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.
Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with radioresistance and limited treatment options. Titanium dioxide nanoparticles (TiO2-NPs) have attracted attention as potential radiosensitizers because they can enhance radiation-induced oxidative stress. This study evaluated the radiosensitizing effects of BSA-adsorbed TiO2-NPs in MDA-MB-231 TNBC cells exposed to clinically relevant 6 MV X-ray irradiation. FITC-based cellular association, as an indicator of potential nanoparticle uptake, metabolic activity, clonogenic survival, sensitizer enhancement ratio (SER), reactive oxygen species (ROS), γ-H2AX positivity, and apoptosis were assessed. Flow cytometric analysis showed that approximately 55% of cells were FITC-positive after 24 h of exposure, while approximately 90% metabolic activity was maintained at the selected concentration (25 µg/mL). Combined treatment significantly reduced the surviving fraction from 0.81 to 0.37 after 2 Gy irradiation and yielded SER values of 1.21 and 1.59 at SER10 and SER37, respectively. In addition, combined treatment produced the greatest increases in intracellular ROS generation, γ-H2AX positivity, and apoptosis compared with either treatment alone. These findings indicate that BSA-adsorbed TiO2-NPs increase the radiosensitivity of TNBC cells under clinically relevant megavoltage irradiation and support their further evaluation as potential radiosensitizers for breast cancer radiotherapy.