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 GSK3β 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 GSK3β 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 GSK3β-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.

서 언
 재료 및 방법
  1. 실험재료
  2. 추출물 제조
  3. 세포 생육 억제활성 측정
  4. SDS-PAGE 및 western blot 분석
  5. Reverse transcriptase-polymerase chain reaction (RTPCR)
  6. Transient transfection
  7. 통계분석
 결과 및 고찰
  1. 독활 에탄올 추출물의 대장암세포의 생육 억제와 cyclin
  2. 독활 에탄올 추출물의 cyclin D1 단백질 분해 유도활성
  3. 독활 에탄올 추출물의 GSK3β 유도 cyclin D1의threonine-286 (Thr286) 인산화 의존성 cyclin D1 단백질분해유도 활성
 REFERENCES

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