Identification of crotoxin-derived peptides with antitumor and immunomodulatory potential

• Grant number: 21/10344-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2021
• End date: December 10, 2023
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Gisele Picolo
• Grantee: Tamires Cunha Almeida
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling, AP.CEPID

Abstract

Crotoxin (CTX) is a neurotoxin isolated from Crotalus durissus terrificus snake venom that exhibits anti-inflammatory, immunomodulatory and antitumor activities. In this sense, many studies have demonstrated that CTX exerts a striking antitumor effect in several types of tumor, such as cutaneous melanoma, a disease without cure. On the other hand, recently, our group has demonstrated that CTX is able to alter the developmental course and disease severity in Experimental Autoimmune Encephalomyelitis (EAE) model, an animal model of Multiple Sclerosis (MS), a neurodegenerative disease without cure, which affects thousands of people and represents a great personal and socioeconomic burden. It is worth to mention that drugs available for the treatment of MS and cutaneous melanoma are of low efficacy and induce many adverse effects, justifying the search for new molecules with more efficiency and free of side effects. Despite CTX intriguing actions on melanoma cells and in the EAE model, its use is limited by its toxicity, and the toxin fragment responsible for these effects remains unknown. In this regard, it is known that CTX is a non-patentable natural product and due to its complex structure its recombinant synthesis or production is impracticable, turning essential the identification of the toxin fragment responsible for these effects. Preliminary studies by our group demonstrated that crotoxin, both in its native and detoxified form, has an antitumor effect in SK-MEL-28 human cells melanoma line. Therefore, this study aims to evaluate the antitumor and immunomodulatory activities of these compounds in a model of cutaneous melanoma and Experimental Autoimmune Encephalomyelitis (EAE) through in vitro and in vivo assays, as well as to identify possible fragments responsible for these effects, in order to contribute to the understanding of the actions triggered by CTX and to highlight new therapeutic agents for the treatment of Cutaneous Melanoma and Multiple Sclerosis. (AU)

Scientific publications

(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)

ALMEIDA, TAMIRES CUNHA; SILVA, LORENA DE MORAIS RIBEIRO; DE OLIVEIRA, ANA MARIA BOAVENTURA; LOPES, FLAVIA SOUZA RIBEIRO; SANT'ANNA, MORENA BRAZIL; PICOLO, GISELE. Cytotoxic effect of crotoxin on cancer cells and its antitumoral effects correlated to tumor microenvironment: A review. International Journal of Biological Macromolecules, v. 242, p. 8-pg., 2023-05-19. (13/07467-1, 21/10344-5, 19/17109-1)