Luteolin exerts anti-tumor activity through the suppression of epidermal growth factor receptor-mediated pathway in MDA-MB-231 ER-negative breast cancer cells

摘要

This study investigated the inhibitory effect of luteolin on MDA-MB-231 estrogen receptor (ER) negative breast tumor growth both in vitro and in vivo. Study results showed that luteolin suppresses 3H thymidine incorporation indicating cell growth inhibition, and this was accompanied by cell cycle arrest at the G2/M and S stages and apoptotic activity. Further analyses showed that luteolin exhibited cell cycle arrest and apoptotic activity by decreasing AKT, PLK1, cyclin B 1, cyclin A, CDC2, CDK2, and Bcl-xL expression and increasing p21 and Bax expression. Underlying mechanisms of action exerted by luteolin included the down-regulation. EGFR mRNA expression followed by the inhibition of EGF-induced MAPK activation, including the phosphorylation of ERK, p38 and AKT. Luteolin-supplementation at 0.01% or 0.05% significantly reduced tumor burden in nude mice inoculated with MDA-MB-231 cells. In conclusion, luteolin effectively suppresses MDA-MB-231 ER-negative breast cancer cell growth, and its anticancer activity may be partly derived from inhibitory effects on EGFR-mediated cell survival.