Scutellarin triggers ferroptosis in ovarian cancer cells via inhibiting AKT/mTOR and JAK2/STAT3 pathways
Ovarian cancer (OC) ranks as the second most prevalent gynecologic malignancy worldwide, largely attributed to the difficulties in detecting early stages, frequent disease reappearance, and unresponsiveness to existing therapies. Contemporary treatment selections for individuals with OC remain limited. Scutellarin (Scu), an active compound, demonstrates suppressive properties against multiplication, invasion, and survival of certain cancer cell types. Nevertheless, the exact anti-cancer properties and molecular pathways of Scu in OC are still not fully understood. This investigation sought to examine the therapeutic impact of Scu and its potential mechanisms in OC. A series of assays, encompassing cell counting kit-8 (CCK-8), colony-formation assay, EdU staining, scratch/wound healing assay, matrigel invasion assay, DHE staining, flow cytometry, Western blotting, ferrous ion content assay kit, and immunofluorescence staining were employed to investigate the role and mechanisms of Scu in OC cell lines (SKOV3 and HO-8910). Scu markedly diminished cell viability, proliferation, and colony formation in both SKOV3 and HO-8910 cells. Scu substantially inhibited OC cells' migration, invasion, and epithelial-mesenchymal transition (EMT). Additionally, the flow cytometry data and Western blot results of Bax and Bcl-2 protein levels indicated that Scu induced cell apoptosis in both SKOV3 and HO-8910 cells. Furthermore, Scu induced cell ferroptosis by upregulating the levels of reactive oxygen species (ROS), 4-hydroxynonenal (4-HNE), and Fe2+ while downregulating the expression of specificity protein 1 (SP1), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4). The anti-cancer capabilities of Scu were also linked to the inhibition of the phosphorylated forms of AKT, mTOR, JAK2, and STAT3. Lastly, cell apoptosis and ferroptosis induced by Scu were counteracted by AKT agonist SC79. The findings demonstrate that Scu effectively inhibited cell multiplication, migration, invasion, and EMT, while inducing oxidative stress, apoptosis, and ferroptosis in SKOV3 and HO-8910 cells. These effects were likely mediated by inhibiting the AKT/mTOR and JAK2/STAT3 signaling cascades. This investigation suggests that Scu holds potential as a promising chemotherapeutic agent for treating OC.