The effect of diosgenin on increasing the sensitivity to methotrexate through oxidative DNA damage in Saos-2 cancer cells

Abstract

Recently, various studies have focused on the therapeutic potential of diosgenin, one as a steroidal saponin, in various human malignancies, including osteoscleroma. However, the underlying mechanisms in diosgenin-mediated anticancer effects are still not fully understood. Therefore, the present study investigated the effect of diosgenin on methotrexate-induced apoptosis through DNA damage in Saos-2 cells. Methods: Saos-2 cells were treated with methotrexate, diosgenin and a combination of both, and cell viability was evaluated by MTT method. The expression of γ-H2AX protein, one of the important markers of DNA damage, was evaluated using western blot. ELISA method was used to measure the amount of 8-oxo-dG. Apoptosis was also investigated by flow cytometry. Results: Methotrexate resulted in significant inhibition of cell proliferation in a dose-dependent manner. The combination of diosgenin and methotrexate resulted in significant inhibition of proliferation compared to single treatments (P<0.05). Diosgenin also induced apoptosis through increased expression of γ-H2AX and increased levels of 8-oxo-dG. Furthermore, diosgenin increased methotrexate-induced apoptosis in Saos-2 cells.