Boswellia carterii n-hexane extract suppresses breast cancer growth via induction of ferroptosis by downregulated GPX4 and upregulated transferrin

Breast Cancer (BC) remains a significant health concern for women globally, prompting the relentless pursuit of novel therapeutic modalities. As a traditional Chinese medicine, Boswellia carterii has been extensively used to treat various cancers, such as BC. However, the anti-BC effect and underlying mechanism of Boswellia carterii remain largely unclear. The aim of this study is to explore the therapeutic effect of Boswellia carterii n-hexane extract (BChE) against BC as well as its underlying mechanism. The present study showed that BChE significantly suppressed the viability of human BC cells. Moreover, BChE exhibited potent anti-BC activity in vivo with no significant toxic effects. Additionally, BChE induced Ferroptosis via increased Transferrin expression and the intracellular accumulation of Fe²⁺, as well as decreased Glutathione Peroxidase 4 (GPX4) expression and the upregulation of Reactive Oxygen Species (ROS)-induced lipid peroxidation in BC cells. In vivo experimental results also demonstrated that BChE effectively induced Ferroptosis through GPX4 downregulation and Transferrin upregulation in tumor-bearing mice. Overall, BChE inhibited the growth of BC cells by inducing Ferroptosis mediated by modulating the iron accumulation pathway and the lipid peroxidation pathway. Therefore, BChE could serve as a potential ferroptosis-targeting drug for treating BC.