Oelkrug Christopher, Hartke Martin, Schubert Andreas
Fraunhofer Institute for Cell Therapy and Immunology (IZI), Leipzig, Germany
Fraunhofer Institute for Cell Therapy and Immunology (IZI), Leipzig, Germany.
Anticancer Res. 2015 Feb;35(2):635-43.
Although cancer belongs to one of the leading causes of death around the world, fortunately studies have shown that tumor cells have various targets that are susceptible to attack. Interestingly, tumor cells are comprised of cellular membranes, which are altered in chemical composition relative to non-neoplastic cells, giving them an increased net negative charge. These altered membranes are ideal targets for antimicrobial peptides (AMPs) shown to have additional tumoricidal properties and, hence, named anticancer peptides (ACPs). Several hundred ACPs have been explored in vitro and in vivo on various types of cancer. Novel anticancer agents are supposed not to cause serious side effects and the formation of multidrug-resistant tumor cells. During the quest for potent ACPs, promising candidates were isolated from skin secretions of amphibians, such as the granular glands of the Chinese brown frog, Rana chensinensis. ACPs have to be selective to cancer cells and should not induce strong immune responses or be cleared from the body rapidly. Several modifications can improve ACPs either by optimizing the primary structure rationally or randomly or even by introducing other chemical modifications.
尽管癌症是全球主要死因之一,但幸运的是,研究表明肿瘤细胞有各种易受攻击的靶点。有趣的是,肿瘤细胞由细胞膜组成,其化学成分相对于非肿瘤细胞有所改变,使其净负电荷增加。这些改变的膜是抗菌肽(AMPs)的理想靶点,抗菌肽已显示出具有额外的杀肿瘤特性,因此被命名为抗癌肽(ACPs)。已经在体外和体内对数百种抗癌肽针对各种类型的癌症进行了研究。新型抗癌药物应该不会引起严重的副作用,也不会形成多药耐药肿瘤细胞。在寻找有效的抗癌肽的过程中,从两栖动物的皮肤分泌物中分离出了有前景的候选物,比如中国林蛙的颗粒腺。抗癌肽必须对癌细胞具有选择性,不应诱导强烈的免疫反应,也不应迅速从体内清除。通过合理或随机优化一级结构,甚至引入其他化学修饰,几种修饰方法可以改善抗癌肽。