Inhibitors of cathepsins B and L induce autophagy and cell death in neuroblastoma cells
| Autor: | Robert W. Mason, Donna M. Cartledge, Rita Colella, Lisa Glazewski, Guizhen Lu |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Programmed cell death
Cathepsin L Antineoplastic Agents Biology Article Cathepsin B Mice Neuroblastoma Cell Line Tumor medicine Animals Humans Cytotoxic T cell Pharmacology (medical) Cell Proliferation Pharmacology Cathepsin Mice Inbred BALB C Cell Death Cell growth Autophagy medicine.disease Xenograft Model Antitumor Assays Molecular biology Mice Mutant Strains Oncology Cell Death Process Cancer research |
| Zdroj: | Investigational New Drugs. 31:20-29 |
| ISSN: | 1573-0646 0167-6997 |
| DOI: | 10.1007/s10637-012-9826-6 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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