Raddeanoside R7 inhibits proliferation and migration of ovarian cancer cells through P13K-AKT signaling

Abstract Background Ovarian cancer remains a therapeutic challenge due to high recurrence rates and chemoresistance, necessitating novel agents from natural sources. In our previous work, a triterpenoid saponin Raddeanoside R7 (R7) was isolated and characterized from Pulsatilla cernua (Thunb.) Bercht. ex J. Presl (P. cernua). Here, R7 was investigated for its anti-ovarian cancer potential. Methods The cytotoxic effects of R7 on Caov3 and OVCAR3 cells were evaluated using the CCK-8 assay. Cell migration was assessed via the Transwell migration assay. Flow cytometry was employed to analyze cell cycle distribution and apoptosis. The role of reactive oxygen species (ROS) production in R7’s inhibitory effects was investigated through fluorometric analysis using the DCFH-DA probe. The underlying mechanisms were further explored through integrated transcriptomics and network pharmacology, with core targets validated by molecular docking. The effect of R7 on underlying signaling pathway was examined by western blotting. Results R7 exhibited potent cytotoxicity against Caov3 and OVCAR3 cells, with half-maximal inhibitory concentrations (IC50) values of 7.27 µM and 8.25 µM, leading to significant inhibition of cell viability. The Transwell migration assay showed that R7 treatment reduced the number of migrated cells by over 60%. Flow cytometry analysis revealed that R7 induced S phase cell cycle arrest and promoted apoptosis, with early and late apoptosis rates increasing to a total of approximately 68% and 29.9% of Caov3 and OCVAR3 cells, respectively. Furthermore, ROS production was identified as a key mediator of these inhibitory effects. Integrated analysis identified CCND2 and HSPA8 as core targets, which was confirmed by molecular docking. Counterintuitively, activation of the PI3K-AKT pathway was found to potentially mediate the therapeutic effects of R7. Conclusions R7 acts as a novel agent against ovarian cancer by inhibiting proliferation and migration, inducing S phase arrest and apoptosis, and elevating ROS levels. Its anti-tumor effects are potentially mediated through a context-dependent activation of the PI3K-AKT pathway, nominating R7 as a promising therapeutic candidate for further investigation.