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组织蛋白酶 B 在癌症进展中的作用:配位化合物的潜在靶点。

Role of Cathepsin B in Cancer Progression: A Potential Target for Coordination Compounds.

机构信息

Department of Chemistry, Federal University of Sao Carlos, Sao Carlos, Sao Paulo CEP 13.565-905, Brazil.

出版信息

Mini Rev Med Chem. 2021;21(13):1612-1624. doi: 10.2174/1389557521666210212152937.

Abstract

A member of cathepsin enzymes called Cathepsin B is a cysteine-protease enzyme that plays significant role in metalloproteinase regulation. Cathepsin B stands out amidst other members of cathepsin because of its role in both normal body physiology and pathophysiology. Being an antiapoptotic and a pro-apoptotic agent, Cathepsin B has been reported to have deleterious effects, especially when its expression, activities, and distribution are outrageous. The over-expression of cathepsin B is traceable to dysregulation of one or more regulated steps involved in its synthesis. Consequently, the over-expression of cathepsin B contributes to the pathogenesis of different types of cancers - a global menace. Interestingly, the synthesis of this enzyme has been reported to be inhibited by several metal compounds, thus, curbing its involvement in carcinogenesis. In this review, the synthesis, structure, localization, and roles of cathepsin B in carcinogenesis were explored. Likewise, we also discussed the capacity of metallic compounds to inhibit this enzyme. Metals such as gold, ruthenium, palladium, Iridium, and Tellurium demonstrated remarkable activity toward cathepsin B of different modes. A relationship between cytotoxicity and inhibition constants was observed.

摘要

组织蛋白酶 B 是组织蛋白酶家族中的一员,是一种半胱氨酸蛋白酶,在金属蛋白酶的调控中发挥着重要作用。组织蛋白酶 B 之所以能在众多家族成员中脱颖而出,是因为其在正常生理和病理生理过程中都发挥着作用。作为一种抗凋亡和促凋亡的介质,组织蛋白酶 B 已被报道具有有害作用,尤其是当其表达、活性和分布失控时。组织蛋白酶 B 的过度表达可归因于其合成过程中一个或多个调控步骤的失调。因此,组织蛋白酶 B 的过度表达导致了多种类型癌症的发病机制,这是一个全球性的威胁。有趣的是,据报道,几种金属化合物可以抑制这种酶的合成,从而抑制其在致癌作用中的参与。在这篇综述中,探讨了组织蛋白酶 B 在致癌作用中的合成、结构、定位和作用。同样,我们也讨论了金属化合物抑制这种酶的能力。金、钌、钯、铱和碲等金属对不同模式的组织蛋白酶 B 表现出显著的活性。观察到细胞毒性和抑制常数之间存在关系。

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