Evaluation of resveratrol radiomodifying potential for radiotherapy treatment

Abstract

Radiotherapy is widely used for cancer treatment. However, its adverse effects that may develop during the course of treatment have forced to search agents to protect biological systems against the deleterious effects of radiation. Resveratrol (3,4,5-trihydroxy-trans-stilbene; RSV) is a natural polyphenol currently promoted for its beneficial pleiotropic effects on health, which has been shown to exhibit antioxidant properties while inhibiting the growth of tumor cells. In radioresistant tumors, RSV could contribute to reduce recurrence and treatment failure. We evaluated the radiomodulatory and genotoxic effects of RSV in CHO-k1 and A549 cell lines and in peripheral human blood lymphocytes through both conventional and hypofractionated protocols, due to the widespread use of hypofractionation in recent years. RSV genotoxic and cytotoxic action was assessed at 15 and 60 μM concentrations with the comet and the MTT assay and in cell proliferation experiments. Our results show that RSV administration to tumor cells at a dose of 60 μM exerted a genotoxic effect and that this concentration also had the capacity of modulating the cytomolecular damage induced by 4 and 16 Gy. These doses are delivered in conventional and hypofractionated radiotherapy, respectively. In both treatments, a radiosensitizing effect was evidenced by the decrease in cell viability that was exacerbated over time. These effects were not found in peripheral blood, suggesting that RSV had a dual response. Although the results obtained in CHO-k1 transformed cells corroborated the genotoxic effect of the 60 μM dose of RSV observed in the tumor system, they also showed a radio-protective effect at the lowest dose (15 μM). While more studies are necessary, our results together with the good systemic tolerance of RSV and the lack of toxicity position the compound as a potential candidate for the prevention and treatment of cancer as well as for the optimization of the radiotherapeutic ratio.