Ondansetron but not granisetron affect cell volume regulation and potassium ion transport of glioma cells treated with estramustine phosphate.
OBJECTIVE
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.
Department of Clinical Chemistry, Umeå University, 901 85 Umeå, Sweden.
Parviz
P
Behnam-Motlagh
Per-Erik
PE
Sandström
Roger
R
Henriksson
Kjell
K
Grankvist
D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D048429:Cell Size / Q000187:drug effects*; D004961:Estramustine / Q000494:pharmacology*; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D017829:Granisetron / Q000494:pharmacology; D006801:Humans; D017136:Ion Transport / Q000187:drug effects*; D017294:Ondansetron / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D012414:Rubidium Radioisotopes; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014407:Tumor Cells, Cultured
D018906:Antineoplastic Agents, Alkylating; D004961:Estramustine; D017829:Granisetron; D017294:Ondansetron; D011188:Potassium; D012414:Rubidium Radioisotopes; D012701:Serotonin; D012702:Serotonin Antagonists; D012964:Sodium; D028021:Sodium-Potassium-Chloride Symporters; D000254:Sodium-Potassium-Exchanging ATPase