Introduction: Farnesiferol C (FFC) is a naturally occurring sesquiterpene coumarin extracted from Ferula species that has gained increasing attention because of its broad spectrum of pharmacological activities, including anti-inflammatory, antioxidant, and anticancer effects. Accumulating evidence indicates that FFC can modulate key molecular pathways involved in tumor cell proliferation and survival. Cervical cancer remains one of the most common malignancies among women worldwide, with a considerable mortality rate, especially in advanced stages of the disease. Although Ionizing radiation is used for treatment of cervical cancer, its clinical effectiveness is frequently reduced by inherent or acuquired resistance of cancer cells. The present study aimed to evaluate the effects of FFC, alone and in combination with radiotherapy, on the viability of HeLa cells, a commonly-used human cervical cancer cell line. Methods: The crystal powder of FFC (MW: 382.5g/mol) was dissolved in dimethyl sulfoxide (DMSO) to prepared the stock solution, and final concentrations of 25, 50 and 100 μM were prepared in DMEMHG supplemented with 10% FBS just before use. Accordingly, medium containing 0.3% DMSO was included in all the experiments as the solvent control. HeLa cells were seeded in 96-well plates and treated with FFC for 24, 72 and 120 h. For combined treatments with radiotherapy, cells were pretreated with 50 and 100 μM FFC for 48h, followed by exposure to IR at doses of 4, 6, and 8 Gy using the Elekta Compact™ linear accelerator (Crawley). After 72h recovery, cell viability was assessed by resazurin assay. Results: Treatment of cells with various concentrations of FFC reduced cell viability in a time- and dose-dependent manner. Regarding combined treatments with radiotherapy, pretreatment with 50 μM FFC followed by 4, 6 and 8 Gy irradiation reduced viability to 69.9%, 76.6% and 78.2%, respectively. Additionally, after 48 h pretreatment with 100 μM FFC followed by 4, 6 and 8 Gy irradiation, cell viability was reduced to 74.5%, 76.6% and 72.8%, respectively. Conclusion: Present findings revealed that FFC could be used in combination to improve effects of radiotherapy in cervical carcinoma cells. Neverthelss, further investigation using additional cancer cell lines and mechanistics analysis is required deeper delve into effects of FFC.

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