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Anti-Proliferative Activity of Ethanol Extracts from Taxilli Ramulus (Taxillus chinensis (DC.) Danser) Through Cyclin D1 Proteasomal Degradation in Human Colorectal Cancer Cells

  • 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, Su Bin (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)
  • Received : 2017.07.15
  • Accepted : 2017.10.16
  • Published : 2017.12.31

Abstract

In this study, we elucidated anti-cancer activity and potential molecular mechanism of 70% ethanol extracts from Taxilli Ramulus (Taxillus chinensis (DC.) Danser) (TR-E70) against human colorectal cancer cells. Anti-cell proliferative effect of TR-E70 was evaluated by MTT assay. The effect of TR-E70 on the expression of cyclin D1 in the protein and mRNA level was evaluated by Western blot and RT-PCR, respectively. TR-E70 suppressed the proliferation of human colorectal cancer cell lines, HCT116 and SW480. Although TR-E70 decreased cyclin D1 expression in protein and mRNA level, decreased level of cyclin D1 protein by TR-E70 more dramatically occurred than that of cyclin D1 mRNA. Cyclin D1 downregulation by TR-E70 was attenuated in presence of MG132. In addition, TR-E70 phosphorylated threonine-286 (T286) of cyclin D1. TR-E70-mediated cyclin D1 degradation was blocked in presence of LiCl as an inhibitor $GSK3{\beta}$ but not PD98059 as an ERK1/2 inhibitor and SB203580 as a p38 inhibitor. Our results suggest that TR-E70 may downregulate cyclin D1 as one of the potential anti-cancer targets through $GSK3{\beta}$-dependent cyclin D1 degradation. From these findings, TR-E70 has potential to be a candidate for the development of chemoprevention or therapeutic agents for human colorectal cancer.

Keywords

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