Researchers tested a short piece of the antimicrobial peptide LL‑37, called KR‑12, and a few chemically tweaked versions, to see if they could kill colon cancer cells and reduce tumors in mice. In lab dishes the peptides were more toxic to cancer cells than to normal colon cells, and when given rectally to mice with chemically induced colon cancer they lowered tumor counts and inflammation. However, the effective doses were relatively high and the work is still at the early animal‑study stage, so it isn’t ready for personal use yet.

Colorectal cancer (CRC) remains a major global health challenge, with increasing incidence, particularly among individuals under 50 years of age. Cathelicidin LL-37, a multifunctional antimicrobial peptide, has shown promise in cancer treatment, particularly for its anti-inflammatory effects. Using in vitro and in vivo models, we investigated the anticancer potential of KR-12 amide, the shortest active fragment of LL-37, and its short-chain fatty acid (SCFA)-modified derivatives (acetyl-, propionyl-, and butyryl-KR-12-NH₂). Peptides were synthesized by Fmoc solid-phase synthesis and purified by RP-HPLC. Their cytotoxicity was assessed in colon cancer HT-29 and normal colon epithelial CCD 841 CoN cell lines using MTT viability assays. In vivo efficacy was evaluated in a mouse (male Balb/C mice) azoxymethane/dextran sodium sulfate (AOM/DSS) model of colitis-associated colorectal cancer (CACRC). Tumor burden was quantified by macroscopic and histological scoring, while inflammation was assessed through myeloperoxidase activity, ELISA-based cytokine profiling (IL-1β, IL-6, TNF-α), and microscopic evaluation of colon architecture. For all tested compounds, except KR-12-NH₂ modified with butyric acid, the concentrations needed for 50% growth inhibition were lower for colon cancer cell line HT-29 than for healthy colon epithelial cells CCD 841 CoN. The IC₅₀ values for KR-12 amide and propionyl-KR-12-NH₂ against HT-29 cells were 236.7 µM and 309.0 µM, respectively, compared with 347.3 µM and 422.1 µM for CCD 841 CoN cells. In the AOM/DSS-induced murine model, rectal administration of KR-12-NH₂ and propionyl-KR-12-NH₂ significantly reduced total tumor number compared with AOM/DSS-only animals (p = 0.02 and p = 0.03, respectively), accompanied by lower macroscopic (both p < 0.001) and microscopic disease scores (p = 0.005 and p = 0.01). Both compounds also significantly decreased proinflammatory cytokines: rectal KR-12-NH₂ lowered IL-6 levels (p = 0.05), while rectal propionyl-KR-12-NH₂ reduced IL-6 (p = 0.02) and TNF-α (p = 0.01). These findings provide a foundation for further investigation of cathelicidin derivatives in colorectal cancer therapy.