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인간 대장암 세포에 대한 먹넌출 추출물의 GSK3β 의존성 threonine-286 인산화를 통한 Cyclin D1 분해 KCI 등재

Berchemia floribunda-mediated Proteasomal Degradation of CyclinD1 via GKS3β-dependent Threonine-286 Phosphorylation in Human Colorectal Cancer Cells

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한국자원식물학회지 (Korean journal of plant resources)
한국자원식물학회 (The Plant Resources Society Of Korea)
초록

이상의 연구 결과로 먹넌출 열매 추출물은 GSK3β 의존성 Cyclin D1 단백질의 분해를 통해 대장암세포의 생육 억제와 관련이 있는 것으로 확인된다. 본 결과는 대장암의 항암제 개발을 위한 소재로 먹넌출 열매의 활용이 가능할 것으로 판단된다.

In this study, we evaluated the anti-cancer activity and potential molecular mechanism of 70% ethanol extracts of the Berchemia floribunda (BF) which belongs to Rhamnaceae against human colorectal cancer cells. The treatment of BF decreased the cell proliferation in HCT116 cell and suppressed cellular accumulation of Cyclin D1 protein. Inhibition of proteasomal activity by MG132 attenuated BF-mediated Cyclin D1 downregulation and Cyclin D1 was decreased in the cell treated with BF. These findings indicates that BF-mediated Cyclin D1 downregulation may be result from Cyclin D1 proteasomal degradation. Additionally, BF-mediated Cyclin D1 degradation was blocked in the presence of LiCl, a GSK3β inhibitor, but not PD98059, SP600125, SB203580, Bay11-7082, LY294002 an ERK1/2 inhibitor, JNK inhibitor, p38 inhibitor, IκK inhibitor and PI3K inhibitor. Furthermore, BF phosphorylated Cyclin D1 at threonine-286 (Thr286), and LiCl-induced GSK3β inhibition reduced the BF mediated phosphorylation of Cyclin D1 at Thr286. These results suggested that BF may downregulate Cyclin D1 expression as a potential anti-cancer target through GSK3β dependent Cyclin D1 degradation. Therefore, this study provides that the extract of BF has anticancer activity against human colorectal cancer cells.

목차
Abstract
서언
재료 및 방법
    실험재료
    추출물 제조
    세포 배양 및 세포 생육 억제 활성 측정
    SDS-PAGE 및 western blot 분석
    Reverse transcriptase-polymerase chain reaction (RT-PCR)
    통계분석
결과 및 고찰
    먹넌출 추출물 처리에 따른 대장암세포의 세포생존율
    먹넌출 열매 추출물의 Cyclin D1 단백질 수준 감소 및 단백질 분해 유도활성
    먹넌출 열매 추출물의 GSK3β 유도 Cyclin D1 단백질 분해 Kinase 구명
적요
References
저자
  • 강연경(국립산림과학원 산림약용자원연구소) | Yeongyeong Kang (Forest Medicinal Resources Research Center, National Institute of Forest Science)
  • 어현지(국립산림과학원 산림약용자원연구소) | Hyun Ji Eo (Forest Medicinal Resources Research Center, National Institute of Forest Science)
  • 김다솜(국립산림과학원 산림약용자원연구소) | Da Som Kim (Forest Medicinal Resources Research Center, National Institute of Forest Science)
  • 박영기(국립산림과학원 산림약용자원연구소) | Youngki Park (Forest Medicinal Resources Research Center, National Institute of Forest Science)
  • 송정호(국립산림과학원 산림소득자원연구과) | Jeong Ho Song (Division of Special Forest Product, National Institute of Forest Science)
  • 박광훈(국립산림과학원 산림약용자원연구소) | Gwang Hun Park (Forest Medicinal Resources Research Center, National Institute of Forest Science) 교신저자