Lupeol inhibits the proliferation and migration of MDA-MB-231 breast cancer cells <i>via</i> a novel crosstalk mechanism between autophagy and the EMT

Abstract

Triple-negative breast cancer is the most aggressive type of breast cancer, with a poor prognosis, while effective treatment options are limited. In this study, the anti-tumor effect of lupeol, a natural triterpenoid, toward breast cancer cells and the underlying mechanisms were examined. We firstly predict the primary pathways of lupeol inhibited to TNBC by a network pharmacology approach, which indicated that lupeol may inhibit TNBC <i>via</i> multiple signaling pathways. In addition, experimental data showed that lupeol exhibited outstanding anti-proliferative and anti-metastatic abilities <i>in vitro</i> and <i>in vivo</i>. Additional intrinsic mechanism studies revealed that lupeol might induce autophagy by inhibiting the Akt-mTOR pathway, and activating an autophagy inhibited epithelial-mesenchymal transition (EMT). This study demonstrated that lupeol could inhibit TNBC cells by inducing autophagy, suggesting lupeol as a potential treatment alternative or as a dietary supplement for TNBC, as well as offering novel insights into the anti-cancer effect of lupeol.