INHIBITION OF CELL-GROWTH AND INTRACELLULAR CA2-TUMOR CELLS BY CA2+ CHANNEL ANTAGONISTS( MOBILIZATION IN HUMAN BRAIN)

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 antagonist s, verapamil, nifedipine, and diltiazem, and inorganic Ca2+ channel an tagonists, Ni2+ and Co2+, inhibited growth of these tumor cells in a d ose-dependent manner. Except Ni2+, these Ca2+ channel antagonists did not induce a significant cytotoxicity, suggesting that the growth-inhi bitory effects of these drugs may be the result of the influence on th e proliferative signaling mechanisms of these tumor cells. In contrast , Bay K-8644, a Ca2+ channel agonist, neither enhanced the growth of t umor 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+ cha nnel antagonists significantly blocked agonist (carbachol or serum)-in duced 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 antagon ists may not be the result of interaction with Ca2+ channels, but may be the result of the interference with agonist-induced intracellular C a2+ mobilization, which is an important proliferative signaling mechan ism.