Targeting Metastasis with Snake Toxins: Molecular Mechanisms

Toxins (Basel). 2017 Nov 30;9(12):390. doi: 10.3390/toxins9120390.

Abstract

Metastasis involves the migration of cancer cells from a primary tumor to invade and establish secondary tumors in distant organs, and it is the main cause for cancer-related deaths. Currently, the conventional cytostatic drugs target the proliferation of malignant cells, being ineffective in metastatic disease. This highlights the need to find new anti-metastatic drugs. Toxins isolated from snake venoms are a natural source of potentially useful molecular scaffolds to obtain agents with anti-migratory and anti-invasive effects in cancer cells. While there is greater evidence concerning the mechanisms of cell death induction of several snake toxin classes on cancer cells; only a reduced number of toxin classes have been reported on (i.e., disintegrins/disintegrin-like proteins, C-type lectin-like proteins, C-type lectins, serinproteases, cardiotoxins, snake venom cystatins) as inhibitors of adhesion, migration, and invasion of cancer cells. Here, we discuss the anti-metastatic mechanisms of snake toxins, distinguishing three targets, which involve (1) inhibition of extracellular matrix components-dependent adhesion and migration, (2) inhibition of epithelial-mesenchymal transition, and (3) inhibition of migration by alterations in the actin/cytoskeleton network.

Keywords: anti-cancer agents; cancer cells; invasion; migrastatic drugs; snake venom.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion / drug effects
  • Cell Movement / drug effects
  • Disintegrins / isolation & purification
  • Disintegrins / pharmacology*
  • Epithelial-Mesenchymal Transition / drug effects
  • Humans
  • Neoplasm Metastasis / pathology*
  • Neoplasm Metastasis / prevention & control*
  • Snake Venoms / pharmacology*

Substances

  • Disintegrins
  • Snake Venoms