Amintas Samuel, Dupin Charles, Derieppe Marie-Alix, Moranvillier Isabelle, Lamrissi Isabelle, Bourdié Corine, Feurer Zoe, Fernandez Benjamin, Heng-Pradère Tyty, Moreau-Gaudry François, Bedel Aurélie, Vendrely Véronique, Dabernat Sandrine
University of Bordeaux, Bordeaux, France; INSERM U1312, Bordeaux Institute of Oncology - BRIC, BioGo Team, Bordeaux, France; Tumor Biology and Tumor Bank Department, Bordeaux University Hospital, Bordeaux, France.
University of Bordeaux, Bordeaux, France; INSERM U1312, Bordeaux Institute of Oncology - BRIC, BioGo Team, Bordeaux, France; Radiotherapy Department, Bordeaux University Hospital, Bordeaux, France.
Biomed Pharmacother. 2025 Feb;183:117799. doi: 10.1016/j.biopha.2024.117799. Epub 2025 Jan 3.
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.
标准的直肠癌治疗包括新辅助放疗，并通过5-氟尿嘧啶（5-FU）化疗进行增敏。然而，5-FU提高放化疗反应率的同时伴有显著毒性，尤其是在老年体弱患者中。因此，需要开发能够在全身毒性有限的情况下实现放射增敏的化疗替代方案，以改善患者管理。生物活性食品成分（BFCs）可对癌细胞表现出化学或放射增敏特性。此外，BFCs的细胞毒性作用可能具有肿瘤特异性，对健康细胞的影响较小。我们假设BFCs，特别是白藜芦醇和辣椒素，单独使用或联合使用，可导致结直肠肿瘤特异性放射增敏，同时与5-FU相比毒性降低。
用白藜芦醇、辣椒素或5-FU单独或联合处理结直肠肿瘤和非肿瘤细胞系，然后进行照射；分析细胞存活率、细胞周期和凋亡情况。对移植了肿瘤的RAGγ2C-/-小鼠口服白藜芦醇、白藜芦醇+辣椒素或5-FU，随后进行放疗，评估肿瘤生长和全身毒性。
白藜芦醇单独或与辣椒素联合在体外对结直肠肿瘤细胞具有放射增敏作用，影响细胞周期和凋亡。在临床前小鼠模型中，口服白藜芦醇和辣椒素（而非单独口服白藜芦醇）可使皮下结直肠肿瘤放射增敏，效率与5-FU相似。此外，BFC联合用药的总体毒性和血液学毒性低于5-FU。
本研究证实BFCs是有效的放疗增强剂，为传统化疗放射增敏提供了更安全的替代方案。
