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

The phospholipase A(2) (PLA(2)) 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 PLA(2) 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 PLA(2) and LAAO contribute to an elevated oxidative stress due to their catalytic actions, for instance, the ability of PLA(2) 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 PLA(2) and LAAO in relationship to their catalytic mechanisms and the underlying mechanisms of cytotoxic actions.