Resveratrol and capsaicin as safer radiosensitizers for colorectal cancer compared to 5-fluorouracil
Samuel Amintas, Charles Dupin, Marie‐Alix Derieppe, Isabelle Moranvillier, Isabelle Lamrissi, Corine Bourdié, Zoe Feurer, Benjamı́n Fernández, Tyty Heng-Pradère, François Moreau‐Gaudry, Aurélie Bedel, V. Vendrely, Sandrine Dabernat
Abstract
Standard rectal cancer treatment includes neoadjuvant radiotherapy sensitized by 5-fluorouracil (5-FU) chemotherapy. However, 5-FU increased chemoradiotherapy response rate comes with significant toxicity, especially in older, frail patients. The development of alternatives to chemotherapy enabling radiosensitization with limited systemic toxicity is therefore needed to improve patient management. Bioactive food components (BFCs) can exhibit chemo or radio-sensitizing properties against cancer cells. Moreover, the cytotoxic action of BFCs may be tumor-specific, with reduced impact on healthy cells. We hypothesized that BFCs, in particular resveratrol and capsaicin, alone or in association, could lead to specific radio-sensitization of colorectal tumors while offering reduced toxicity compared to 5-FU. Colorectal tumor and non-tumor cell lines were treated with resveratrol, capsaicin, or 5-FU, alone or in combination, then irradiated; survival, cell cycle, and apoptosis were analyzed. RAGγ2C−/− mice with xenografts received oral resveratrol, resveratrol + capsaicin, or 5-FU, followed by radiotherapy, with tumor growth and systemic toxicity evaluated. Resveratrol alone or in association with capsaicin radio-potentiates colorectal tumor cells in vitro , impacting both cell cycle and apoptosis. In a preclinical mouse model, the oral administration of resveratrol and capsaicin, but not resveratrol alone, allowed the radio-sensitization of subcutaneous colorectal tumors with similar efficiency to 5-FU. Moreover, the global as well as the hematological toxicity of the BFC association was lower than those of 5-FU. This work establishes BFCs as effective enhancers of radiotherapy, offering a safer alternative to traditional radiosensitization with chemotherapy. • Resveratrol and capsaicin, or resveratrol alone, enhance radiotherapy in vitro, equaling or surpassing 5-FU efficacy. • Resveratrol and capsaicin increase radiotherapy efficacy like 5-FU in a preclinical xenografted mouse model. • Resveratrol alone is not sufficient to potentiate radiotherapy in a preclinical model of colorectal cancer. • Resveratrol and capsaïcin display reduced systemic side effects compared to 5-FU. • Resveratrol and capsaicin association could offer a safer alternative to toxic conventional 5-FU-based radiosensitization chemotherapy.