Anti-Cancer Compounds Targeted to VDAC: Potential and Perspectives.
Anti-Cancer Compounds Targeted to VDAC: Potential and Perspectives.
复制标题
DOI：
10.2174/0929867324666170530074039
复制
发表时间：
2018-01
影响因子：
4.1
通讯作者：
S. Reina;V. De Pinto
中科院分区：
文献类型：
--
作者：
S. Reina;V. De Pinto
VDAC （Voltage-Dependent Anion selective Channel，电压依赖性阴离子选择通道）是一个位于线粒体外膜的丰富的成孔蛋白小家族。它们的作用范围很广，从最直观的，由于其β -桶结构通过膜形成亲水性管道，到鲜为人知的功能，使它们成为生物能量代谢和细胞质成分之间的串讲中的重要角色。由于这种定位，特别是VDAC1被报道参与细胞凋亡、己糖激酶和微管蛋白结合，以及Warburg效应。由于这些原因，VDAC在癌症中的参与被认为是必然的，许多化合物已经被提出并用于实验试验，以证明影响VDAC功能的分子的功效。在这项工作中，我们因此回顾了描述药物化合物通过VDAC作用于癌细胞增殖的文献。主要分为三类：作用于VDAC-己糖激酶结合的分子，直接抑制VDAC传导的分子，影响VDAC基因表达水平的分子。本文还讨论了生物多肽在这方面的应用。结论由于对VDAC蛋白功能特性的认识尚不充分，VDAC作为抗癌的药理靶点仍是一个非常开放但非常有前景的领域。
BACKGROUND VDAC (Voltage-Dependent Anion selective Channel) is a small family of abundant pore-forming proteins located in the outer mitochondrial membrane. Their role range from the most intuitive, the formation of a hydrophilic conduit through the membrane thanks to its beta-barrel structure, to less understood functions that make them essential actors in the cross-talk between the bioenergetics metabolism and the cytosol components. Due to this localization, VDAC1, in particular, has been reported to be involved in apoptosis, Hexokinase and tubulin binding, and in the Warburg effect. For these reasons, an involvement of VDAC in cancer is considered consequential and a number of compounds have been proposed and used in experimental trials to demonstrate the efficacy of molecules affecting the functions of VDAC. OBJECTIVES In this work, we thus survey the literature describing drug compounds acting on the cancerous proliferation through VDAC. Three main categories have been assigned: molecules acting on the VDAC-Hexokinase binding, molecules directly inhibiting the VDAC conductance, molecules affecting the expression levels of the VDAC gene. The application of biological peptides for this purpose is also considered. CONCLUSION Since the knowledges about the functional properties of VDAC protein are still insufficient, VDAC as a pharmacological target in the fight against cancer is still a very open, but very promising, field.