Breast cancer (BC), the most aggressive cancer in women, continues to exhibit serious health concerns globally. However, the existing limitations in current therapeutics demand novel, broad-spectrum and cost-effective treatment. Herbal medicines are currently used as effective anticancer treatments, comprising specific plant-derived bioactive compounds. Jervine, a steroidal alkaloid, has proven to have anticancer activities; hence, its therapeutic mechanism in contributing to BC tumorigenesis remains incompletely elucidated. This study investigates the molecular mechanism of action of jervine’s anticancer efficacy against BC via in silico and in vitro analyses. In silico analysis, including network pharmacology, pharmacokinetics, molecular docking, and molecular dynamics simulations, was performed to explore jervine’s therapeutic potential against BC targets. Further,an invitro analysis was evaluated for its cytotoxic effects using MDA-MB-231 triple-negative breast cancer (TNBC) cells, using the MTT assay, followed by gene expression analysis via RT-PCR. The combined findings from network pharmacology, molecular docking, and molecular simulation analyses clearly demonstrated that jervine possesses favourable drug-like properties and forms stable interactions with multiple Wnt signalling targets (WNT5A, FZD5, LRP6), as well as key modulators from other pathways, including BMP4 (a member of the TGF-β family) and SHH (a central component of Hedgehog signalling), all of which are associated with breast cancer. In vitro analysis of MDA-MB-231 cells using the MTT assay showed that jervine exhibited significant cytotoxic effects, with IC 50 values of 18.55 μM at 24 h and 13.23 μM at 48 h. Further, gene expression analysis particularly emphasized that jervine significantly controlled the dysregulated WNT signalling targeted genes (Wnt 5a, DVL2, FZD5, LRP6) and including SHH, BMP4 genes mRNA expression levels and thereby inhibited the proliferation of BC cells. Further, these in vitro results coincide with the findings of the computational studies. The graphical abstract represents a research workflow that explores the anticancer effects of the compound jervine on breast cancer through various in silico and in vitro processes, including computational analysis, biological evaluation, and mechanistic insights. The illustration highlights the molecular interactions from in silico and in vitro studies of jervine's therapeutic potential in breast cancer (BC).
Eswaran et al. (Thu,) studied this question.