Document Detail

Sensitization to hyperthermia by intracellular acidification of C6 glioma cells.
MedLine Citation:
PMID:  9821105     Owner:  NLM     Status:  MEDLINE    
Hyperthermia has been introduced as a new modality of treatment for glioma. In these experiments, the cytotoxicity of hyperthermia in C6 glioma cells was enhanced by increasing the intracellular acidity with amiloride and/or 4,4'-diisothiocyanatostilbene-2,2' disulfonic acid (DIDS). Intracellular pH (pHi) is regulated mainly by Na+/H+ and HCO3-/Cl- antiports through the cell membrane, and amiloride acts on the former, DIDS on the latter to lower pHi. The cellular thermosensitivity to clinically achievable brain hyperthermia at 42 degrees C was enhanced by 0.5 mM amiloride (Na+/H+ antiport inhibitor). T0 values (T0 = the heating period required to reduce experimental survival rate by 1/e) at 42 degrees C without and with amiloride was 192 and 81 min, respectively. The addition of DIDS (HCO3-/Cl- antiport inhibitor) further enhanced. T0 value was 25 min. Fluorophotometric measurement of pHi was employed using the pH sensitive dye, bis(carboxyethyl)carboxyfluorescein, which is trapped in viable cells. The average pHi in control C6 glioma cells in pH 7.2 media was 7.21. In the untreated cells heated at 42 degrees C for 1 hour, the pHi was 7.12. The pHi of the cells heated in the presence of amiloride was decreased to 6.83. The pHi was further lowered to 6.67 by the treatment with amiloride in combination with DIDS for 2 hours. Hyperthermia with amiloride and DIDS may be a more effective treatment for malignant gliomas.
R Kitai; M Kabuto; T Kubota; H Kobayashi; H Matsumoto; S Hayashi; H Shioura; T Ohtsubo; K Katayama; E Kano
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neuro-oncology     Volume:  39     ISSN:  0167-594X     ISO Abbreviation:  J. Neurooncol.     Publication Date:  1998 Sep 
Date Detail:
Created Date:  1999-02-09     Completed Date:  1999-02-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8309335     Medline TA:  J Neurooncol     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  197-203     Citation Subset:  IM    
Department of Neurosurgery, Fukui Medical School, Japan.
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MeSH Terms
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / therapeutic use*
Amiloride / therapeutic use*
Brain Neoplasms / drug therapy,  therapy*
Cell Survival / drug effects
Glioma / drug therapy,  therapy*
Hydrogen-Ion Concentration
Hyperthermia, Induced / methods*
Sodium-Hydrogen Antiporter / antagonists & inhibitors*
Tumor Cells, Cultured
Reg. No./Substance:
0/Acids; 0/Sodium-Hydrogen Antiporter; 2609-46-3/Amiloride; 53005-05-3/4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid

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