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

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.

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.

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.

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.

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.