Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Pristimerin Inhibits Breast Cancer Cell Migration by Up-regulating Regulator of G Protein Signaling 4 Expression

  • Mu, Xian-Min (Jiangsu Center of Drug Screening, China Pharmaceutical University) ;
  • Shi, Wei (Department of New Drug Screening, Jiangsu Chia-tai Tianqing Pharmaceutical Co., Ltd,) ;
  • Sun, Li-Xin (Jiangsu Center of Drug Screening, China Pharmaceutical University) ;
  • Li, Han (Jiangsu Center of Drug Screening, China Pharmaceutical University) ;
  • Wang, Yu-Rong (Jiangsu Center of Drug Screening, China Pharmaceutical University) ;
  • Jiang, Zhen-Zhou (Jiangsu Center of Drug Screening, China Pharmaceutical University) ;
  • Zhang, Lu-Yong (Jiangsu Center of Drug Screening, China Pharmaceutical University)
  • Published : 2012.04.30
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Abstract

Background/Aim: Pristimerin isolated from Celastrus and Maytenus spp can inhibit proteasome activity. However, whether pristimerin can modulate cancer metastasis is unknown. Methods: The impacts of pristimerin on the purified and intracellular chymotrypsin proteasomal activity, the levels of regulator of G protein signaling 4 (RGS 4) expression and breast cancer cell lamellipodia formation, and the migration and invasion were determined by enzymatic, Western blot, immunofluorescent, and transwell assays, respectively. Results: We found that pristimerin inhibited human chymotrypsin proteasomal activity in MDA-MB-231 cells in a dose-dependent manner. Pristimerin also inhibited breast cancer cell lamellipodia formation, migration, and invasion in vitro by up-regulating RGS4 expression. Thus, knockdown of RGS4 attenuated pristimerin-mediated inhibition of breast cancer cell migration and invasion. Furthermore, pristimerin inhibited growth and invasion of implanted breast tumors in mice. Conclusion: Pristmerin inhibits proteasomal activity and increases the levels of RGS4, inhibiting the migration and invasion of breast cancer cells.

Keywords

References

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