1-Dehydro-6-Gingerdione Exerts Anticancer Effects on MDA-MB-231 Cells and in the Xenograft Mouse Model by Promoting the Ferroptosis Pathway.

Breast cancer (BC) is the most prevalent malignancy among women, with millions of newly diagnosed cases emerging annually. Therefore, identifying novel pharmaceuticals for therapeutic purposes is imperative. Several natural compounds and their products have demonstrated potential in the treatment of cancer. This study examined the effects of the ginger derivative 1-dehydro-6-gingerdione (1-D-6-G) on BC and its mechanisms of action. MTT and colony formation assays were used to check the anticancer effect of 1-D-6-G. Then the anticancer mechanism of 1-D-6-G was predicted using proteomics analysis. The molecular pathway was verified by qRT-PCR and immunobloting analysis. Additionally, the anticancer properties of 1-D-6-G were investigated in vivo using xenograft mice model. Finally, an in silico study was conducted to examine the interaction of 1-D-6-G and pathway-related proteins. MTT and colony formation assay results indicated that 1-D-6-G has potent cytotoxic properties against BC cells. Proteomic analysis revealed that the anticancer mechanism of 1-D-6-G on MDA-MB-231 cells is associated with the ferroptosis signaling pathway. In addition, qRT-PCR and immunoblotting analyses revealed that the cytotoxic effects of 1-D-6-G on MDA-MB-231 cells were associated with ferroptosis signaling induction. Our in vivo results further confirmed the in vitro findings. The administration of 1-D-6-G for 14 days exhibited anticancer properties in xenograft mice by stimulating the ferroptosis pathway without causing damage to essential organs such as the liver and kidneys. Additionally, in silico results confirmed the structural stability of the molecular interaction between 1-D-6-G and ferroptosis target proteins. Our findings indicate that 1-D-6-G has the potential to serve as a novel therapeutic agent for inhibiting BC progression by targeting the ferroptosis pathway.