Cathepsin L, target in cancer treatment?

Lankelma, Jacqueline M.; Voorend, Daniëlle M.; Barwari, Temo; Koetsveld, Joris; Spek, Anne H van der; Porto, Alexander P. N. A. de; Rooijen, Geeske van; Noorden, C. J. F. Van

doi:10.1016/j.lfs.2009.11.016

Cited by 158 publications

(169 citation statements)

References 85 publications

(126 reference statements)

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“…Recently, nuclear-localized CTSL involved in cancer has been revealed, suggesting that CTSL may have key roles in the nucleus beyond its known lysosomal and extracellular activities 11,[16][17][18][19] . Although the therapeutic potential of CTSL inhibitors has not been fully characterized in preclinical studies, targeting CTSL activity is considered as a strategy for anticancer therapy 20 .…”

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confidence: 99%

Selective cancer targeting with prodrugs activated by histone deacetylases and a tumour-associated protease

et al. 2013

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Eradication of cancer cells while minimizing damage to healthy cells is a primary goal of cancer therapy. Highly selective drugs are urgently needed. Here we demonstrate a new prodrug strategy for selective cancer therapy that utilizes increased histone deacetylase (HDAC) and tumour-associated protease activities produced in malignant cancer cells. By coupling an acetylated lysine group to puromycin, a masked cytotoxic agent is created, which is serially activated by HDAC and an endogenous protease cathepsin L (CTSL) that remove the acetyl group first and then the unacetylated lysine group liberating puromycin. The agent selectively kills human cancer cell lines with high HDAC and CTSL activities. In vivo studies confirm tumour growth inhibition in prodrug-treated mice bearing human cancer xenografts. This cancer-selective cleavage of the masking group is a promising strategy for the next generation of anticancer drug development that could be applied to many other cytotoxic agents.

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confidence: 99%

Selective cancer targeting with prodrugs activated by histone deacetylases and a tumour-associated protease

et al. 2013

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“…for NB invasion and metastasis, cathepsin L was chosen for further reviewing (Lankelma et al 2010). Cathepsin L is also involved in the development of drug resistance (Zheng et al 2004).…”

Section: R219mentioning

confidence: 99%

“…Loss of cell adhesion and digestion of the extracellular matrix are processes that allow the invasion and migration of cancer cells (Cairns et al 2003, Gocheva et al 2006. Cathepsin L seems to be involved in these processes (Lankelma et al 2010). Indeed, the active isoforms of cathepsin L can be found, not only intracellularly (liposomes, cytoplasm and nucleus) but also in the extracellular matrix (Zheng et al 2009).…”

Section: S Verissimo Et Al: Novel Neuroblastoma Targetsmentioning

confidence: 99%

“…Indeed, the active isoforms of cathepsin L can be found, not only intracellularly (liposomes, cytoplasm and nucleus) but also in the extracellular matrix (Zheng et al 2009). Owing to an increase in anaerobic glycolysis, the tumour cells are in an acidic environment (Lankelma et al 2010). In these acidic conditions, cathepsin L is active and digests components of the extracellular matrix, such as collagen types I and IV (Skrzydlewska et al 2005).…”

Section: S Verissimo Et Al: Novel Neuroblastoma Targetsmentioning

confidence: 99%

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Neuroblastoma therapy: what is in the pipeline?

Veríssimo¹,

Molenaar²,

Fitzsimons³

et al. 2011

Endocrine-Related Cancer

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Despite the expansion of knowledge about neuroblastoma (NB) in recent years, the therapeutic outcome for children with a high-risk NB has not significantly improved. Therefore, more effective therapies are needed. This might be achieved by aiming future efforts at recently proposed but not yet developed targets for NB therapy. In this review, we discuss the recently proposed molecular targets that are in clinical trials and, in particular, those that are not yet explored in the clinic. We focus on the selection of these molecular targets for which promising in vitro and in vivo results have been obtained by silencing/inhibiting them. In addition, these selected targets are involved at least in one of the NB tumorigenic processes: proliferation, anti-apoptosis, angiogenesis and/or metastasis. In particular, we will review a recently proposed target, the microtubule-associated protein (MAP) encoded by doublecortin-like kinase gene (DCLK1). DCLK1-derived MAPs are crucial for proliferation and survival of neuroblasts and are highly expressed not only in NB but also in other tumours such as gliomas. Additionally, we will discuss neuropeptide Y, its Y2 receptor and cathepsin L as examples of targets to decrease angiogenesis and metastasis of NB. Furthermore, we will review the micro-RNAs that have been proposed as therapeutic targets for NB. Detailed investigation of these not yet developed targets as well as exploration of multi-target approaches might be the key to a more effective NB therapy, i.e. increasing specificity, reducing toxicity and avoiding long-term side effects.

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“…Cathepsin L is a survival protein that confers resistance to cancer cell apoptosis [22,23] . The expression of cathepsin L is exclusively elevated in cancer cells and can be easily screened for small-molecule inhibitors [24,25] ; therefore, it may serve as a better therapeutic target than other cathepsins [26][27][28] .…”

Section: Introductionmentioning

confidence: 99%

Inhibition of cathepsin L sensitizes human glioma cells to ionizing radiation in vitro through NF-κB signaling pathway

Yang

Wang

et al. 2015

Acta Pharmacol Sin

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Aim: Cathepsin L, a lysosomal cysteine proteinase, is exclusively elevated in a variety of malignancies, including gliomas. In this study we investigated the relationship between cathepsin L and NF-κB, two radiation-responsive elements, in regulating the sensitivity of human glioma cells ionizing radiation (IR) in vitro. Methods: Human glioma U251 cells were exposed to IR (10 Gy), and the expression of cathepsin L and NF-κB was measured using Western blotting. The nuclear translocation of NF-κB p65 and p50 was analyzed with immunofluorescence assays. Cell apoptosis was examined with clonogenic assays. NF-κB transcription and NF-κB-dependent cyclin D1 and ATM transactivation were monitored using luciferase reporter and ChIP assays, respectively. DNA damage repair was investigated using the comet assay.

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Cathepsin L, target in cancer treatment?

Cited by 158 publications

References 85 publications

Selective cancer targeting with prodrugs activated by histone deacetylases and a tumour-associated protease

Selective cancer targeting with prodrugs activated by histone deacetylases and a tumour-associated protease

Neuroblastoma therapy: what is in the pipeline?

Inhibition of cathepsin L sensitizes human glioma cells to ionizing radiation in vitro through NF-κB signaling pathway

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