들은 현재까지 거의 연구가 진행된 바 없는 인체방광암 및 백혈병 세포에서 genistein의 항암작용을 이해하는데 중요한 자료가 될 것이고 나아가 genistein을 포함한 그와 유사한 항암제 후보물질들의 연구에 있어서 기초 자료로서 사용될 수 있을 것으로 생각된다.

Keywords

References

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