Abstract
Pristimerin isolated from Celastrus and Maytenus spp can inhibit proteasome activity. However, whether pristimerin can modulate cancer metastasis is unknown. 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. 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. Pristmerin inhibits proteasomal activity and increases the levels of RGS4, inhibiting the migration and invasion of breast cancer cells.
Highlights
Breast cancer is the leading cause of cancer death among females in the world (Jemal et al, 2011)
We found that treatment with pristimerin directly inhibited human 20S chymotrypsinlike proteasome activity and chymotrypsin-like activity in MDA-MB-231 breast cancer cells
We found that treatment with pristimerin inhibited the migration and invasion of MDA-MB-231 cells in vitro in a dose-dependent manner and the growth and invasion of implanted breast tumors in vivo
Summary
Breast cancer is the leading cause of cancer death among females in the world (Jemal et al, 2011). Pristimerin inhibited breast cancer cell lamellipodia formation, migration, and invasion in vitro by up-regulating RGS4 expression. We examined the effect of pristimerin on 20s proteasome chymotrypsin-like activity in breast cancer cells and on the migration and invasion in vitro and in vivo.
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