School of Science, Monash University Malaysia, 47500 Bandar Sunway, Malaysia.
Biochem Soc Trans. 2020 Apr 29;48(2):719-731. doi: 10.1042/BST20200110.
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.
磷脂酶 A2（PLA2）和 l-氨基酸氧化酶（LAAO）是大多数蛇毒中发现的两种主要酶。这些酶的结构和功能已因其药理学活性而得到表征。来自不同毒液的 PLA2 和 LAAO 通过诱导细胞凋亡、细胞周期停滞和抑制增殖，对癌细胞表现出相当大的细胞毒性作用。这些酶在癌细胞中的细胞毒性作用比正常细胞更为明显，因此它们可以作为化疗药物的潜在来源。有人提出，由于 PLA2 和 LAAO 的催化作用，会导致氧化应激升高，例如，PLA2 在脂肪分解过程中产生活性氧物质的能力，以及 LAAO 催化活性产生 H2O2 的能力，这会导致细胞死亡。尽管如此，与接触这些酶毒素相关的细胞死亡信号通路尚未完全阐明。在这篇综述中，我们将讨论 PLA2 和 LAAO 的细胞毒性作用与其催化机制和细胞毒性作用的潜在机制之间的关系。
