Introduction: Cervical carcinoma represents the fourth leading cause of cancer-related mortality among women worldwide. Radiotherapy is among therapeutic modalities for cervical carcinoma, either as a curative treatment alone or in combination with surgery and chemotherapy. However, the effectiveness of radiotherapy is limited as tumor cells develop radioresistance over time, contributing to recurrence and treatment failure. Therefore, improving tumor radiosensitivity while minimizing damage to surrounding normal tissues is an important issue. Natural compounds have become a focus of interest as potential radiosensitizers due to their biological activity and relatively low toxicity. Ferula species are well known in traditional medicine for their pharmacological properties, including antioxidant and anticancer effects. Auraptene, a sesquiterpene coumarin isolated from Ferula plants, has demonstrated cytotoxic and pro-apoptotic activities in various cancer models. In this study, we aimed to investigate the potential of auraptene as a radiosensitizer in human cervical carcinoma cells. Methods: To determine the effects of auraptene in combination with radiotherapy, HeLa cells (a human cervical carcinoma cell line) were pretreated with 50 µM and 100 µM auraptene for 48 h. Then, cells were exposed to 4, 6, and 8 Gy X-ray, and after 72 h recovery, cell viability was determined by alamarBlue assay. Briefly, 10% v/v alamarBlue solution was added to cells, and after 3 h incubation, absorbance was measured at 600 nm. Finally, viability was calculated and morphological alterations of cells were recorded. Results: Viability assessment indicated that 95.5% and 80.7% of HeLa cells were alive upon single use of 50 µM and 100 µM auraptene for 120 h, respectively. However, 82.8% and 66.4% of cells were viable after pretreatment with 50 µM and 100 µM auraptene and exposure to 4 Gy IR, respectively. Additionally, cell viability was calculated as 88.1% and 67.7% upon pretreatment with 50 µM and 100 µM auraptene and exposure to 6 Gy IR, respectively. Regarding the highest dose of radiation, pretreatment with 50 µM and 100 µM auraptene and exposure to 8 Gy IR reduced cell viability to 81.2% and 61.6%, respectively. Conclusion: Obtained findings demonstrated that pretreatment of HeLa cells with 100 µM auraptene increases their sensitivity to radiotherapy. Cervical carcinoma cells exhibit radioresistance through several mechanisms, including enhanced DNA repair capacity, dysregulated apoptotic signaling, altered redox homeostasis, and elevated antioxidant defenses. Auraptene may attenuate this resistance by modulating one or more of these pathways. However, further studies are needed to elucidate its precise radiosensitizing potential.

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