Dihydroquinine Enhances Radiosensitivity in Cervical Cancer Cells Accompanied by Radiation-Induced Cellular Responses

Radiosensitizers are being investigated to improve the therapeutic efficacy of radiotherapy by enhancing tumor cell sensitivity while minimizing damage to normal tissues. Dihydroquinine (DHQ), a naturally occurring Cinchona alkaloid with diverse biological activities, has not previously been evaluated for radiosensitizing potential. In this study, human cervical cancer (HeLa) cells were pretreated with an IC20 concentration of DHQ and exposed to 6 MV X-ray irradiation. Clonogenic survival was assessed after irradiation at 2, 4, and 6 Gy, while intracellular ROS, γ-H2AX immunofluorescence, and apoptosis were evaluated following DHQ pretreatment and 2 Gy irradiation. DHQ pretreatment reduced clonogenic survival, yielding sensitizer enhancement ratio values of 1.37 and 1.55 at surviving fractions of 0.20 and 0.37, respectively, indicating modest-to-moderate enhancement of radiosensitivity. DHQ was also associated with increased ROS production, elevated γ-H2AX positivity, and enhanced apoptosis compared with irradiation alone. These findings suggest that DHQ enhances the radiation response in HeLa cells and is associated with increased radiation-induced cellular responses. Although the radiosensitizing effect was modest, the consistent findings across multiple biological endpoints support further investigation of DHQ as a potential adjunct to radiotherapy. Further studies are warranted to validate these findings in more clinically relevant preclinical models.