Diosgenin enhances the effect of radiation on head and neck cancer cells through apoptosis induction, G2/M cell cycle arrest, and ROS generation.

Radiotherapy is a cornerstone in treating head and neck cancers, yet its effectiveness is often limited by factors such as hypoxia and cancer stem cells. This study evaluated the radiosensitizing potential of diosgenin in KB cancer cells and normal HDF cells exposed to 4 Gy X-rays, with or without diosgenin. Cell viability, apoptosis, cell cycle distribution, ROS production, and expression of intrinsic apoptosis-related genes were assessed using MTT assays, flow cytometry, and RT-qPCR, respectively. Diosgenin alone reduced KB cell viability and, when combined with radiation (63 μM + 4 Gy), further decreased viability to 27.93 ± 1.8%, which was significantly lower than with either treatment alone (p < 0.05), while exhibiting lower toxicity in HDF cells. Diosgenin also induced G2/M arrest and amplified radiation-induced apoptosis, sub-G1 accumulation, and ROS production. These effects correlated with a marked increase in the Bax/Bcl-2 mRNA ratio in the combination group compared to either treatment alone (p < 0.0001), indicating activation of the intrinsic apoptotic pathway. Overall, the results suggest that diosgenin enhances the effect of radiation on head and neck cancer cells and may serve as a promising adjunct to radiotherapy.