Study of in vitro and in vivo effects of the piperidine nitroxide Tempol—a potential new therapeutic agent for gliomas

The identification of novel therapeutic agents for the management of malignant gliomas represents an area of active research. Here, we show that Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl; TPL), a stable nitroxide free radical, inhibits the growth of C6 glioma cells both in vitro and in...

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Bibliographic Details
Published in:European journal of cancer (1990) 2003-04, Vol.39 (6), p.829-837
Main Authors: Gariboldi, M.B, Ravizza, R, Petterino, C, Castagnaro, M, Finocchiaro, G, Monti, E
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Antitumour effects
Apoptosis
Biological and medical sciences
Blotting, Western
Central Nervous System Neoplasms - drug therapy
Central Nervous System Neoplasms - pathology
Chemotherapy
Cyclic N-Oxides - therapeutic use
Cyclin-Dependent Kinase Inhibitor p21
Cyclins - analysis
Drug Screening Assays, Antitumor
Glioma
Immunohistochemistry
Medical sciences
Mice
Neoplasm Transplantation
Neurology
p21waf1/cip1
Pharmacology. Drug treatments
Rats
Spin Labels
Tempol
Transplantation, Heterologous
Tumor Cells, Cultured
Tumor Suppressor Protein p53 - analysis
Tumors of the nervous system. Phacomatoses
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Summary:The identification of novel therapeutic agents for the management of malignant gliomas represents an area of active research. Here, we show that Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl; TPL), a stable nitroxide free radical, inhibits the growth of C6 glioma cells both in vitro and in vivo. Morphological features of apoptosis were apparent in C6 cells following in vitro treatment with TPL. Cell death was preceded by dose-dependent increase in p21waf1/cip1 expression, without apparent stabilisation of the TP53 gene product. When C6 cells were grown as xenografts in nude mice, treatment with TPL induced a significant dose-dependent decrease in tumour growth, without signs of general or organ toxicity. Tumours from treated mice showed an increase in the number of apoptotic cells and a decrease in the rate of neo-vascularisation compared with tumours from control mice. Our findings suggest a potential use for TPL as a novel antiproliferative agent for the treatment of malignant gliomas.
ISSN:0959-8049
1879-0852
DOI:10.1016/S0959-8049(02)00742-6