Breast cancer is one of the most commonly diagnosed cancers worldwide. It is a leading cause of cancer mortality among women globally. Mocetinostat (MGCD0103), a histone deacetylase inhibitor (HDACi), has antitumor effects on various cancers. However, its role in breast cancer is not well understood. This research aims to clarify some of mocetinostat’s mechanisms of action in cancer cell proliferation and to understand the relationship between reactive oxygen species (ROS)/mitogen-activated protein kinase (MAPK), which are active in autophagy and autophagic cell death. Mocetinostat reduced cell proliferation in a dose- and time-dependent manner, as shown by MTT assays after 48 h of treatment. Additionally, wound healing assays indicated that mocetinostat has an anti-proliferative effect. The effect of mocetinostat on ROS accumulation was determined using a ROS assay kit, and its autophagic effect was determined using an autophagy kit. The effect of mocetinostat on MAPK signaling was evaluated through Western blotting. Mocetinostat suppressed the proliferation and migration of SKBR-3 cells, while increasing ROS accumulation and inducing autophagy. Mocetinostat treatment in SKBR-3 cells led to the downregulation of PI3K, AKT (Protein kinase B, PKB), SAPK1/2 (stress-activated protein kinases), c-JUN, (Cellular Jun proto-oncogene transcription) and the upregulation of P53 and ATG5 (Autophagy-Related Genes) thereby induce cell death. This study presents recent research evidence on HDACi-mediated autophagic pathways, particularly the ROS/MAPK pathway. Mocetinostat suppressed the proliferation of breast cancer cells in vitro through a ROS-mediated autophagy mechanism using the MAPK pathway. Investigating the mechanism of mocetinostat may provide a novel therapeutic approach for breast cancer treatment.
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