A formulation combining resveratrol, derived from grapes and wine, and omega-3 fatty acids exerts anti-cancer activity by blocking neoangiogenesis, damaging the DNA of tumor cells, causing their death, and modulating the immune system

Abstract

Resveratrol, a key polyphenol from grapes and red wine, and omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), abundant in Mediterranean dietary patterns, provide complementary antioxidant, anti inflammatory, and anti tumor properties. Beyond their nutritional relevance, these bioactive food derived molecules represent a powerful and underexplored reservoir for developing novel cancer modulating strategies. We evaluated Resvega (RGA), a formulation combining resveratrol with EPA/DHA and clinically used in ocular diseases, as a diet inspired therapeutic candidate for colorectal cancer (CRC).  Anti cancer effects of RGA were examined in vivo, using murine CRC xenografts and the chicken embryo chorioallantoic membrane (CAM) model, with daily RGA administration (15 or 30 mg/kg), and in vitro, using human and murine CRC cell lines, immune competent 3D tumor spheroids, and human umbilical vein endothelial cells (HUVEC). Angiogenesis (VEGF A secretion, pseudotube formation), tumor growth, oxidative stress, DNA damage, apoptosis, ferroptosis, and immune modulation were evaluated with microscopy, immunoblotting, flow cytometry, and immunostaining. Toxicity was assessed in healthy human cells and in vivo.  RGA markedly inhibited angiogenesis by reducing VEGF A secretion of cancer cells and impairing HUVEC pseudotube formation, consistent with its known retinal anti angiogenic effects. Tumor growth was significantly reduced in CRC bearing mice and in CAM tumor model. Mechanistic analyses showed that RGA increased ROS production and induced DNA damage, leading to apoptosis and ferroptosis. In immune inclusive models, RGA modulated components of the tumor microenvironment relevant to anti tumor responses. No toxicity was detected in normal cells or animals.  These findings highlight that combining resveratrol with EPA/DHA, two emblematic bioactive compounds from Mediterranean diet, yields multi target anti tumor effects with an excellent safety profile. This work reinforces the concept that food derived molecules constitute a valuable and still largely untapped source for oncology innovation. RGA appears as a promising adjuvant candidate, warranting evaluation in combination with radiotherapy, chemotherapy, or immunotherapy to enhance efficacy without increasing toxicity.

References

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