Hirsutolide isolated from Arctotis fastuosa induces apoptosis and inhibits viability, migration, and invasion of MCF-7 breast cancer cell

Breast cancer represents the most prevalent malignancy in the female population, significantly contributing to cancer-related mortality rates. However, the excessive consumption of anticancer therapies may result in adverse effects. Therefore, developing natural materials exhibiting superior anticancer properties holds significant relevance. In this study hirsutolide, a sesquiterpene lactone, was isolated from aerial parts of the Egyptian plant Arctotis fastuosa. The phytochemical analysis resulted in the effective isolation and structural confirmation of hirsutolide, which was identified using a range of spectroscopy techniques. The cytotoxicity assay revealed that hirsutolide had strong cytotoxicity against MCF-7 breast cancer cells with (IC₅₀ = 62.3 µM), while exhibiting slighter toxicity towards MRC-5 cells (IC₅₀ = 155.1 µM). Using annexin V-FITC assay, treatment of MCF7 cells with 31.1 µM for 48 h resulted in a significant increase in total apoptosis percentage from 39 % to 60 %. Additionally, Caspase 3 expression level was increased after treatment. Moreover, hirsutolide effectively inhibited cell migration and invasion in MCF-7 cells. Docking studies suggested that hirsutolide binds to the Bcl2 active site, potentially influencing apoptotic pathways. These findings highlight hirsutolide's promising potential as a therapeutic agent in breast cancer treatment.