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 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 p21(WAF1/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.
Gariboldi
M B
MB
DBSF, Laboratory of Pharmacology, University of Insubria, Busto Arsizio (VA), Italy.
Ravizza
R
R
Petterino
C
C
Castagnaro
M
M
Finocchiaro
G
G
Monti
E
E
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003497:Cyclic N-Oxides / Q000627:therapeutic use*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis; D004354:Drug Screening Assays, Antitumor; D007150:Immunohistochemistry; D051379:Mice; D009368:Neoplasm Transplantation; D051381:Rats; D013113:Spin Labels; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
C493957:Cdkn1a protein, mouse; C493958:Cdkn1a protein, rat; D003497:Cyclic N-Oxides; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D013113:Spin Labels; D016159:Tumor Suppressor Protein p53; C001803:tempol