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

Int J Biol Macromol. 2023 Jul 1;242(Pt 2):124892. doi: 10.1016/j.ijbiomac.2023.124892. Epub 2023 May 15.

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 summary, 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.

Keywords: Antitumoral effects; Crotalus durissus terrificus; Crotoxin; Drug discovery; Tumor microenvironment; cancer.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents* / pharmacology
  • Crotalid Venoms* / toxicity
  • Crotoxin* / pharmacology
  • Endothelial Cells / metabolism
  • Neoplasms* / drug therapy
  • Tumor Microenvironment

Substances

  • Crotoxin
  • Crotalid Venoms
  • Antineoplastic Agents