Proteomic and peptidomic analysis of snake venom effect on cancer cell lines and mouse brain tissues

Abstract

Toxic substances and secretions of animals such as snakes, spiders and scorpions have been used in traditional medicine for the treatment of several diseases. Despite the inherent difficulty and high economic risk in the discovery and development of new drugs from natural products, the development and rapid advances of technologies such as mass spectrometry-based proteome analysis has allowed researchers to advance in a more focused characterization for the determination of key molecular targets in several diseases.There are several works in the literature describing the biochemical and physiological analyzes characterizing the snake venom effect on organs, tissues and cells, showing their toxic and cytotoxic effects as well as the induction of biochemical changes and imbalances. However, there are few or almost no studies characterizing the proteomic and peptidomic profiles of the effect of venom on organs, tissues, and cells aiming at the evaluating the affected molecular targets.Based on the hypothesis that low or sub-lethal doses of snake venom are capable to modulate protein expression in cells and cerebral tissues, this project aims to analyze the comparative proteomic and peptidomic profiles of different cancer cell lines (MCF7, MDA-MB231, A204, SK-MEL-28, HeLa, PANC-1, and Y1) and normal cells (HEK293, AsPC-1, HACAT, and Y1-RasKO) treated or not with Bothrops jararaca snake venom and cerebral tissues (cortex, cerebellum, hippocampus, hypothalamus and striatum) of mice treated or not with Crotalus durissus terrificus snake venom in order to correlate them with cellular morphological and histological data of the damage caused by the venom. These data may suggest new pharmacological targets and novel therapeutic approaches (i.e. targeting proteins initially affected by the venom) for the envenoming treatment by the studied venoms. (AU)