Non-Photoinduced Biological Properties of Verteporfin
Non-Photoinduced Biological Properties of Verteporfin
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DOI：
10.2174/0929867323666160316125048
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发表时间：
2016-01-01
影响因子：
4.1
通讯作者：
Cotelle, Philippe
中科院分区：
文献类型：
--
作者：
Gibault, Floriane;Corvaisier, Matthieu;Cotelle, Philippe
背景：维替泊芬是一种卟啉类光敏剂，临床上用于年龄相关性黄斑变性的光动力学治疗。它几乎同时被鉴定为雅普/TEAD和自噬体抑制剂。在过去的几年中，雅普（TAZ），Hippo途径的下游效应物，已经成为有希望的抗癌靶点，如几个实验证据所示，显示雅普在几种癌症中的过量产生。然而，雅普也被发现与自噬、线粒体和活性氧/氮物种密切相关。本文综述了近年来VP作为雅普/TEAD抑制剂或蛋白质寡聚化促进剂的研究进展，重点介绍了VP对自噬相关的雅普/TEAD基因靶点和其他生物标志物的影响。结果如下：自从VP被鉴定为雅普/TEAD抑制剂以来，几项体外和体内研究已经揭示了这种分子在不同癌症中的新潜力，其中雅普过表达。然而，关于它与雅普相互作用的详细结构信息仍然缺乏。同时，VP通过促进p62的寡聚化被鉴定为自噬体抑制剂。此外，VP在结直肠癌中被证明是肿瘤选择性蛋白毒性的（通过p62，STAT 3的寡聚化）。迄今为止唯一可用的雅普抑制剂的生物学特性的知识对于其在细胞和动物模型上的药理学用途至关重要。结论：VP是一种多靶点药物，可与多种参与细胞主要过程的蛋白质相互作用。虽然这不影响其临床应用，但VP似乎不是雅普/TEAD药理学抑制的理想药物。
Background: Verteporfin is a porphyrinic photosensitizer clinically used for the photodynamic treatment of age-related macular degeneration. It has been identified almost simultaneously as a YAP/TEAD and an autophagosome inhibitor. Over the last few years, YAP (TAZ), the downstream effectors of the Hippo pathway, have emerged as promising anticancer targets, as shown by several experimental lines of evidence, showing the overproduction of YAP in several cancers. However, YAP was also found to be closely connected to autophagy, mitochondria and reactive oxygen/nitrogen species. We herein, review the recent studies where VP was used without photoactivation as a YAP/TEAD inhibitor or protein oligomerization promoter, focusing on its effects on the YAP/TEAD gene targets and other biomarkers related to autophagy. Results: Since the identification of VP as YAP/TEAD inhibitor, several in vitro and in vivo studies have revealed the new potential of this molecule in different cancers, where YAP is overexpressed. However, detailed structural information about its interaction with YAP is still lacking. Concomitantly, VP was identified as autophagosome inhibitor by promoting oligomerization of p62. Moreover, VP proves to be tumor-selective proteotoxic (by oligomerization of p62, STAT3) in colorectal cancer. Knowledge on the biological properties of the only YAP inhibitor available to date is vital for its pharmacological use on cellular and animal models. Conclusion: VP is a multi-target drug interacting with several proteins implicated in major cellular processes. Although this does not impact its clinical use, VP does not seem to be the ideal drug for pharmacological inhibitions of YAP/TEAD.