Korean Journal of Medicinal Crop Science (한국약용작물학회지)

The Korean Society of Medicinal Crop Science (한국약용작물학회)
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Anti-proliferative Activity of Ethanol Extracts of Root of Aralia cordata var. continentalis through Proteasomal Degradation of Cyclin D1 in Human Colorectal Cancer Cells

독활 에탄올 추출물의 대장암 세포에서 Cyclin D1 단백질 분해 유도를 통한 세포 생육 억제활성

  • Park, Su Bin (Department of Medicinal Plant Resources, Andong National University) ;
  • Park, Gwang Hun (Forest Medicinal Resources Research Center, National Institute of Forest Science) ;
  • Song, Hun Min (Department of Medicinal Plant Resources, Andong National University) ;
  • Park, Ji Hye (Department of Medicinal Plant Resources, Andong National University) ;
  • Shin, Myeong Su (Department of Medicinal Plant Resources, Andong National University) ;
  • Son, Ho Jun (Forest Medicinal Resources Research Center, National Institute of Forest Science) ;
  • Um, Yurry (Forest Medicinal Resources Research Center, National Institute of Forest Science) ;
  • Jeong, Jin Boo (Department of Medicinal Plant Resources, Andong National University)
  • 박수빈 (안동대학교 생약자원학과) ;
  • 박광훈 (국립산림과학원 산림약용자원연구소) ;
  • 송훈민 (안동대학교 생약자원학과) ;
  • 박지혜 (안동대학교 생약자원학과) ;
  • 신명수 (안동대학교 생약자원학과) ;
  • 손호준 (국립산림과학원 산림약용자원연구소) ;
  • 엄유리 (국립산림과학원 산림약용자원연구소) ;
  • 정진부 (안동대학교 생약자원학과)
  • Received : 2017.08.19
  • Accepted : 2017.09.18
  • Published : 2017.10.30
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Abstract

Background: In this study, we evaluated the anti-cancer activity and potential molecular mechanism of 70% ethanol extracts of the root of Aralia cordata var. continentalis (Kitagawa) Y. C. Chu (RAc-E70) against human colorectal cancer cells. Methods and Results: RAc-E70 suppressed the proliferation of the human colorectal cancer cell lines, HCT116 and SW480. Although RAc-E70 reduction cyclin D1 expression at the protein and mRNA levels, RAc-E70-induced reduction in cyclin D1 protein level occurred more dramatically than that of cyclin D1 mRNA. The RAc-E70-induced downregulation of cyclin D1 expression was attenuated in the presence of MG132. Additionally, RAc-E70 reduced HA-cyclin D1 levels in HCT116 cells transfected with HA-tagged wild type-cyclin D1 expression vector. RAc-E70-mediated cyclin D1 degradation was blocked in the presence of LiCl, a $GSK3{\beta}$ inhibitorbut, but not PD98059, an ERK1/2 inhibitor and SB203580, a p38 inhibitor. Furthermore, RAc-E70 phosphorylated cyclin D1 at threonine-286 (T286), and LiCl-induced $GSK3{\beta}$ inhibition reduced the RAc-E70-mediated phosphorylation of cyclin D1 at T286. Conclusions: Our results suggested that RAc-E70 may downregulate cyclin D1 expression as a potential anti-cancer target through $GSK3{\beta}$-dependent cyclin D1 degradation. Based on these findings, RAc-E70 maybe a potential candidate for the development of chemopreventive or therapeutic agents for human colorectal cancer.

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References

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