Tabriz Valiasr International Hospital Publication International Journal of Drug Research in Clinics 2980-9835 3 1 2025 01 12 Inhibitory Effects of Diosgenin on Breast Cancer Cell Progression through Regulation of Metastatic Gene Expression e20 e20 10.34172/ijdrc.2025.e20 EN Majid Montazer https://orcid.org/0000-0001-7846-0128 Elham Jangi Mehran Molavand https://orcid.org/0009-0007-3923-7549 Bahman Yousefi https://orcid.org/0000-0002-4220-1527 Amir Valizadeh https://orcid.org/0000-0002-7852-8118 Journal Article 10.34172/ijdrc.2025.e20 2025 10 02 2025 10 29 Background: As a steroidal saponin found in numerous plants historically used in traditional healing systems, diosgenin exhibits promising activity against multiple types of cancer. While its anticancer properties are documented, its molecular mechanisms remain incompletely characterized. Accordingly, this study investigated whether diosgenin can enhance the efficacy of doxorubicin (DOX) in MCF-7 breast carcinoma cells. Methods: Following treatment with DOX, diosgenin, or their combination, MCF-7 viability was quantified using the MTT method. Then, the expression patterns of metastatic regulators (matrix metalloproteinase 2 [MMP-2], MMP-9, c-Myc, and K-Ras) were analyzed by quantitative real-time polymerase chain reaction and immunoblotting. Results: DOX demonstrated concentration-dependent growth inhibition. Moreover, combined diosgenin-DOX treatment produced superior antiproliferative effects compared to individual agents (P<0.05). Additionally, diosgenin could substantially suppress metastatic potential by downregulating MMP-2, MMP-9, c-Myc, and K-Ras expression. Ultimately, diosgenin amplified DOX-triggered programmed cell death. Conclusion: Our findings indicated that this plant-derived compound potentiates DOX anticancer activity through enhancing apoptotic response while suppressing metastasis-associated gene networks. These observations support investigating diosgenin as a complementary agent in breast malignancy management and warrant expanded biological evaluations.