Laboratori d`Enginyeria de Proteines, Departament de Biologia, Facultat de Ciencies, Universitat de Girona, Campus de Montilivi, Maria Aurelia Capmany 40, 17003, Girona, Spain.
Curr Med Chem. 2018;25(30):3540-3559. doi: 10.2174/0929867325666180309112023.
Research in the field of antitumor chemotherapeutics pursues a key issue, drug selectivity for cancer cells. In the last 20 years, a group of proteins has attracted scientific interest as cancer chemotherapeutics due to their ability to specifically kill cancer cells while leaving normal cells undamaged. One of these proteins is apoptin.
In this study, the recent available literature regarding cell death mechanisms induced by apoptin has been reviewed. Delivering this drug to tumor cells is a challenge because it spontaneously forms soluble non-covalent aggregates. This led us to include in this review the different approaches for obtaining the maximum efficiency of apoptin entry to cancer cells.
This review provides an up-to-date summary of the mechanisms by which apoptin induces selective apoptosis in tumor cells while leaving normal cells undamaged. It highlights the relationship between the apoptosis mechanism induced by this protein and its functional motifs. Apoptin has been described as an intrinsically disordered protein, which explains its ability to interact with multiple partners and affect multiple pathways inside the cell. Characterization of the different partners and pathways induced by apoptin has begun to shed light on the molecular basis of apoptin's tumor-selective cytotoxicity.
The findings confirm the interest in apoptin as a potentially safe antitumor drug. Research still needed to be conducted to find an effective way to deliver apoptin for use in clinics.
抗肿瘤化学疗法领域的研究追求一个关键问题，即癌细胞的药物选择性。在过去的 20 年中，由于其能够特异性杀死癌细胞而不损伤正常细胞的能力，一组蛋白质引起了科学界的兴趣，作为癌症化学疗法。其中一种蛋白质是凋亡素。
本研究回顾了最近关于凋亡素诱导细胞死亡机制的可用文献。将这种药物递送到肿瘤细胞是一个挑战，因为它会自发形成可溶性非共价聚集物。这导致我们在本综述中包括了获得凋亡素进入癌细胞的最大效率的不同方法。
本综述提供了最新的总结，说明凋亡素如何诱导肿瘤细胞选择性凋亡而不损伤正常细胞。它强调了这种蛋白质诱导的凋亡机制与其功能基序之间的关系。凋亡素被描述为一种固有无序的蛋白质，这解释了它与多个伴侣相互作用并影响细胞内多个途径的能力。对凋亡素诱导的不同伴侣和途径的表征开始揭示凋亡素肿瘤选择性细胞毒性的分子基础。
这些发现证实了凋亡素作为一种潜在安全的抗肿瘤药物的兴趣。仍需要进行研究以找到有效方法将凋亡素用于临床。
