Cytotoxicity of snake venom enzymatic toxins: phospholipase A2 and l-amino acid oxidase

Biochem Soc Trans. 2020 Apr 29;48(2):719-731. doi: 10.1042/BST20200110.

Abstract

The phospholipase A2 (PLA2) and l-amino acid oxidase (LAAO) are two major enzymes found in the venoms from most snake species. These enzymes have been structurally and functionally characterised for their pharmacological activities. Both PLA2 and LAAO from different venoms demonstrate considerable cytotoxic effects on cancer cells via induction of apoptosis, cell cycle arrest and suppression of proliferation. These enzymes produce more pronounced cytotoxic effects in cancer cells than normal cells, thus they can be potential sources as chemotherapeutic agents. It is proposed that PLA2 and LAAO contribute to an elevated oxidative stress due to their catalytic actions, for instance, the ability of PLA2 to produce reactive oxygen species during lipolysis and formation of H2O2 from LAAO catalytic activity which consequently lead to cell death. Nonetheless, the cell-death signalling pathways associated with exposure to these enzymatic toxins are not fully elucidated yet. Here in this review, we will discuss the cytotoxic effects of PLA2 and LAAO in relationship to their catalytic mechanisms and the underlying mechanisms of cytotoxic actions.

Keywords: l-amino acid oxidase; apoptosis; cancer; cytotoxicity; phospholipase A2; reactive oxygen species.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis*
  • Cell Cycle
  • Cell Death / drug effects
  • Cell Proliferation
  • Cell Survival / drug effects
  • Drug Screening Assays, Antitumor
  • Humans
  • L-Amino Acid Oxidase / metabolism*
  • Ligands
  • Lipolysis
  • Neoplasms / drug therapy
  • Oxidative Stress
  • Phospholipases A2 / metabolism*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • Snake Venoms / enzymology*

Substances

  • Antineoplastic Agents
  • Ligands
  • Reactive Oxygen Species
  • Snake Venoms
  • L-Amino Acid Oxidase
  • Phospholipases A2