蛇毒是蛋白质和多肽的复杂混合物，是了解新药开发的生理过程的潜在分子工具的宝贵来源。在这项研究中，从阿根廷东北部的Bothrops diporus的毒液中分离出两种主要的PLA2，名为PLA2-I (Asp49)和PLA2-II (Lys49)，它们对LM3小鼠乳腺肿瘤细胞显示出细胞毒性作用，与PLA2-II类似与PLA2-I相比表现出更强的效果。在亚细胞毒性水平下，两种 PLA2 均抑制这些腺癌细胞的粘附、迁移和侵袭。此外，这些毒素阻碍内皮细胞的肾小管生成，暗示其在抑制肿瘤血管生成中具有潜在作用。对于无催化活性的毒素，所有这些抑制作用更为明显。此外，计算机研究强烈表明，这种类似 PLA2-II 的肌毒素可以有效阻断纤连蛋白与整合素受体的结合，在与 αVβ3 整合素相互作用方面比 PLA2-I 具有双重优势。总之，本研究首次报告，结合体外和计算机方法，对两种亚型（Asp49 PLA2-I 和 Lys49 PLA2-II 样）的抗转移和抗血管生成潜在作用进行了比较分析，这两种亚型均是分离的来自 Bothrops diporus 毒液。版权所有 © 2024。由 Elsevier B.V. 出版

Snake venoms are a complex mixture of proteins and polypeptides that represent a valuable source of potential molecular tools for understanding physiological processes for the development of new drugs. In this study two major PLA2s, named PLA2-I (Asp49) and PLA2-II (Lys49), isolated from the venom of Bothrops diporus from Northeastern Argentina, have shown cytotoxic effects on LM3 murine mammary tumor cells, with PLA2-II-like exhibiting a stronger effect compared to PLA2-I. At sub-cytotoxic levels, both PLA2s inhibited adhesion, migration, and invasion of these adenocarcinoma cells. Moreover, these toxins hindered tubulogenesis in endothelial cells, implicating a potential role in inhibiting tumor angiogenesis. All these inhibitory effects were more pronounced for the catalytically-inactive toxin. Additionally, in silico studies strongly suggest that this PLA2-II-like myotoxin could effectively block fibronectin binding to the integrin receptor, offering a dual advantage over PLA2-I in interacting with the αVβ3 integrin. In conclusion, this study reports for the first time, integrating both in vitro and in silico approaches, a comparative analysis of the antimetastatic and antiangiogenic potential effects of two isoforms, an Asp49 PLA2-I and a Lys49 PLA2-II-like, both isolated from Bothrops diporus venom.Copyright © 2024. Published by Elsevier B.V.