Corn Husk Ferulic Acid Induces Apoptosis of Breast Cancer Cells via ROS-Mediated Signaling Pathways

Ferulic acid (FA) is a common phenolic acid in plants and is known to effectively combat cancer; however, the precise mechanism is still unknown. In this study, we examined the effect of FA on breast cancer (BC) cells, together with its molecular mechanism. We observed that FA greatly decreased BC cell viability without any obvious inhibitory effects on normal cell viability. Further, FA could significantly lead to the apoptosis of MDA-MB-231 cells. FA administration dramatically increased the levels of reactive oxygen species (ROS) in MDA-MB-231 cells, and mitochondria-dependent apoptosis occurred via the MAPK/STAT3/NF-κB pathways. It was also demonstrated that with an increase in FA treatment time, the G2/M phase ratio increased and the expression of p-AKT and cycle-related proteins was inhibited. The migration of MDA-MB-231 cells was significantly inhibited after FA treatment. FA reduced N-cadherin, vimentin, and SNAI 1 expression levels through the MAPK signaling pathway. Pretreatment with N-acetylcysteine and MAPK inhibitors (SP600125 or SB203580) increased the expression of these proteins, whereas pretreatment with the MAPK inhibitor (FR180204) decreased their expression. In conclusion, FA can increase ROS levels, induce mitochondria-dependent apoptosis, block the G2/M phase cycle, and inhibit cell migration. Thus, FA may be a promising new medication in the treatment of BC.