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

• Grant number: 17/17943-6
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2018
• End date: October 31, 2020
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• 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: Edmilson Ozorio dos Santos ; Marcelo da Silva Reis ; Matheus Henrique dos Santos Dias ; Milton Yutaka Nishiyama Junior
• Associated scholarship(s): 19/21075-5 - Proteomic analysis of Crotalus durissus terrificus snake venom effect on different mouse brain tissues, BP.TT; 19/19047-3 - Proteomic Characterization of Crotalus durissus terrificus snake venom on tumor cell lines, BP.TT; 18/25087-5 - Proteomic analysis of Swiss mice tissues under the effect of Crotalus durissus terrificus snake venom, BP.TT; 18/16553-2 - Proteomic and peptidomic analysis of snake venom effect on cancer cell lines and mouse brain tissues, BP.TT

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)

Scientific publications

(8)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FIGUEIREDO, D. A. L.; SANTOS, W. S.; MONTONI, FABIO; IWAI, LEO KEI; SILVA JUNIOR, I, P.. Toposome: Source of antimicrobial molecules in the gonads of the sea urchin Lytechinus variegatus (Lamarck, 1816). FISH & SHELLFISH IMMUNOLOGY, v. 109, p. 51-61, FEB 2021. (17/17943-6, 16/04000-3)

NAVARRO, MARINA V.; CHAVES, ALISON F. A.; CASTILHO, DANIELE G.; CASULA, ISIS; CALADO, JULIANA C. P.; CONCEICAO, PALLOMA M.; IWAI, LEO K.; DE CASTRO, BEATRIZ F.; BATISTA, WAGNER L.. Effect of Nitrosative Stress on theS-Nitroso-Proteome ofParacoccidioides brasiliensis. FRONTIERS IN MICROBIOLOGY, v. 11, JUN 4 2020. (17/04592-0, 13/07467-1, 16/04000-3, 15/09654-9, 17/17943-6)

NOVAES, TATIANE FERNANDES; JORDAO, MAISA CAMILLO; BONACINA, CARLOS FELIPE; VERONEZI, ANDRE OSWALDO; RODRIGUES DE ARAUJO, CARLOS ARIEL; OLEGARIO, ISABEL CRISTINA; DE OLIVEIRA, DANIELE BOINA; USHAKOVA, VERANIKA; BIRBRAIR, ALEXANDER; PALACIO, DANIELLE DA COSTA; et al. COVID-19 pandemic impact on dentists in Latin America's epicenter: SAo-Paulo, Brazil. PLoS One, v. 16, n. 8, AUG 26 2021. (13/07467-1, 17/17943-6)

MONTONI, FABIO; ANDREOTTI, DIANA ZUKAS; DOS SANTOS EICHLER, ROSANGELA APARECIDA; SANTOS, WELLINGTON DA SILVA; KISAKI, CAROLINA YUKIKO; SUEHIRO ARCOS, STEPHANIE SANTOS; LIMA, ISMAEL FEITOSA; MALTAURO SOARES, MAGNA APARECIDA; NISHIYAMA-JR, MILTON YUTAKA; NAVA-RODRIGUES, DANIEL; et al. The impact of rattlesnake venom on mice cerebellum proteomics points to synaptic inhibition and tissue damage. JOURNAL OF PROTEOMICS, v. 221, JUN 15 2020. (17/17943-6, 13/07467-1, 16/04000-3, 15/50040-4, 17/06496-9)

SANCHEZ-ROJAS, TITO; ESPINOZA-CULUPU, ABRAHAM; RAMIREZ, PABLO; IWAI, LEO KEI; MONTONI, FABIO; MACEDO-PRADA, DIEGO; SULCA-LOPEZ, MARCOS; DURAN, YERSON; FARFAN-LOPEZ, MARIELLA; HERENCIA, JENNIFER. Proteomic Study of Response to Copper, Cadmium, and Chrome Ion Stress in Yarrowia lipolytica Strains Isolated from Andean Mine Tailings in Peru. MICROORGANISMS, v. 10, n. 10, p. 22-pg., 2022-10-01. (17/17943-6, 13/07467-1)

MOREIRA, RAFAEL J.; CASTRO, ERIQUE; OLIVEIRA, TIAGO E.; BELCHIOR, THIAGO; PEIXOTO, ALBERT S.; CHAVES-FILHO, ADRIANO B.; MORENO, MAYARA F.; LIMA, JANAYNA D.; YOSHINAGA, MARCOS; MIYAMOTO, SAYURI; et al. Lipoatrophy-Associated Insulin Resistance and Hepatic Steatosis are Attenuated by Intake of Diet Rich in Omega 3 Fatty Acids. MOLECULAR NUTRITION & FOOD RESEARCH, v. 64, n. 7, FEB 2020. (13/07467-1, 16/04000-3, 17/17943-6, 15/19530-5, 14/06863-3, 18/15549-1, 13/07937-8)

KISAKI, CAROLINA YUKIKO; ARCOS, STEPHANIE SANTOS SUEHIRO; MONTONI, FABIO; DA SILVA SANTOS, WELLINGTON; CALACINA, HAMIDA MACEDO; LIMA, ISMAEL FEITOSA; CAJADO-CARVALHO, DANIELA; FERRO, EMER SUAVINHO; NISHIYAMA-JR, MILTON YUTAKA; IWAI, LEO KEI. Bothrops Jararaca Snake Venom Modulates Key Cancer-Related Proteins in Breast Tumor Cell Lines. TOXINS, v. 13, n. 8, AUG 2021. (17/06496-9, 13/07467-1, 16/04000-3, 17/17943-6)

SANTOS, W. S.; MONTONI, FABIO; EICHLER, R. A. S.; SUEHIRO ARCOS, STEPHANIE SANTOS; ANDREOTTI, DIANA ZUKAS; KISAKI, CAROLINA YUKIKO; EVANGELISTA, KIMBERLY BORGES; CALACINA, HAMIDA MACEDO; LIMA, ISMAEL FEITOSA; MALTAURO SOARES, MAGNA APARECIDA; et al. Proteomic analysis reveals rattlesnake venom modulation of proteins associated with cardiac tissue damage in mouse hearts. JOURNAL OF PROTEOMICS, v. 258, p. 12-pg., 2022-04-30. (17/06496-9, 13/07467-1, 17/17943-6, 16/04000-3)