Cryptocaryone (
CPC) was previously reported as preferential for killing natural products in
oral cancer cells. However, its radiosensitizing potential combined with ultraviolet C (UVC) cell killing of
oral cancer cells remains unclear. This study evaluates the combined anti-proliferation effect and clarifies the mechanism of combined UVC/
CPC effects on
oral cancer cells. UVC/
CPC shows higher anti-proliferation than individual and control treatments in a low cytotoxic environment on normal oral cells. Mechanistically, combined UVC/
CPC generates high levels of
reactive oxygen species and induces
mitochondrial dysfunction by generating mitochondrial
superoxide, increasing mitochondrial mass and causing the potential destruction of the mitochondrial membrane compared to individual treatments. Moreover, combined UVC/
CPC causes higher G2/M arrest and triggers apoptosis, with greater evidence of cell cycle disturbance,
annexin V, pancaspase,
caspases 3/7 expression or activity in
oral cancer cells than individual treatments. Western blotting further indicates that UVC/
CPC induces overexpression for cleaved types of
poly (ADP-ribose) polymerase and
caspase 3 more than individual treatments. Additionally, UVC/
CPC highly induces γH2AX and
8-hydroxy-2'-deoxyguanosine adducts as DNA damage in
oral cancer cells. Taken together,
CPC shows a radiosensitizing anti-proliferation effect on UVC irradiated
oral cancer cells with combined effects through oxidative stress, apoptosis and DNA damage.