Antitumoral activity of toxins from the endoparasitoid Cotesia flavipes (Hymenoptera: Braconidae)

• Grant number: 22/12499-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: October 01, 2023
• End date: September 30, 2025
• Field of knowledge: Health Sciences - Pharmacy - Toxicological Analysis
• Principal Investigator: Suely Vilela
• Grantee: Ciro Pedro Guidotti Pinto
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Arthropod venoms are composed by a wide range of compounds with a variety of pharmacological properties. These molecules have been studied and some successfully applied for anticancer therapy. Endoparasitoids use a pool of regulatory molecules in order to turn their hosts into a suitable environment for their offspring development. These regulatory molecules from parasitoids are still poorly explored for human health therapy, but some reports discuss their biotechnological potential. This project aims to explore toxins identified from teratocytes (embryonic-derived cells) and venom from the endoparasitoid C. flavipes for their antitumor properties in a cell-based screening system. By a robust proteotranscriptomic approach, we have uncovered the molecules from venom and teratocytes of the endoparasitoid Cotesia flavipes (Hymenoptera: Braconidae). Using this database, based on computational tool algorithm, six toxins were selected based on computational tools to be tested for their antitumor activity against the cell lines of hepatocellular carcinoma (HepG2), prostate carcinoma (DU-145), lung carcinoma (A549) breast adenocarcinoma (MDA-MB), acute promielocitic leukemia (HL-60) and acute monocitic leukemia (THP-1). The peptides will be produced by recombinant expression or solid phase synthesis. After purification, quality of molecules will be confirmed by mass spectrometry followed by an in silico investigation. The peptides will be evaluated for their influence on cell death, cellular migration and proliferation. We hope to find at least one peptide of C. flavipes with antitumor activity. In addition, we expect to introduce parasitoid molecules as strong candidates for pharmacological studies against antitumor cells, establishing a new branch on the research line of Prof. Suely Vilela. (AU)