Pristimerin Inhibits Breast Cancer Cell Migration by Upregulating Regulator of G Protein Signaling 4 Expression

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 pristimerinon the purified and intracellular chymotrypsin proteasomal activity, the levels of regulator of G protein signaling4 (RGS 4) expression and breast cancer cell lamellipodia formation, and the migration and invasion weredetermined by enzymatic, Western blot, immunofluorescent, and transwell assays, respectively.
Results: We foundthat pristimerin inhibited human chymotrypsin proteasomal activity in MDA-MB-231 cells in a dose-dependentmanner. Pristimerin also inhibited breast cancer cell lamellipodia formation, migration, and invasion in vitroby up-regulating RGS4 expression. Thus, knockdown of RGS4 attenuated pristimerin-mediated inhibition ofbreast cancer cell migration and invasion. Furthermore, pristimerin inhibited growth and invasion of implantedbreast tumors in mice.
Conclusion: Pristmerin inhibits proteasomal activity and increases the levels of RGS4,inhibiting the migration and invasion of breast cancer cells.

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