The anti-proliferative activity of ursolic acid in MDA-MB-231 human breast cancer cells. - GreenMedInfo Summary

The potential mechanisms of action of ursolic acid (UA) in regulating cell proliferation in MDA-MB-231 human breast cancer cells through Nrf2 pathway were investigated. UA significantly inhibited the proliferation of MDA-MB-231 cells at dose≥10 µM in a dose-dependent manner, and no cytotoxicity was observed at concentrations below 29.87 ± 2.60 µM. The expressions of Nrf2 and p-Nrf2 in whole cell and nucleus, and NQO1 were inhibited by UA treatment, while the Keap1 expression was upregulated. No significant difference was observedin Nrf2 mRNA levels, indicating that UA reduced Nrf2 expression not through mRNA but a post-translational mechanism. Additionally, EGF-induced p-Nrf2 and its downstream NQO1 and SOD1 enzymes were abolished by UA. However, EGF or p-EGFR had no effect on the expressions of Keap1. These results suggested that the proliferative inhibitory effect of UA might be partially through down-regulating Nrf2 via Keap1/Nrf2 pathway and EGFR/Nrf2 pathway in MDA-MB-231 cells.