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Investigational New Drugs

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01.02.2013 | PRECLINICAL STUDIES

Inhibitors of cathepsins B and L induce autophagy and cell death in neuroblastoma cells

verfasst von: Donna M. Cartledge, Rita Colella, Lisa Glazewski, Guizhen Lu, Robert W. Mason

Erschienen in: Investigational New Drugs | Ausgabe 1/2013

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Summary

This study was designed to test the hypothesis that specific inhibition of cathepsins B and L will cause death of neuroblastoma cells. Five compounds that differ in mode and rate of inhibition of these two enzymes were all shown to cause neuroblastoma cell death. Efficacy of the different compounds was related to their ability to inhibit the activity of the isolated enzymes. A dose- and time-response for induction of cell death was demonstrated for each compound. A proteomic study showed that inhibitor treatment caused an increase of markers of cell stress, including induction of levels of the autophagy marker, LC-3-II. Levels of this marker protein were highest at cytotoxic inhibitor concentrations, implicating autophagy in the cell death process. An in vivo mouse model showed that one of these inhibitors markedly impaired tumor growth. It is concluded that development of drugs to target these two proteases may provide a novel approach to treating neuroblastoma.

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Titel: Inhibitors of cathepsins B and L induce autophagy and cell death in neuroblastoma cells
verfasst von: Donna M. Cartledge
Rita Colella
Lisa Glazewski
Guizhen Lu
Robert W. Mason
Publikationsdatum: 01.02.2013
Verlag: Springer US
Erschienen in: Investigational New Drugs / Ausgabe 1/2013
Print ISSN: 0167-6997
Elektronische ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-012-9826-6

Neu im Fachgebiet Onkologie

24.04.2024 | DGIM 2024 | Nachrichten

Springer Medizin

Inhibitors of cathepsins B and L induce autophagy and cell death in neuroblastoma cells

Summary

Neu im Fachgebiet Onkologie

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Krebspatienten impfen: Was? Wen? Und wann nicht?

Müde im Alter? Auch an die Nebenniere denken

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Springer Medizin

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