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Molecular and Chemical Neuropathology

, Volume 22, Issue 2, pp 81–95 | Cite as

Inhibition of cell growth and intracellular Ca2+ mobilization in human brain tumor cells by Ca2+ channel antagonists

  • Yong Soo Lee
  • Mohammed M. Sayeed
  • Robert D. Wurster
Original Articles

Abstract

The effects of various Ca2+ channel agonists and antagonists on tumor cell growth were investigated using U-373 MG human astrocytoma and SK-N-MC human neuroblastoma cell lines. Classical Ca2+ channel antagonists, verapamil, nifedipine, and diltiazem, and inorganic Ca2+ channel antagonists, Ni2+ and Co2+, inhibited growth of these tumor cells in a dose-dependent manner. Except Ni2+, these Ca2+ channel antagonists did not induce a significant cytotoxicity, suggesting that the growth-inhibitory effects of these drugs may be the result of the influence on the proliferative signaling mechanisms of these tumor cells. In contrast, Bay K-8644, a Ca2+ channel agonist, neither enhanced the growth of tumor cells nor increased intracellular Ca2+ concentration, indicating that voltage-sensitive Ca2+ channels may not be involved in tumor cell proliferation. Moreover, growth-inhibitory concentrations of Ca2+ channel antagonists significantly blocked agonist (carbachol or serum)-induced intracellular Ca2+ mobilization, which was monitored using Fura-2 fluorescence technique. These results suggest that the inhibition of the growth of human brain tumor cells induced by Ca2+ channel antagonists may not be the result of interaction with Ca2+ channels, but may be the result of the interference with agonist-induced intracellular Ca2+ mobilization, which is an important proliferative signaling mechanism.

Index Entries

Ca2+ channel antagonists astrocytoma neuroblastoma intracellular Ca2+ tumor cell proliferation voltagesensitive Ca2+ channels 

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Copyright information

© Humana Press 1994

Authors and Affiliations

  • Yong Soo Lee
    • 1
  • Mohammed M. Sayeed
    • 1
  • Robert D. Wurster
    • 1
  1. 1.Departments of Physiology and Neurological SurgeryLoyola University Medical CenterMaywood

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