Alkaloids isolated from Scutellaria Barbata D. Don trigger apoptosis and inhibit migration by modulating the p38-p53 pathway in ovarian cancer.

BACKGROUND: Ovarian cancer is a widely prevalent gynecological malignancy associated with significant morbidity and mortality. Scutellaria barbata D. Don (SB), a traditional Chinese medicine, has been reported to have diverse biological effects, including anti-ovarian cancer effects. However, the specific effects and underlying mechanism of the alkaloid fraction, the active fraction isolated from SB, in ovarian cancer remain unclear. This study aimed to explore the anti-tumor effects and underlying mechanisms of the alkaloid fraction of Scutellaria barbata D. Don (SBA) in ovarian cancer. METHODS: SBA was extracted by alcohol solvent extraction, and its chemical composition was analyzed using chromogenic reaction and high-pressure liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC/Q-TOF-MS). The effects of SBA on the proliferation, migration and apoptosis of human ovarian cancer cells (SKOV3) were detected by CCK-8 assay, clone formation assay, scratch assay, transwell assay, flow cytometry, Hoechst 33,342 staining and Western blot. SKOV3 xenograft nude mouse model was established to further investigate the in vivo effects of SBA. Serum and tissue samples were collected for molecular-biological indicators, and pathological changes were evaluated by hematoxylin-eosin, immunohistochemistry, and Western blot. RESULTS: A total of 38 nitrogen-containing compounds were detected in SBA. SBA inhibited the proliferation and migration of SKOV3 cells in a dose-dependent manner, in addition to inducing significant cell apoptosis. In the SKOV3 xenograft model, SBA attenuated ovarian cancer tumor growth with no significant organ toxicity. The anti-tumor effects of SBA were associated with downregulation of Bcl-2, N-cadherin, MMP2, MMP9, and upregulation of Bax, cleaved caspase-3/ caspase-3, cleaved caspase-9, E-cadherin, P-p38/ p38, and P-p53/ p53 both in vitro and in vivo. Additionally, SBA exhibited synergy with cisplatin (DDP) and alleviated cisplatin-induced renal damage. CONCLUSION: SBA suppresses ovarian cancer by triggering apoptosis and inhibiting cell migration via the p38-p53 pathway. Combining SBA with DDP reduces drug toxicity and potentiates the anti-tumor effects. Therefore, SBA is a promising candidate for treating ovarian cancer, and mitigating the toxic side effects of DDP in ovarian cancer.