Cytotoxic effect of crotoxin on cancer cells and its antitumoral effects correlated to tumor microenvironment: A review

Author(s)

Almeida, Tamires Cunha ; Silva, Lorena de Morais Ribeiro ; de Oliveira, Ana Maria Boaventura ; Lopes, Flavia Souza Ribeiro ; Sant'Anna, Morena Brazil ; Picolo, Gisele

• Document type: Journal article
• Source: International Journal of Biological Macromolecules; v. 242, p. 8-pg., 2023-05-19.

Abstract

Cancer is the second leading cause of death worldwide, and despite the effort of standard treatments, the search for new tools against this disease is necessary. Importantly, it is known that the tumor microenvironment plays a crucial role in tumor initiation, progression, and response to therapies. Therefore, studies of potential drugs that act on these components are as critical as studies regarding antiproliferative substances. Through the years, studies of several natural products, including animal toxins, have been conducted to guide the development of medical compounds. In this review, we present the remarkable antitumor activities of crotoxin, a toxin from the rattlesnake Crotalus durissus terrificus, highlighting its effects on cancer cells and in the modulation of relevant elements in the tumor microenvironment as well as the clinical trials conducted with this compound. In sum-mary, crotoxin acts through several mechanisms of action, such as activation of apoptosis, induction of cell cycle arrest, inhibition of metastasis, and decrease of tumor growth, in different tumor types. Crotoxin also modulates tumor-associated fibroblasts, endothelial cells, and immune cells, which contribute to its antitumoral effects. In addition, preliminary clinical studies confirm the promising results of crotoxin and support its potential future use as an anticancer drug. (AU)

• FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
• Grantee: Hugo Aguirre Armelin
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 21/10344-5 - Identification of crotoxin-derived peptides with antitumor and immunomodulatory potential
• Grantee: Tamires Cunha Almeida
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/17109-1 - Identification of peptides derived from crotoxin with antitumor and immunomodulatory potential in a Cutaneous Melanoma model and in Experimental Autoimmune Encephalomyelitis model
• Grantee: Gisele Picolo
• Support Opportunities: Regular Research Grants