Antitumoral Potential of Snake Venom Phospholipases A2 and Synthetic Peptides

Abstract

Cancer, a disease that currently affects approximately 14 million people, is characterized by abnormal cell growth with altered replication capacity, which leads to the development of tumor masses without apoptotic control. Resistance to the drugs used in chemotherapy and their side effects stimulate scientific research seeking new therapies to combat this disease. Molecules from flora and fauna with cytotoxic activity against tumor cells have been studied for their potential to become a source of pharmaceutical agents. In this regard, snake venoms have a variety of proteins and peptides that have proven biotechnological potential. In several studies, antibacterial action and antitumor activity have been observed. One of the most widely studied venom components are phospholipases A2. Snake venom phospholipases A2 (svPLA2s) comprise a large class of molecules that catalyze the hydrolysis of the sn-2 position of phospholipids releasing fatty acids and lysophospholipids and are related to a broad spectrum of biotechnological activities. In addition to their specific cytotoxicity against some tumor cell lines, inhibitory activity of angiogenesis, adhesion and cell migration has been described. The antitumor activity of svPLA2s was observed both in vitro and in vivo, but little is known about the mechanism of action of these proteins in promoting this activity. In this review, the main structural and functional characteristics of svPLA2s are discussed, along with the mechanisms proposed, thus far, to explain their antitumor activity, targeting their potential use as a therapeutic alternative against cancer.

Identification of the Molecular Determinants of the Antibacterial Activity of LmutTX, a Lys49 Phospholipase A2 Homologue Isolated from Lachesis muta muta Snake Venom (Linnaeus, 1766)

“…Peptides derived from the C‐terminal region of PLA 2 homologues have been the focus of many studies to elucidate their contribution in the mechanism of myotoxic action of these proteins and/or in their use as possible antimicrobial and antitumour agents .…”

“…Differences were also found in MT-II (Lys49) from B. asper and LmTX-I (Asp49) from L. m. muta, where MT-II was cytotoxic at concentrations ≥30 lg/mL, while LmTX-I did not affect cell viability at any of the tested concentrations (70 to 270 lg/mL) [62,63]. The cytolytic action of Lys49 PLA 2 s is not restricted to muscle cells but also to other cell types, such as endothelial cells [64], macrophages [60], lymphocytes [65] and tumour cell lines [66,67].…”

“…Peptides derived from the C-terminal region of PLA 2 homologues have been the focus of many studies to elucidate their contribution in the mechanism of myotoxic action of these proteins and/or in their use as possible antimicrobial [20,23] and antitumour agents [66,67,70,74]. P aramo et al [20] showed that a C-terminal peptide, named p115-129 from B. asper's myotoxin II, had potent activity on strains of E. coli and S. aureus, via interaction with LPS and lipoteichoic acid molecules, respectively, with irreversible morphological changes in the membrane and cell death.…”

Nucleolin internalizesBothrops asperLys49 phospholipase A2forming cell surface amyloid-like assemblies

“…Second, the interaction of Mt-II with NCL may explain pharmacological properties of snake myotoxins. The preferential activity of these toxins against cancer cells (6,39,40) can be correlated to the fact that NCL is more abundant on the surface of these cells (16,41,42). Moreover, some snake PLA 2 s have been reported to have antiviral activity (43,44) and accordingly NCL is involved in internalization of many viruses (16,17).…”

“…Various pharmacological applications have been proposed to exploit the diverse functionalities of snake PLA 2 s, including antiviral and antitumoral activities. However, the basic mechanisms of these activities are not known (6)(7)(8).…”