Unveiling the Dual Mechanisms of Solanum nigrum L. Fractions Against Ovarian Cancer via AKT/NF-κB and Tumor Microenvironment Modulation: An In Silico and In Vitro Study.

Ovarian cancer treatment remains challenging due to aggressive metastasis and the complex tumor microenvironment (TME). Solanum nigrum L. (SN), a berry-bearing plant rich in bioactive phytochemicals, offers promising multi-target anticancer potential. This study elucidated the systemic molecular mechanisms of SN fractions against ovarian cancer by integrating network pharmacology, molecular docking, and in vitro models. In silico analyses and molecular docking identified apoptosis, metastasis-related pathways, and NF-κB (RELA) as core targets. For in vitro validation, butanol (SNBT) and methylene chloride (SNMC) fractions of SN were evaluated in SKOV3 cells. SNBT significantly induced caspase-3-dependent apoptosis, while SNMC effectively suppressed cancer cell migration and invasion without cytotoxicity. Furthermore, both fractions markedly downregulated phosphorylated AKT and NF-κB, experimentally confirming the suppression of the AKT/NF-κB signaling axis. Crucially, in a tumor-associated macrophage co-culture model, SNMC attenuated the pro-metastatic TME by reducing MMP2, MMP9, and VEGF secretion. Conclusively, SN exerts potent anticancer effects through distinct fractional activities, such as driving apoptosis and blocking metastasis, mediated via AKT/NF-κB inhibition and TME remodeling. These findings highlight SN-derived fractions as promising multi-target therapeutic candidates against ovarian cancer.