Ondansetron but not granisetron affect cell volume regulation and potassium ion transport of glioma cells treated with estramustine phosphate

Abstract

Purpose. Highly 5-HT₃-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 ⁸⁶Rb⁺) as well as cell volume changes (with image analysis) of glioma cells incubated with the 5-HT₃-receptor antagonists ondansetron and granisetron (0.1 µmol/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 µmol/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-HT₃-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.