Molecular proteomic analysis of the effect of snake venom and its components on mouse tissues and cancer cell lines

• Grant number: 24/16166-0
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2025
• End date: July 31, 2028
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Leo Kei Iwai
• Grantee: Leo Kei Iwai
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Ana Claudia Oliveira Carreira Nishiyama ; Gisele Picolo ; Lilian de Jesus Oliveira ; Milton Yutaka Nishiyama Junior ; Rosangela Aparecida Wailemann Mansano

Abstract

Snake venom is a complex mixture of bioactive molecules with diverse biological activities, including anticancer properties. Despite the growing interest in its therapeutic applications, the molecular mechanisms underlying its cellular effects remain poorly understood. Advances in mass spectrometry-based proteomics have enabled the identification of key molecular targets, paving the way for new therapeutic approaches.This study represents a natural and strategic evolution of previous projects, such as FAPESP Regular 2017/17943-6 and the MSc 2017/06496-9, which have already demonstrated significant and high-impact results. The current proposal significantly expands the scope of these earlier works by incorporating new tissues, cell lines, and innovative methodologies, such as peptidomics and secretomics, which were not previously addressed. Additionally, the project benefits from an international collaboration with a researcher at the University of Georgia, in Atlanta, USA, who brings expertise in histopathological and pathological analyses, strengthening the multidisciplinary approach and enhancing the international impact of the research.This study is divided into two subprojects. In the first, we will use state-of-the-art mass spectrometry to investigate the systemic proteomic effects of envenomation by Crotalus durissus terrificus in different mouse tissues (kidney, lung, liver, muscle, and brain regions) and correlate them with histological analyses. In the second, we will analyze the proteomic, peptidomic, and secretomic profiles of the venoms of Bothrops jararaca and C. d. terrificus, as well as Crotoxin (CTX), in tumor cell lines (HeLa, SK-MEL-28, MCF7, MDA-MB-231, and Y1) and normal cell lines (MCF10A, HEK-293, HaCaT, and Y1-RasKO), correlating the findings with data on viability, morphology, cell cycle, proliferation, and migration.These approaches will enable a global mapping of the molecular effects of venom, facilitating the identification of new therapeutic targets. The results will have high scientific and technological impact, contributing to toxinology and oncology. The molecular characterization of venom will enable the discovery of new biomarkers and therapeutic strategies, including bioactive peptides with antitumor or anti-inflammatory potential and immune-modulating proteins with applications in autoimmune diseases. Furthermore, the findings may aid in the development of more effective antivenoms for envenomation by C. d. terrificus and B. jararaca, reducing their morbidity and mortality. (AU)