Carely Arjona-Ruiz

Introduction: Colorectal cancer (CRC) is the third most common cancer worldwide and a leading cause of cancer-related mortality. Despite advances in surgery, chemotherapy, and targeted therapies, many CRC patients experience limited efficacy, toxicity, or drug resistance. Thus, complementary therapeutic strategies with an improved safety profile are needed. Plant-derived polyphenols emerge as promising candidates for CRC treatment. Methods: This review compiles in vitro, in vivo, and clinical evidence on the anticancer activity of polyphenols in CRC. Polyphenols, such as curcumin, resveratrol, quercetin, and flavonoids, are analyzed, with emphasis on molecular mechanisms and chemopreventive potential. Results: In vitro studies consistently demonstrate that these compounds exert anticancer effects by modulating multiple pathways, including PI3K/AKT/mTOR, Wnt/β-catenin, STAT3, and MAPK/ERK, promoting apoptosis and regulating oxidative stress and inflammation. In vivo studies indicate that curcumin, resveratrol, quercetin, epigallocatechin gallate (EGCG), genistein, luteolin, and fisetin significantly reduce tumor volume, polyp formation, and aberrant crypt foci (ACF). Curcumin has been extensively evaluated in trials, with some studies demonstrating reductions in ACF and improvements in inflammatory markers and quality of life, while others have demonstrated no significant clinical benefit. Discussion: Preclinical evidence supports the chemopreventive role of polyphenols. Preliminary clinical trials also suggest therapeutic potential for CRC prevention and treatment; however, large-scale, well-controlled clinical trials are required to confirm their safety and efficacy. Conclusion: Plant-derived polyphenols represent promising complementary strategies for CRC prevention and therapy. Future research should prioritize compounds with strong preclinical evidence, standardized formulations, optimized delivery strategies, and rigorously designed randomized trials to facilitate integration into clinical oncology practice.