Food-derived bioactive peptides as emerging therapeutic agents: Unlocking novel strategies for colorectal cancer treatment

Colorectal cancer (CRC) ranks as the third most common cancer globally, with 1.9 million newly diagnosed cases annually and nearly 935,000 deaths, posing substantial healthcare challenges worldwide. Food-derived bioactive peptides (FDBPs) are natural, non-toxic, and cost-effective compounds that exhibit significant potential in combating CRC. However, a comprehensive review summarizing FDBPs sources, peptide sequences, their anti-CRC effects, and underlying mechanisms is still lacking. Consequently, the present study discussed the CRC inhibitory effects and action mechanisms of FDBPs from different protein sources. We found that plant proteins, animal proteins, milk proteins, and microbial proteins are all ideal sources for producing peptides with high anti-CRC activity. Several peptides isolated from these proteins can promote apoptosis, inhibit metastasis, reduce invasion of CRC, and finally suppress tumor growth. Notably, low-molecular-weight FDBPs, particularly those below 1 kDa and rich in Asp, Gln, Lys, Gly, and Ser, exhibit better stability and stronger anti-CRC efficacy. The anti-CRC activity of FDBPs is associated with balancing the gut microbiota, activating the p38 MAPK pathway, and inhibiting the PI3K/AKT signaling pathway; however, the upstream and downstream regulatory mechanisms remain unclear. Additionally, we discovered that nanoparticle and glycopeptide modifications can enhance the activity and stability of anti-CRC peptides, enabling more precise delivery to cancer sites. Our review will be of interest for the design of natural anti-CRC drugs.