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Diosgenin Enhances the Sensitivity to Methotrexate Through Oxidative DNA Damage in Saos-2 Osteosarcoma Cancer Cells

Hadi Ghobadi1, Amir Valizadeh2,3, Mohsen Dashti2,4

  • 1Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran (the Islamic Republic of).

Drug Research
|November 18, 2025
PubMed

Insights

Diosgenin enhances chemotherapy effectiveness for osteosarcoma by boosting methotrexate-induced apoptosis and DNA damage in Saos-2 cells. This suggests diosgenin as a potential adjuvant therapy to improve treatment outcomes.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Diosgenin, a steroidal saponin, shows therapeutic promise for osteosarcoma.
  • The precise mechanisms of diosgenin's action in osteosarcoma remain unclear.
  • Understanding diosgenin's role in chemotherapy is crucial for improving osteosarcoma treatment.

Purpose of the Study:

  • To investigate diosgenin's effect on methotrexate-induced apoptosis in Saos-2 osteosarcoma cells.
  • To elucidate the role of DNA damage in diosgenin's augmentation of methotrexate's efficacy.
  • To assess diosgenin as a potential adjuvant therapy for osteosarcoma.

Main Methods:

  • Cell viability was assessed using the MTT assay.
  • DNA damage was evaluated by measuring γ-H2AX protein expression via Western blot.
  • Apoptosis levels, 8-oxo-2'-deoxyguanosine quantity, and cell death were analyzed using flow cytometry and ELISA.

Main Results:

  • Combining methotrexate and diosgenin significantly reduced Saos-2 cell proliferation compared to single treatments.
  • The combination therapy markedly increased apoptosis and DNA damage markers (γ-H2AX and 8-oxo-2'-deoxyguanosine).
  • Diosgenin potentiated methotrexate-induced apoptosis through enhanced DNA damage pathways.

Conclusions:

  • Diosgenin significantly augments methotrexate-mediated apoptosis in osteosarcoma cells via enhanced DNA damage.
  • Diosgenin shows potential as an adjuvant agent to improve methotrexate-based chemotherapy efficacy in osteosarcoma.
  • This combination may allow for reduced drug doses and toxicity while maintaining therapeutic effectiveness.

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