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

Abstract 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 3 H 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.