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Diverging effects of 5-HT3 receptor antagonists ondansetron and granisetron on estramustine-inhibited cellular

P Behnam-Motlagh1, P E Sandström, R Henriksson

  • 1Department of Clinical Chemistry, Umeå University, Sweden.

Pharmacology & Toxicology
|June 8, 2001
PubMed

Insights

Ondansetron reversed estramustine phosphate-induced potassium influx reduction in mesothelioma cells, unlike granisetron. This difference stems from distinct effects on ion transport, highlighting varied impacts of antiemetics on cancer cells during chemotherapy.

Area of Science:

  • Oncology
  • Pharmacology
  • Cell Physiology

Background:

  • Estramustine phosphate is an anticancer drug with known effects on cellular ion transport.
  • 5-HT3 receptor antagonists, such as ondansetron and granisetron, are commonly used antiemetics.
  • The interaction between cytotoxic drugs and antiemetics on cancer cell ion transport is not fully understood.

Purpose of the Study:

  • To investigate the effects of ondansetron and granisetron on potassium (K+) influx in P31 mesothelioma cells treated with estramustine phosphate.
  • To elucidate the mechanisms underlying the differential effects of these 5-HT3 receptor antagonists on cellular ion transport.

Main Methods:

  • Utilized 86Rubidium (86Rb+) as a potassium analogue to measure K+ influx.
  • Exposed P31 mesothelioma cells to estramustine phosphate, ondansetron, and granisetron at specific concentrations and durations.
  • Assessed the activity of Na+, K+-ATPase and Na+, K+, 2Cl--cotransport.

Main Results:

  • Estramustine phosphate significantly reduced 86Rb+ influx by 18.7%.
  • Ondansetron inhibited this reduction, while granisetron augmented it.
  • Ondansetron's effect was linked to increased Na+, K+-ATPase and Na+, K+, 2Cl--cotransport activity; granisetron's effect was mainly due to Na+, K+-ATPase inhibition.

Conclusions:

  • Ondansetron uniquely reverses estramustine phosphate-induced K+ influx reduction in tumor cells, unlike granisetron.
  • Differential effects on Na+, K+-ATPase and Na+, K+, 2Cl--cotransport explain the distinct actions of ondansetron and granisetron.
  • Highly 5-HT3 receptor-specific antiemetics can exhibit varied impacts on tumor cell ion transport during cytotoxic therapy.

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