Analysis of the mechanisms of action of a peptide synthesized from a spider venom prototype in human glioma cell lines

• Grant number: 23/14743-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): August 01, 2024
• Effective date (End): July 31, 2026
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Catarina Raposo Dias Carneiro
• Grantee: Natália Barreto dos Santos
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

I. Overview: Gliomas account for approximately 80% of brain tumors malignant primaries in adults. Mainly due to its invasiveness, characterized byhigh ability to migrate and invade healthy brain substance, these are tumors that are difficult totreatment, being responsible for the majority of deaths associated with brain cancer. He wasrecently demonstrated by our research group that the venom of the Phoneutria spider nigriventer (PnV) has antitumor effects in vitro and in vivo models, impairing the migration and proliferation of human glioma cell lines. After screening thecrude venom, the LW-11 peptide was identified and selected as the main molecule capable to affect the migration of gliomas; the peptide was characterized and synthesized.II. Strategy: This project aims to: 1. Identify changes in proteins in signaling that regulate cell migration, by global proteomics, in glioma cell lines human treated with LW-11; 2. Assess total RNA in glioma cells, identifying targetsof the peptide, through RNA-seq; 3. Validate targets identified by proteomics and RNA-seq,using the CRISPR/Cas9 gene editing technique; 4. Confirm the mechanisms of action of the peptide in different high-grade glioma lines previously established by group a from patient tumors. Objectives 2 and 3 will be achieved during an internship abroad (details: BEPE plan).III. Integration and feasibility: This proposal includes the expertise of the supervisor and thepostdoctoral student in the selection and mechanistic analysis of potential drugs to combat tumors. Learning RNA-seq and CRISPR/Cas9 techniques during an internship abroad will enablethe pioneering implementation in the LATERA laboratory; the methods are developed by a fewresearchers in Brazil and could represent a major advance in the group for detecting mechanisms of action and development of treatments for cancer. Furthermore, the strategy will consolidate the partnership with the Sobreira Lab group, from the University of California (UCLA), which can contribute to other group work.IV. Development and social impact: Treating brain tumors is challenging. Some Glioma subtypes, such as glioblastoma, are highly invasive and, even after treatment, patients have a median survival of less than 18 months. The study has the perspective main contribution to the development of new therapies against gliomas, taking into account the social demand for cancer treatment.