Erianin Disturbs Iron and ROS Homeostasis To Trigger Ferroptosis in Colorectal Cancer Cells.

Ferroptosis is a non-apoptotic, iron-dependent death form. Ferroptosis was embedded in various disorders, including cancer. Ferroptosis induction in cancerous tissues could be an alternative treatment pathway. In this study, we studied the ferroptotic impact of the natural compound erianin, besides its apoptotic effect in colorectal adenocarcinoma cell line (Caco2). The cytotoxicity of erianin was performed in the presence and in the absence of deferoxamine (DFO) as an iron chelator. We measured reactive oxygen species (ROS), apoptosis, and cell cycle using flow cytometry. Further, the change in expression of the related ferroptosis genes, including PTGS2, GPX4, and FSP1, was determined by qPCR. The obtained data displayed that the erianin triggered Caco2 cells death, apoptosis, and cell cycle. Importantly, erianin cytotoxicity in Caco2 cells decreased about 6-fold in the presence of DFO. Additionally, ROS, lipid peroxidation, and iron levels were dropped in Caco2-treated with erianin, which was previously incubated with DFO, compared to those treated with erianin only. Further, the expressions of PTGS2 and GPX4 declined with upregulation in FSP1 in Caco2-treated with erianin, which was previously incubated with DFO compared to these treated with erianin only. The collected findings from the experimental techniques could show that erianin participated in cell death by the ferroptosis pathway besides its known apoptotic effect. Taken together, erianin could serve as a prospective drug in colon cancer depending on multi-pathways.