Document Detail

Ondansetron but not granisetron affect cell volume regulation and potassium ion transport of glioma cells treated with estramustine phosphate.
MedLine Citation:
PMID:  12200602     Owner:  NLM     Status:  MEDLINE    
PURPOSE: Highly 5-HT(3)-receptor-specific antiemetic agents may have different effects on ion transport of tumour cells during treatment with cytotoxic drugs. Cell volume regulation, which is dependent on potassium ion (K(+)) flux, is involved the control of cell growth, proliferation, and apoptosis. K(+)-flux response mechanisms to the antiemetics ondansetron and granisetron were therefore correlated to malignant glioma cell (Mg251) volume response to estramustine phosphate (EMP) in vitro. METHODS: We quantified the influx and efflux of potassium ions (using the K(+) analogue (86)Rb(+)) as well as cell volume changes (with image analysis) of glioma cells incubated with the 5-HT(3)-receptor antagonists ondansetron and granisetron (0.1 micro mol/l) combined with 40 mg/l EMP. RESULTS: The EMP-induced cell volume increase was fully inhibited by ondansetron but not affected by granisetron. Ondansetron retained high cellular K(+)-efflux and reduced Na(+), K(+), 2Cl(-)-cotransport activity, whereas granisetron (0.1 micro mol/l) reduced K(+)-efflux and retained an augmented Na(+), K(+), 2Cl(-)-cotransport activity in the presence of 40 mg/l EMP. CONCLUSIONS: Ondansetron affects K(+) transport with ensuing effects on cell volume of tumour cells treated with EMP, whereas granisetron does not. Since ondansetron and other 5-HT(3)-receptor antagonists are used routinely to prevent nausea during anticancer treatment, an increased awareness of possible interactions with the antitumour efficacy of anticancer drugs seems warranted.
Parviz Behnam-Motlagh; Per-Erik Sandström; Roger Henriksson; Kjell Grankvist
Publication Detail:
Type:  Comparative Study; Journal Article     Date:  2002-08-10
Journal Detail:
Title:  Journal of cancer research and clinical oncology     Volume:  128     ISSN:  0171-5216     ISO Abbreviation:  J. Cancer Res. Clin. Oncol.     Publication Date:  2002 Aug 
Date Detail:
Created Date:  2002-08-29     Completed Date:  2002-11-21     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7902060     Medline TA:  J Cancer Res Clin Oncol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  449-55     Citation Subset:  IM    
Department of Clinical Chemistry, Umeå University, 901 85 Umeå, Sweden.
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MeSH Terms
Antineoplastic Agents, Alkylating / pharmacology*
Brain Neoplasms / metabolism,  pathology*
Cell Size / drug effects*
Estramustine / pharmacology*
Glioma / metabolism,  pathology*
Granisetron / pharmacology
Ion Transport / drug effects*
Ondansetron / pharmacology
Potassium / metabolism*
Rubidium Radioisotopes
Serotonin / pharmacology
Serotonin Antagonists / pharmacology*
Sodium / metabolism
Sodium-Potassium-Chloride Symporters / metabolism
Sodium-Potassium-Exchanging ATPase / metabolism
Tumor Cells, Cultured
Reg. No./Substance:
0/Antineoplastic Agents, Alkylating; 0/Rubidium Radioisotopes; 0/Serotonin Antagonists; 0/Sodium-Potassium-Chloride Symporters; 109889-09-0/Granisetron; 2998-57-4/Estramustine; 50-67-9/Serotonin; 7440-09-7/Potassium; 7440-23-5/Sodium; 99614-02-5/Ondansetron; EC ATPase

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