Dehydrocostus lactone induces apoptosis and mitophagy in gastric cancer cells through the ROS-mediated mitochondrial pathway

Dehydrocostus lactone (Dehy) is a sesquiterpenoid compound extracted from the dried roots of Aucklandia lappa Decne, a plant in the Compositae family, and has been shown to have significant efficacy in anti-tumor and gastrointestinal diseases. However, the anti-cancer molecular mechanisms of Dehy in gastric Cancer (GC) are unclear, and further in-depth studies are needed to elucidate its potential molecular pathways and therapeutic capabilities. This study systematically studied the anti-GC effect of Dehy and its molecular mechanism by integrating network pharmacology (NP) prediction and in vitro experimental verification strategies. The effects of the compound on proliferation, Apoptosis, and expression of Mitophagy marker proteins in GC cells were evaluated by CCK-8 assay, plate cloning assay, flow cytometry, and Western blotting techniques. NP analysis revealed its potential targets and key signaling pathways, which were further verified by experiments such as mitochondrial membrane potential detection and Reactive Oxygen Species (ROS) level determination. The results showed that Dehy significantly inhibited the proliferation of GC cells and caused changes in cell morphology. Its mechanism of action involves promoting the accumulation of intracellular ROS, thereby activating mitochondria-dependent Apoptosis pathways and Mitophagy processes. Notably, ROS is a therapeutic target for Dehy, and the mitochondrial pathway is its key mechanism of action in this context. The results confirm that Dehy is a potential drug for the treatment of GC.

Dehydrocostus lactone; Gastric cancer; Mitochondrial pathway; Mitophagy; Network pharmacology; ROS.