Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Modulation of Cell Cycle Regulators by Sulforaphane in Human Mepatocarcinoma HepG2 Cells

HepG2 인체간암세포의 세포주기조절인자 발현에 미치는 sulforaphane의 영향

  • Bae, Song-Ja (Department of Food and Nutrition, Silla University and Marine Biotechnology Center for Bio-Functional Material Industries) ;
  • Kim, Gi-Young (Faculty of Applied Marine Science, Cheju National University) ;
  • Yoo, Young-Hyun (Department of Anatomy and Cell Biology, Dong-A University College of Medicine) ;
  • Choi, Byung-Tae (Anatomy and Dongeui University Oriental Medicine and Department of Biomaterial Control(BK21 program), Dongeui University Graduate School) ;
  • Choi, Yung-Hyun (Biochemistry, Dongeui University Oriental Medicine and Department of Biomateriqal Control(BK21 program), Dongeui University Graduate School)
  • 배송자 (신라대학교 자연과학대학 식품영양학과 및 마린바이오산업화지원센터) ;
  • 김기영 (제주대학교 해양과학대학 해양과학부) ;
  • 유영현 (동아대학교 의과대학 해부학교실) ;
  • 최병태 (동의대학교 한의과대학 해부학교실) ;
  • 최영현 (동의대학교 한의과대학 생화학교실 및 대학원 바이오물질제어학과)
  • Published : 2006.12.01
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Abstract

Sulforaphane, an isothiocyanate derived from hydrolysis of glucoraphanin in broccoli and other cruciferous vegetables, was shown to induce phase II detoxification enzymes and inhibit chemically induced mammary tumors in rodents. Recently, sulforaphane is known to induce cell cycle arrest and apoptosis in human canter cells, however its molecular mechanisms are poorly understood. In tile present study, we demonstrated that sulforaphane acted to inhibit proliferation and induce morphological changes of human hepatocarcinoma HepG2 cells. Treatment of HepG2 cells with $10{\mu}M\;or\;15{\mu}M$ sulforaphane resulted in significant G2/M cell cycle arrest as determined by DNA flow cytometry. Moreover, $20{\mu}M$ sulforaphane significantly induced the population of sub-G1 cells suggesting that sulforaphane induced apoptosis. This anti-proliferative effect of sulforaphane was accompanied by a marked inhibition of ryclin A, cyclin 31 and Cdc2 protein. However, the levels of tumor suppressor p53 and Cdk inhibitor p21 mRNA and protein expression were significantly increased by sulforaphane treatment in a concentration-dependent manner. Although further studies are needed, the present work suggests that sulforaphane may be a potential rhemoprevetiveichemotherapeucc agent for the treatment of human cancer cells.

브로콜리를 포함한 십자화과 식물에서 glucoraphanin의 가수분해를 통해 생성되는 isothiocyanate의 일종인 sulforaphane은 역학적 조사를 포함한 다양한 선행 연구에서 강력한 암예방 효과를 가지는 것으로 알려져 있다. 항암효과에 관한 최근 연구 결과에 따르면 sulforaphane은 다양한 인체암세포의 증식을 억제하고 apoptosis를 유발할 수 있는 것으로 알려지고 있으나, 정확한 분자생물학적 기전은 밝혀져 있지 않은 상태이다. 본 연구에서는 sulforaphane의 항암작용 기전을 조사하기 위하여 HepG2 인체간암세포의 증식에 미치는 sulforaphane의 영 향을 조사하였다. Sulforaphane의 처리에 의한 HepG2 세포의 증식억제 및 형태적 변형은 세포주기 G2/M arrest 및 apoptosis 유발과 밀접한 관련이 있음을 알 수 있었다. RT-PCR 및 Western blot 분석 결과, sulforaphane 처리에 의하여 cyclin A 및 cyclin B1, Cdc2의 발현이 단백질 수준에서 선택적으로 저하되었으며, 종양억제 유전자 p53 및 Cdk inhibitor p21의 발현은 전사 및 번역 수준에서 sulforaphane 처리 농도 의존적으로 증가되었다. Sulforaphane의 항암 기전을 규명하기 위해서는 더 많은 연구가 부가적으로 필요하겠지만, 본 연구의 결과들에 의하면 sulforaphane은 강력한 인체암세포의 증식 억제 및 항암작용이 있을 것을 시사하여 준다고 할 수 있다.

Keywords

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