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http://dx.doi.org/10.7314/APJCP.2012.13.4.1097

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)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.13, no.4, 2012 , pp. 1097-1104 More about this Journal
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
Pristimerin; anti-cancer; proteasome inhibition; RGS4; breast cancer;
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