Transmembrane ion flux modifiers verapamil and ouabain modulate cytotoxic effects of extracellular ATP on human tumor cells in vitro

P. Correale, M. Caraglia, A. Procopio, M. R. Marinetti, R. Guarrasi, A. Fabbrocini, A. R. Bianco, P. Tagliaferri

Research output: Contribution to journalArticlepeer-review

Abstract

Extracellular ATP can often induce tumor cell cytotoxicity; however, the molecular mechanisms of these effects are mostly unknown. We investigated whether modifications in transmembrane ion fluxes are involved in the determination of ATP-cytotoxicity. We have found that cultured human tumor cells derived from colon (LoVo) and lung (A549) carcinomas are resistant to ATP, while LoVo-Dx cells (a doxorubicin-resistant derivative of LoVo cells) and melanoma GLL-19 cells are highly sensitive to this nucleotide. 48 h exposure to 100 nM verapamil increases sensitivity of LoVo and A549 cells to ATP. This effect is completely reverted by the addition of the calcium ionophore A23187. Conversely, 4 h exposure to 100 nM ouabain, which blocks the Na+/K+ exchange pump, neutralyzes ATP cytotoxicity against LoVo-Dx and GLL-19 cells. Furthermore, ATP-mediated cytotoxic effects on these cells are completely antagonized by ADP-β-S, a non hydrolyzable analogue of ATP. These findings suggest that transmembrane ion flux modifications play a critical role in ATP cytotoxicity and that ATP binding on surface receptors and probably nucleotide hydrolysis are needed for inducing cytotoxicity on human tumor cells.

Original languageEnglish
Pages (from-to)847-851
Number of pages5
JournalInternational Journal of Oncology
Volume3
Issue number5
Publication statusPublished - 1993

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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