Diosgenin promotes cisplatin-induced apoptosis through oxidative DNA damage in A549 non-small cell lung cells.

Abstract

The efficacy of cisplatin-based chemotherapy in malignancy is limited by the occurrence of innate and acquired drug resistance. Clinical observations suggest that targeting phytopharmaceuticals is the right choice to enhance the effectiveness of conventional chemotherapy. We aimed to evaluate the effects of diosgenin (DG) combined with cisplatin on apoptosis and its underlying mechanisms in the A549 non-small cell lung cells. Cell viability was measured using an MTT assay. Western blot was used for the measurement of γ-H2AX and 8-Hydroxy-2'-deoxyguanosine expression level. DCFH-DA fluorescence dye was used to detect reactive oxygen species(ROS) in cells. The activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione S-transferase were also assessed. For evaluation of apoptosis,TUNEL assay was used. DG significantly increases the cytotoxic effects of cisplatin. Besides, DG considerably increased the expression levels ofγ-H2AX in cells. Upon melatonin treatment, ROS levels were increased, and antioxidant enzymes expression levels were significantly decreased. Co-treatment of DG and cisplatin resulted in increased cellular cytotoxicity through increasing ROS levels, inducing oxidative DNA damage, and decreasing cellular antioxidant defense, hence led to potent induction of apoptosis in tumor cells.