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Inhibition of endopeptidase and exopeptidase activity of cathepsin B impairs extracellular matrix degradation and tumour invasionMitrović, Ana ...Cathepsin B is a lysosomal cysteine protease that is implicated in a number ofphysiological processes, including protein turnover in lysosomes. Changes inits expression are associated with a variety ... of pathological processes, including cancer. Due to the structural feature, termed the occluding loop, cathepsin B differs from other cysteine proteases in possessing both, endopeptidase and exopeptidase activity. Here we investigated the impact of both cathepsin B activities on intracellular and extracellular collagen IV degradation and tumour cell invasion using new selective synthetic inhibitors,2-{[(8-hydroxy-5-nitroquinoline-7- yl)methyl]amino}-acetonitrile (1), 8-(4-methylpiperidin-1-yl)-5-nitroquinoline (2) and 7-[(4-methylpiperidin-1yl)methyl]-5-nitroquinolin-8-ol (3). All three compounds (5 microm) reduced extracellular degradation of collagen IV by MCF-10A neoT cells by 45-70% as determined by spectrofluorimetry and they (50 microm) attenuated intracellular collagen IV degradation by 40-60% as measured with flow cytometry. Furthermore, all three compounds (5 microm) impaired MCF-10A neoT cell invasion by 40-80% as assessed by measuring electrical impedance in real time. Compounds 1 and 3 (5 microm), but not compound 2, significantly reduced the growth of MMTV-PyMT multicellular tumour spheroids. Collectively, these data suggest that the efficient strategy to impair harmful cathepsin B activity in tumour progression may include simultaneous and potent inhibition of cathepsin B endopeptidase and exopeptidase activities.Source: Biological chemistry. - ISSN 1431-6730 (Vol. 397, issue 2, 2016, str.165-174)Type of material - article, component part ; adult, seriousPublish date - 2016Language - englishCOBISS.SI-ID - 3979633
Link(s):
http://www.degruyter.com/view/j/bchm.2016.397.issue-2/hsz-2015-0236/hsz-2015-0236.xmlDostop samo z geslom
DOI
Author
Mitrović, Ana |
Mirković, Bojana |
Sosič, Izidor |
Gobec, Stanislav, 1970- |
Kos, Janko, 1959-
Topics
anti-tumour activity |
cancer |
cathepins |
inhibitors |
proteases
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Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Mitrović, Ana | 36440 |
Mirković, Bojana | 29604 |
Sosič, Izidor | 30816 |
Gobec, Stanislav, 1970- | 15284 |
Kos, Janko, 1959- | 04648 |
Source: Personal bibliographies
and: SICRIS
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