Sobrinho Juliana C, Simões-Silva Rodrigo, Holanda Rudson J, Alfonso Jorge, Gomez Ana F, Zanchi Fernando B, Moreira-Dill Leandro S, Grabner Amy N, Zuliani Juliana P, Calderon Leonardo A, Soares Andreimar M
Departamento de Medicina, Universidade Federal de Rondônia, Porto Velho-RO, Brazil.
Curr Pharm Biotechnol. 2016;17(14):1201-1212. doi: 10.2174/1389201017666160808154250.
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.
癌症是一种目前影响约1400万人的疾病，其特征是细胞生长异常且复制能力改变，导致肿瘤块的形成且不受细胞凋亡控制。对化疗所用药物的耐药性及其副作用促使科研人员寻找对抗这种疾病的新疗法。来自动植物的具有抗肿瘤细胞细胞毒性活性的分子因其有可能成为药物来源而受到研究。在这方面，蛇毒含有多种已被证明具有生物技术潜力的蛋白质和肽。在多项研究中，已观察到其抗菌作用和抗肿瘤活性。研究最为广泛的毒液成分之一是磷脂酶A2。蛇毒磷脂酶A2（svPLA2s）是一大类催化磷脂sn-2位水解以释放脂肪酸和溶血磷脂的分子，并且与广泛的生物技术活性相关。除了对某些肿瘤细胞系具有特定的细胞毒性外，还描述了其对血管生成、黏附和细胞迁移的抑制活性。svPLA2s的抗肿瘤活性在体外和体内均有观察到，但对于这些蛋白质促进这种活性的作用机制知之甚少。在这篇综述中，将讨论svPLA2s的主要结构和功能特征，以及迄今为止提出的解释其抗肿瘤活性的机制，着眼于其作为癌症治疗替代方案的潜在用途。
