BIOINSPIRED SYNTHETIC ANTI-MICROBIAL PEPTIDE C IN VIVO EFFECT ON COLORECTAL CANCER CELL LINES IN ZEBRAFISH XENOGRAFT MODEL

Abstract

Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, and outcomes remain limited by drug resistance, toxicity, and tumor heterogeneity. Antimicrobial peptides (AMPs) have emerged as promising anticancer candidates due to their selective targeting of negatively charged cancer cell membranes and ability to induce apoptosis. In vitro, peptide C induced cytotoxicity, mitochondrial stress, and apoptosis in SW620 cells. Based on zebrafish toxicity profiling, defined concentrations of peptide C were used for xenograft experiments. In this study, the in vivo anticancer activity of an AMPs, peptide C, was investigated using zebrafish xenograft models of human CRC cell lines SW620 and COLO 205, together with complementary in vitro analyses. In SW620 xenografts, duct of Cuvier injections enabled systemic dissemination of cancer cells, while yolk sac injections allowed evaluation of localized cell expansion. Peptide C treatment did not consistently reduce whole-body fluorescence signals in the dissemination model but showed regional reductions in distal tail signals, suggesting possible effects on cancer cell migration. In the SW620 yolk xenograft model, peptide C significantly reduced fluorescence intensity and integrated density, indicating reduced CRC xenograft burden. COLO 205 cells incubated with peptide C were further analyzed using RT-qPCR and colony formation assays. Expression of the pro-apoptotic markers BAX and Caspase-3 increased, whereas proliferation markers MKI-67, CCND1, and PCNA showed minimal changes. Colony formation assays confirmed reduced clonogenic survival. In vivo COLO 205 yolk xenografts further demonstrated that peptide C significantly suppressed the expansion of GFP-positive cancer cells. Overall, these findings indicate that peptide C exerts cytotoxic and anti-proliferative effects on colorectal cancer cells, supporting its potential as a candidate anticancer peptide.

Date of Award	2026
Original language	American English
Awarding Institution	HBKU College of Health & Life Sciences