Kos Janko, Mitrović Ana, Mirković Bojana
Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia.
Future Med Chem. 2014 Jul;6(11):1355-71. doi: 10.4155/fmc.14.73.
Cathepsin B is a lysosomal cysteine peptidase, with an important role in the development and progression of cancer. It is involved in the degradation of extracellular matrix proteins, a process promoting invasion and metastasis of tumor cells and tumor angiogenesis. Cathepsin B is unique among cathepsins in possessing both carboxypeptidase and endopeptidase activities. While the former is associated with its physiological role, the latter is involved in pathological degradation of the extracellular matrix. Its activities are regulated by different means, the most important being its endogenous inhibitors, the cystatins. In cancer this peptidase/inhibitor balance is altered, leading to harmful cathepsin B activity. The latter can be prevented by exogenous inhibitors. They differ in modes of inhibition, size, structure, binding affinity, selectivity, toxicity and bioavailability. In this article, we review the properties and function of endogenous and exogenous cathepsin B inhibitors and indicate their application as possible anticancer agents.
组织蛋白酶B是一种溶酶体半胱氨酸肽酶，在癌症的发生和发展中起重要作用。它参与细胞外基质蛋白的降解，这一过程促进肿瘤细胞的侵袭和转移以及肿瘤血管生成。组织蛋白酶B在组织蛋白酶中独一无二，兼具羧肽酶和内肽酶活性。前者与其生理作用相关，后者则参与细胞外基质的病理性降解。其活性通过不同方式调节，其中最重要的是其内源性抑制剂胱抑素。在癌症中，这种肽酶/抑制剂平衡发生改变，导致组织蛋白酶B产生有害活性。后者可通过外源性抑制剂来预防。这些抑制剂在抑制模式、大小、结构、结合亲和力、选择性、毒性和生物利用度方面存在差异。在本文中，我们综述了内源性和外源性组织蛋白酶B抑制剂的特性和功能，并指出它们作为潜在抗癌药物的应用。
