Nutritional approach as a suitable intervention to prevent the GI tract pre-carcinogenic inflammatory status induced by multipollutant exposure

Abstract:

Colorectal cancer (CRC) was the second leading cause of cancer death and the third most commonly diagnosed cancer in 2022 with over 1.9 million new cases and approximately 904,000 deaths. CRC risk is determined by non-modifiable biological factors and modifiable lifestyle factors, including diet and pollution exposure. These factors influence the immune system and cellular homeostasis, promoting inflammation and redox imbalance, that favor tumor initiation and progression. In this context, preventive dietary strategies are gaining increasing attention. Walnuts are of scientific interest because their bioactive compounds (phytosterols, tocopherols, carotenoids) offer anti-inflammatory, antioxidant, and anti-cancer benefits. Therefore, this project aims to test whether walnut consumption can have preventive effects against CRC. We will evaluate how walnut-derived bioactive compounds counteract inflammation-driven tumorigenesis induced by multipollution exposure (MPE, i.e. microplastics and airborne particulate matter). After simulated in vitro digestion, the potential of walnut bioactives to modify major molecular mechanisms induced by MPE and involved in CRC development will be assessed in CaCo2 (human colorectal cancer cells) and CCD-841-CoN (non-tumorigenic colon epithelial cells). Our approach will involve monolayer cell cultures and organoids, as they more accurately mimic the in vivo microenvironment. We will perform cell proliferation and viability (CCK-8, MTT, and BrdU assays) as well as migration and invasion (wound healing and Boyden chamber assays, colony formation), and cytotoxicity assays. Furthermore, expression of proteins and genes involved in cell cycle progression, and inflammasomes activation will be evaluated by Western blot, qPCR, and immunofluorescence. We will elucidate how digested walnut bioactives modulate inflammatory pathways and tumorigenic behaviors at the cellular level, providing insights into their potential for CRC prevention.