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 cells 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 microM in
mesothelioma cells, 97.3 microM in DND-1A cells and 93.5 microM in HeLa cells, while those for inhibition of
collagen-induced Ca2+ movements were slightly higher (170.2 microM in
mesothelioma cells and 112.3 microM in HeLa cells) and the value of IC50 for inhibition of
thrombin-induced Ca2+ fluxes (evaluated only in
mesothelioma cells) was lower (22.5 microM). The
drug dose-dependently also inhibited the in vitro growth of
tumor cells; values of IC50 for growth inhibition were 21.8 microM in
mesothelioma cells, 9.1 microM in DND-1A cells and 6.4 microM in HeLa cells, suggesting that the antiproliferative activity of
verapamil was partly Ca(2+)-independent. These data may be 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.