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Identification of peptides derived from crotoxin with antitumor and immunomodulatory potential in a cutaneous melanoma model and in experimental autoimmune encephalomyelitis model

Grant number: 19/17109-1
Support type:Regular Research Grants
Duration: July 01, 2020 - June 30, 2022
Field of knowledge:Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
Principal researcher:Gisele Picolo
Grantee:Gisele Picolo
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

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. Therefore, this study aims to evaluate antitumor and immunomodulatory activities of crotoxin fragments in a cutaneous and EAE model melanoma model, through in vivo and in vitro assays, in order to contribute to understand of the actions triggered by CTX and to reveal new therapeutic agents for the treatment of cutaneous melanoma and MS. (AU)