Journal of Plant Biotechnology

The Korean Society of Plant Biotechnology (한국식물생명공학회)
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Extract from the branches of Rhamnus yoshinoi exerts anti-cancer effects on human prostate cancer cells through Wnt/β-catenin proteasomal degradation and identification of compounds by GC/MS

짝자래나무[Rhamnus yoshinoi] 가지 추출물에 의한 전립선암세포의 Wnt/β-catenin 분해 유도 활성 및 GC/MS 분석

  • Kang, Yeongyeong (Forest Medicinal Resources Research Center, National Institute of Forest Science) ;
  • Eo, Hyun Ji (Forest Medicinal Resources Research Center, National Institute of Forest Science) ;
  • Kim, Da Som (Forest Medicinal Resources Research Center, National Institute of Forest Science) ;
  • Park, Youngki (Forest Medicinal Resources Research Center, National Institute of Forest Science) ;
  • Park, Gwang Hun (Forest Medicinal Resources Research Center, National Institute of Forest Science)
  • 강연경 (국립산림과학원 산림약용자원연구소) ;
  • 어현지 (국립산림과학원 산림약용자원연구소) ;
  • 김다솜 (국립산림과학원 산림약용자원연구소) ;
  • 박영기 (국립산림과학원 산림약용자원연구소) ;
  • 박광훈 (국립산림과학원 산림약용자원연구소)
  • Received : 2021.04.30
  • Accepted : 2021.06.11
  • Published : 2021.06.30
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Abstract

We evaluated the anti-cancer activity against human prostate cancer cells and the associated molecular mechanism of extracts from the branches of Rhamnus yoshinoi (RYB). Treatment with RYB suppressed viability of human prostate cancer cells (PC-3) and decreased protein levels of both β-catenin and T-cell factor 4 (TCF4). This was reflected in reduced TCF4 mRNA, but not decreased β-catenin mRNA. PC-3 cells were pretreated with the proteosome inhibitor MG132 before treatment with RYB, which blocked RYB-mediated down regulation of β-catenin in PC-3 cells, thus confirming that RYB promotes the proteasomal degradation of β-catenin. RYB induced β-catenin phosphorylation, and GSK-3β inhibition by LiCl blocked the phosphorylation and proteasomal degradation of β-catenin by RYB. These results suggest that GSK-3β may be an important upstream kinase for RYB-mediated regulation of β-catenin. Finally, GC/MS analysis of RYB identified 18 compounds. Based on these findings, RYB shows potential for development as a therapeutic agent for prostate cancer.

본 연구에서는 갈매나무과에 속하는 Rhamnus yoshinoi (RY, 짝자래나무) 가지 부위의 70% 에탄올 추출물을 이용하여 전립선암세포의 항암 활성을 규명하고자 하였다. 짝자래 나무 가지 추출물을 전립선암 세포 PC-3에 처리하여 β-catenin과 TCF4의 단백질 수준 감소를 확인하였다. 이후, β-catenin과 TCF4의 mRNA 발현을 조사한 결과 β-catenin은 감소하지 않았고, TCF4는 감소하였다. 이를 통해, β-catenin mRNA의 발현에는 영향이 없지만, TCF4 mRNA 발현은 억제하는 것으로 나타났다. 단백질 분해효소억제제인 MG132를 처리한 전립선암 세포 PC-3에서 단백질 수준 확인을 통해 β-catenin의 단백질 분해를 유도할 수 있음을 확인하였다. 또한 전립선암 세포 PC-3에서 짝자래나무 가지 추출물의 GSK-3β 유도 β-catenin 단백질 분해 Kinase 구명과 β-catenin 인산화에 영향을 미치는 것을 확인하였다. 이상의 연구 결과로 짝자래나무 가지 추출물은 GSK-3β 의존성 Wnt/β-catenin 단백질의 분해를 통해 전립선암의 생육 억제와 관련이 있는 것으로 확인된다. 또한 짝자래나무 가지 추출물에서 항암활성과 관련된 활성물질이 있는 것으로 확인되었다. 본 결과는 전립선암의 항암제 개발을 위한 소재로 짝자래나무 가지 추출물의 활용이 가능할 것으로 판단된다.

Keywords

Acknowledgement

본 연구는 2021년도 국립산림과학원 일반연구과제 '갈매나무과 식물의 항염증 물질 탐색 및 약리기전 연구(과제번호: FP0400-2019-01)' 의해 이루어진 것으로 이에 감사드립니다.

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