Cysteine cathepsins as a prospective target for anticancer therapies—current progress and prospects

Pogorzelska, Aneta; Żołnowska, Beata; Bartoszewski, Rafał

doi:10.1016/j.biochi.2018.05.023

Cited by 39 publications

(31 citation statements)

References 279 publications

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“…Normal cells and cancer cells have defense mechanisms to protect against cell death by LMP. The cystatin family is composed of stefins, cystatins, and kininogens, and they are endogenous cysteine cathepsin inhibitors [ 44 ]. In addition, HSP70 modulates lysosome membrane integrity.…”

Section: Discussionmentioning

confidence: 99%

Induction of Lysosomal Membrane Permeabilization Is a Major Event of FTY720-Mediated Non-Apoptotic Cell Death in Human Glioma Cells

Min

Kwon

2020

Cancers

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FTY720, a sphingosine-1-phosphate (S1P) receptor modulator, is a synthetic compound produced by the modification of a metabolite from I. sinclairii. Here, we found that FTY720 induced non-apoptotic cell death in human glioma cells (U251MG, U87MG, and U118MG). FTY720 (10 µM) dramatically induced cytoplasmic vacuolation in glioma cells. However, FTY720-mediated vacuolation and cell death are not associated with autophagy. Genetic or pharmacological inhibition of autophagy did not inhibit FTY720-induced cell death. Herein, we detected that FTY720-induced cytoplasmic vacuoles were stained with lysotracker red, and FTY720 induced lysosomal membrane permeabilization (LMP). Interestingly, cathepsin inhibitors (E64D and pepstatin A) and ectopic expression of heat shock protein 70 (HSP70), which is an endogenous inhibitor of LMP, markedly inhibited FTY720-induced cell death. Our results demonstrated that FTY720 induced non-apoptotic cell death via the induction of LMP in human glioma cells.

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Section: Discussionmentioning

confidence: 99%

Induction of Lysosomal Membrane Permeabilization Is a Major Event of FTY720-Mediated Non-Apoptotic Cell Death in Human Glioma Cells

Min

Kwon

2020

Cancers

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“…Over the years the central importance of the Cathepsins in disease have been intensely explored, particularly in the context of tumor proliferation, metastasis, invasion, ECM degradation, angiogenesis [13] and inflammation [14]. Consequently, it is with these perspectives in mind that the driving force behind Cathepsin research has broadly diversified with significant progress being made in certain areas of applied research, such as antibody-drug conjugates, diagnostic imaging and their use in targeted drug delivery [14,15].…”

Section: The Cathepsins and Cancermentioning

confidence: 99%

‘Patchiness’ and basic cancer research: unravelling the proteases

2019

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The recent developments in Cathepsin protease research have unveiled a number of key observations which are fundamental to further our understanding of normal cellular homeostasis and disease. By far, the most interesting and promising area of Cathepsin biology stems from how these proteins are linked to the fate of living cells through the phenomenon of Lysosomal Leakage and Lysosomal Membrane Permeabilisation. While extracellular Cathepsins are generally believed to be of central importance in tumour progression, through their ability to modulate the architecture of the Extracellular Matrix, intracellular Cathepsins have been established as being of extreme significance in mediating cell death through Apoptosis. With these two juxtaposed key research areas in mind, the focus of this review highlights recent advancements in how this fastpaced area of Cathepsin research has recently evolved in the context of their mechanistic regulation in cancer research.

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“…Due to their high reactivity and lack of selectivity, E-64 and its cell-permeable derivative E-64d are not applicable to clinical practice. However, E-64 represents the lead compound for the development of new inhibitors with increased selectivity (reviewed in [ 90 , 152 , 153 , 155 ]). As a derivative of E-64, the potent and selective cathepsin B inhibitor CA-074 was synthesized [ 107 ], and its low membrane permeability was improved by methylation of the carboxyl group [ 166 ].…”

Section: Introductionmentioning

confidence: 99%

The role of cysteine peptidases in coronavirus cell entry and replication: The therapeutic potential of cathepsin inhibitors

et al. 2020

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Over the last 2 decades, several coronaviruses (CoVs) have crossed the species barrier into humans, causing highly prevalent and severe respiratory diseases, often with fatal outcomes. CoVs are a large group of enveloped, single-stranded, positive-sense RNA viruses, which encode large replicase polyproteins that are processed by viral peptidases to generate the nonstructural proteins (Nsps) that mediate viral RNA synthesis. Papain-like peptidases (PLPs) and chymotrypsin-like cysteine 3C-like peptidase are essential for coronaviral replication and represent attractive antiviral drug targets. Furthermore, CoVs utilize the activation of their envelope spike glycoproteins by host cell peptidases to gain entry into cells. CoVs have evolved multiple strategies for spike protein activation, including the utilization of lysosomal cysteine cathepsins. In this review, viral and host peptidases involved in CoV cell entry and replication are discussed in depth, with an emphasis on papain-like cysteine cathepsins. Furthermore, important findings on cysteine peptidase inhibitors with regard to virus attenuation are highlighted as well as the potential of such inhibitors for future treatment strategies for CoV-related diseases.

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Cysteine cathepsins as a prospective target for anticancer therapies—current progress and prospects

Cited by 39 publications

References 279 publications

Induction of Lysosomal Membrane Permeabilization Is a Major Event of FTY720-Mediated Non-Apoptotic Cell Death in Human Glioma Cells

Induction of Lysosomal Membrane Permeabilization Is a Major Event of FTY720-Mediated Non-Apoptotic Cell Death in Human Glioma Cells

‘Patchiness’ and basic cancer research: unravelling the proteases

The role of cysteine peptidases in coronavirus cell entry and replication: The therapeutic potential of cathepsin inhibitors

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