Verapamil inhibits to different extents agonist-induced Ca2+ transients in human tumor cells and in vitro tumor cell growth

A. Brocchieri, A. Saporiti, M. Moroni, C. Porta, A. Tua, G. Grignani

Research output: Contribution to journalArticlepeer-review

Abstract

Platelet agonists are known to contribute to the regulation of cytoplasmic Ca2+ levels in tumor cells and this property could be relevant in the stimulation of cell proliferation. In the present study we investigated the ability of ADP, collagen and thrombin to increase cytoplasmic Ca2+ levels in different human tumor cell lines (mesothelioma, DND-1A melanoma, HeLa uterine carcinoma) and we analyzed the effect of the calcium channel blocker verapamil on Ca2+ fluxes and on in vitro tumor cell growth. ADP was able to induce a transient increase in the cytoplasmic Ca2+ concentration in tumor eels from all lines; collagen showed this effect in mesothelioma cells and in HeLa cells, and thrombin was effective only in mesothelioma cells. Verapamil inhibited Ca2+ fluxes induced by the effective agonists in a dose-dependent manner. Values of IC50 for inhibition of ADP-induced Ca2+ transients were 63.5 μM in mesothelioma cells, 97.3 μM in DND-1A cells and 93.5 μM in HeLa cells, while those for inhibition of collagen-induced Ca2+ movements were slightly higher (170.2 μM in mesothelioma cells and 112.3 μM in HeLa cells) and the value of IC50 for inhibition of thrombin-induced Ca2+ fluxes (evaluated only in mesothelioma cells) was lower (22.5 μM). The drug dose-dependently also inhibited the in vitro growth of tumor cells; values of IC50 for growth inhibition were 21.8 μM in mesothelioma cells, 9.1 μM in DND-1A cells and 6.4 μM in HeLa cells, suggesting that the antiproliferative activity of verapamil was partly Ca2+-independent. These data maybe of interest to elucidate the mechanisms of the two-way interactions of tumors with the hemostatic system and may help to identify new pharmacologic strategies for their control.

Original languageEnglish
Pages (from-to)56-64
Number of pages9
JournalInvasion and Metastasis
Volume16
Issue number2
Publication statusPublished - 1996

Keywords

  • Ca fluxes
  • Platelet agonists
  • Tumor growth
  • Verapamil

ASJC Scopus subject areas

  • Cancer Research

Fingerprint

Dive into the research topics of 'Verapamil inhibits to different extents agonist-induced Ca2+ transients in human tumor cells and in vitro tumor cell growth'. Together they form a unique fingerprint.

Cite this