Mechanistically, the combination treatment upregulated p21, Bax, and caspase-3 expression while downregulating cyclin D1, CDK4, and Bcl-2, and profoundly suppressed the phosphorylation of STAT3, AKT, and ERK signaling pathways.<h4>Discussion</h4>These findings suggest that SMP-3 possesses distinct structural characteristics and significant anti-tumor efficacy, making it a promising medical food candidate for colorectal cancer treatment. Here, CDK4 is linked to colorectal cancer.