Highlights on the Role of Galectin-3 in Colorectal Cancer and the Preventive/Therapeutic Potential of Food-Derived Inhibitors

SIMPLE SUMMARY: Colorectal cancer (CRC) incidence is increasing worldwide and represents an important health problem.Therapy failure and progression to metastatic disease are major concerns. Among the factors involved in tumor growth, galectin-3 (Gal-3) plays an important role due to its ability to finetune a number of molecular players that act at different levels of cancer-related processes. A clear relationship between Gal-3 and CRC has been demonstrated. Several studies have, indeed, reported a pathogenetic role for this protein in intestinal inflammation and CRC onset/progression. Moreover, some plant-source food-derived bioactive compounds (mostly fibers and polyphenols) can contribute to the control of CRC onset/growth through their capacity to block Gal-3 activities. In this review, we summarize these studies, highlighting the influence of Gal-3 on CRC risk/progression, cancer cell spreading and patient prognosis, as well as the potential of natural food-derived Gal-3 inhibitors as promising candidates for CRC prevention and therapy. ABSTRACT: Colorectal cancer (CRC) is a leading cause of death worldwide. Despite advances in surgical and therapeutic management, tumor metastases and resistance to therapy still represent major hurdles. CRC risk is highly modifiable by lifestyle factors, including diet, which strongly influences both cancer incidence and related mortality. Galectin-3 (Gal-3) is a multifaceted protein involved in multiple pathophysiological pathways underlying chronic inflammation and cancer. Its versatility is given by the ability to participate in a wide range of tumor-promoting processes, including cell–cell/cell–matrix interactions, cell growth regulation and apoptosis, and the immunosuppressive tumor microenvironment. This review provides an updated summary of preclinical and observational human studies investigating the pathogenetic role of Gal-3 in intestinal inflammation and CRC, as well as the potential of Gal-3 activity inhibition by plant-source food-derived bioactive compounds to control CRC onset/growth. These studies highlight both direct and immuno-mediated effects of Gal-3 on tumor growth and invasiveness and its potential role as a CRC prognostic biomarker. Substantial evidence indicates natural food-derived Gal-3 inhibitors as promising candidates for CRC prevention and therapy. However, critical issues, such as their bioavailability and efficacy, in controlled human studies need to be addressed to translate research progress into clinical applications.