Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Silibinin Inhibits Cell Growth and Induces Apoptosis through Cell-cycle Arrest in PC-3 Prostate Cancer Cells

인간 전립선 암세포 PC-3 세포에서 Silibinin의 세포주기조절을 통한 세포사멸 유도 효과

  • Kim, Sang-Hun (Department of Microbiology and Immunology, Pusan National University School of Medicine) ;
  • Kim, Kwang-Youn (Department of Microbiology and Immunology, Pusan National University School of Medicine) ;
  • Yu, Sun-Nyoung (Department of Microbiology and Immunology, Pusan National University School of Medicine) ;
  • Jeon, Hyun-Joo (Department of Microbiology and Immunology, Pusan National University School of Medicine) ;
  • Jin, Young-Rang (Medical Research Institute, Pusan National University) ;
  • Lee, Chang-Min (Department of Internal Medicine, Yale University School of Medicine) ;
  • Ahn, Soon-Cheol (Department of Microbiology and Immunology, Pusan National University School of Medicine)
  • 김상헌 (부산대학교 의학전문대학원 미생물학 및 면역학 교실) ;
  • 김광연 (부산대학교 의학전문대학원 미생물학 및 면역학 교실) ;
  • 유선녕 (부산대학교 의학전문대학원 미생물학 및 면역학 교실) ;
  • 진영랑 (부산대학교 의학전문대학원 미생물학 및 면역학 교실) ;
  • 전현주 (부산대학교 의학연구소) ;
  • 이창민 (예일대학교 호흡기내과) ;
  • 안순철 (부산대학교 의학전문대학원 미생물학 및 면역학 교실)
  • Received : 2011.09.02
  • Accepted : 2011.11.11
  • Published : 2011.11.30
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Abstract

Milk thistle (silybum marianum) is a famous dietary supplement widely used in the United States and Europe. Silbinin is a major biologically active compound of milk thistle and has strong antioxidant and radical scavenger activities. Anticancer activities, as well as chemopreventive effects on various cancer cell lines, including prostate, lung, colon, skin, and bladder, have also been reported in silbinin. In the present study, we investigated the anticancer effects of silibinin and apoptosis through cell cycle arrest on prostate cancer cell PC-3. We performed cell viability by MTT assay and western blotting to confirm cell cycle check point proteins such as cyclin A/D1/E and cyclin-dependent kinase (CDK) 2/4/6. To quantify silibinin-induced apoptotic cell death of PC-3, Annexin V and PI double staining was performed by flow cytometry, by which its cell distribution was determined. As a result, silibinin inhibited the cell growth of PC-3 cells in a time- and dose-dependent manner, and its treatment resulted in cell cycle arrest at the G1 phase. Also the level of cell cycle check point proteins (cyclin, CDK) was decreased by silibinin in a dose-dependent manner. Taken together, we suggest that apoptosis of prostate cancer cell line PC-3 induced by silibinin is associated with cell cycle arrest through decrease of cell cycle check point proteins, caspase-3 activation and poly (ADP-ribose) polymerase (PARP) cleavage.

Silibinin은 milk thistle에서 분리된 주된 생리활성 성분으로 강력한 항산화제, 항암활성에 대해서 보고되어 있다. 하지만 항암활성에 대한 정확한 기전에 대해서는 밝혀져 있지 않다. 본 연구에서는 인간 전립선 암세포주인 PC-3 세포를 이용하여 세포사멸의 기전을 조사하였다. MTT assay를 통해 세포독성을 확인하였고, PI 염색을 통해 세포주기를 확인하고, Annexin-V/PI 염색을 통한 세포사멸을 확인하였다. 뿐만 아니라 western blot을 이용하여 세포주기 및 세포사멸에 관련된 단백질 발현 정도를 확인하였다. 본 연구의 결과에서 silibinin은 인간 전립선 암세포주인 PC-3 세포에서 세포주기관련 단백질의 발현을 조절하여 세포주기 진행을 억제함으로써 세포사멸을 유도 함을 알 수 있었다.

Keywords

References

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