Plant-derived Alkaloids as Emerging Therapeutic Agents for Colorectal Cancer: Molecular Mechanisms and Translational Perspectives.

INTRODUCTION: Plant-derived alkaloids have attracted growing attention in Colorectal Cancer (CRC) research because of their diverse biological activities and ability to regulate multiple oncogenic pathways. CRC remains a major cause of cancer-related mortality worldwide despite advances in diagnosis and therapy. METHODS: This review summarizes experimental and translational studies investigating the anticancer effects of plant-derived alkaloids in CRC, with emphasis on molecular mechanisms, cancer stem cell signaling, pharmacokinetic limitations, and recent patent-related developments. RESULTS: Experimental studies have demonstrated that several alkaloids, including berberine, matrine, evodiamine, and palmatine, inhibit CRC progression through the induction of apoptosis, suppression of proliferation, inhibition of epithelial-mesenchymal transition, and modulation of inflammatory and oxidative stress-associated pathways. These compounds also influence signaling pathways frequently dysregulated in CRC, including Wnt/β-catenin, PI3K/Akt/mTOR, MAPK, NF-κB, and JAK/STAT signaling. Recent patents have focused on alkaloid-based formulations, nanotechnology-driven delivery systems, and combination strategies designed to improve therapeutic efficacy and bioavailability. DISCUSSION: Although preclinical findings remain promising, most alkaloids investigated in CRC research continue to face limitations, including poor bioavailability, insufficient pharmacokinetic characterization, and limited clinical validation. CONCLUSION: Plant-derived alkaloids remain promising candidates for CRC therapy and chemoprevention. Further translational studies, pharmacological optimization, and clinically relevant investigations will be necessary to clarify their therapeutic applicability in CRC.