Anti-metastatic properties of the triterpene diosgenin on lung carcinoma cells

Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung carcinoma (NSCLC) accounting for ~85% of all cases. Although chemotherapy is a standard treatment option, its success is limited by dose-dependent toxicity and the development of chemoresistance. These challenges have increased interest in phytochemicals such as triterpenes, natural metabolites with broad pharmacological activities and potential anticancer properties. Diosgenin (Dios), a steroidal triterpene present in numerous medicinal plants, has been reported to modulate pathways central to cancer cell survival and metastasis. This study evaluated the effects of Diosgenin on NSCLC cells to elucidate its mechanism of action. Diosgenin demonstrated strong cytotoxic activity in the micromolar range in a dose-dependent manner within 24 hours. Functional assays showed that Diosgenin significantly inhibited A549 cell migration and induced cell cycle arrest at the S and G2/M phases. Protein analysis revealed reduced expression of proliferative and survival markers, including Ki67, MAPK, and PI3K, accompanied by a notable increase in Caspase 3/7 activation. Metastasis-related gene expression profiling showed that Diosgenin downregulated key pro-metastatic genes such as MMP2, MMP9, and PREX1, all of which contribute to extracellular matrix degradation, cytoskeletal remodeling, and invasive potential. In contrast, Diosgenin upregulated NDRG1, a well-established metastasis suppressor involved in inhibiting epithelial-to-mesenchymal transition and limiting cell motility. Collectively, these findings indicate that Diosgenin exerts multi-targeted anticancer activity by suppressing proliferation, inducing apoptosis, and significantly impairing metastasis-associated pathways. Diosgenin represents a promising natural therapeutic candidate for slowing NSCLC progression and reducing metastatic potential. Acknowledgement: This research was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20GM103475.