Gabriel Ferreira Barbosa¹, Raquel Carvalho Montenegro¹, Emerson Lucena da Silva¹, Elmer Adilson Espino Zelaya¹, Laís Lacerda Brasil-Oliveira¹, Felipe Pantoja Mesquita¹, Pedro Filho Noronha de Souza¹

Colorectal cancer (CRC) affects the population worldwide, occupying the first place in terms of death and incidence. Synthetic peptides (SPs) emerged as alternative molecules due to their activity and low toxicity. Proteomic analysis of HCT-116 cells treated with PepGAT (GATIRAVNSR),a multiactive synthetic peptide designed from a plant protein called chitinase, revealed a decreased abundance of proteins involved in ROS metabolism and energetic metabolisms, cell cycle, DNA repair, migration, invasion, cancer aggressiveness, and proteins involved in resistance to 5-FU. PepGAT induced earlier ROS and apoptosis in HCT-116 cells, cell cycle arrest, and inhibited HCT-116 migration. PepGAT enhances the action of 5-FU against HCT-116 cells by dropping down 6-fold the 5-FU toward HCT-116 and reduces its toxicity for non-cancerous cells. These findings strongly suggest the multiple mechanisms of action displayed by PepGAT against CRC cells and its potential to either be studied alone or in combination with 5-FU to develop new studies against CRC and might develop new drugs against it.

Agradecimentos: This work was supported by the National Council for Scientific and Technological Development (CNPq) for a research grant to Felipe P. Mesquita (Process number: 421392/2023-1), for a research productivity grant to Raquel C. Montenegro (Process number: 305459/2019-8), Pedro F. N. Souza (Process number: 305003/2022-4), Raquel C. Montenegro also thanks Red Latinoamericana de Implementación y Validación de guias clínicas Farmacogenomicas (RELIVAF) for supporting this work. Pedro F. N. Souza also thanks the Cearense Foundation for the Support of Scientific and Technological Development (FUNCAP) for visiting the research grant (process no. PVS-0215 00099.01.00/23). We also thank the Office of Coordination for the Improvement of Higher Education Personnel (CAPES) for grants given to students. We are also grateful to the Multi-User Facility of the Drug Research and Development Center of the Federal University of Ceará for technical support with flow cytometry analysis.