TY - JOUR
T1 - Platelet agonists induce Ca2+ transients in tumor cells by opening distinct receptor-operated channels
T2 - An effect unrelated to the presence of classical multi-drug resistance phenotype
AU - Moroni, M.
AU - Porta, C.
AU - Tua, A.
AU - Magnone, S.
AU - Grignani, G.
PY - 1998
Y1 - 1998
N2 - Background - Modulation of the cytoplasmic calcium concentration is a mechanism of signal transduction regulating several biological phenomena and may also play a role in the stimulation of cell proliferation. In the present study we have investigated the effect of different platelet agonists on cytoplasmic Ca2+ levels in tumor cells with or without the multi-drug resistance (MDR) phenotype and the effects of verapamil on agonist induced Ca2+ transients and on in-vitro tumor cell growth. Methods - LoVo cells and doxorubicin-resistant LoVoDx cells, derived from a human colon adenocarcinoma, were cultured in vitro using standard methods. Cytoplasmic Ca2+ levels in aequorin-loaded tumor cells were determined in a Platelet Ionized Calcium Aggregometer. Results - ADP, GRGDS, PAF, collagen and thrombin were able to induce Ca2+ transients in both cell lines, while U46619, a thromboxane A2 mimetic agent, PDGF and carbachol were not. Tumor cells of both cell lines became refractory to thrombin after the first addition, but remained sensitive to the other inducers. Furthermore, the calcium channel blocker verapamil significantly inhibited thrombin-induced Ca2+ fluxes in both LoVo cells and LoVoDx cells and had no significant effect on Ca2+ movements induced by the other agonists. Finally, the drug inhibited the in-vitro growth of both cell lines in a dose-dependent manner, with an effect more evident in resistant cells. Conclusions. - These data may help to explain the ability of verapamil to reverse the MDR phenotype and may contribute to identifying new mechanisms for the two-way interaction of tumors with the hemostatic system.
AB - Background - Modulation of the cytoplasmic calcium concentration is a mechanism of signal transduction regulating several biological phenomena and may also play a role in the stimulation of cell proliferation. In the present study we have investigated the effect of different platelet agonists on cytoplasmic Ca2+ levels in tumor cells with or without the multi-drug resistance (MDR) phenotype and the effects of verapamil on agonist induced Ca2+ transients and on in-vitro tumor cell growth. Methods - LoVo cells and doxorubicin-resistant LoVoDx cells, derived from a human colon adenocarcinoma, were cultured in vitro using standard methods. Cytoplasmic Ca2+ levels in aequorin-loaded tumor cells were determined in a Platelet Ionized Calcium Aggregometer. Results - ADP, GRGDS, PAF, collagen and thrombin were able to induce Ca2+ transients in both cell lines, while U46619, a thromboxane A2 mimetic agent, PDGF and carbachol were not. Tumor cells of both cell lines became refractory to thrombin after the first addition, but remained sensitive to the other inducers. Furthermore, the calcium channel blocker verapamil significantly inhibited thrombin-induced Ca2+ fluxes in both LoVo cells and LoVoDx cells and had no significant effect on Ca2+ movements induced by the other agonists. Finally, the drug inhibited the in-vitro growth of both cell lines in a dose-dependent manner, with an effect more evident in resistant cells. Conclusions. - These data may help to explain the ability of verapamil to reverse the MDR phenotype and may contribute to identifying new mechanisms for the two-way interaction of tumors with the hemostatic system.
KW - Ca transients
KW - Cell growth
KW - Multi-drug resistance
KW - Platelet agonists
KW - Verapamil
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M3 - Article
AN - SCOPUS:0031828896
VL - 11
SP - 141
EP - 146
JO - Cancer Journal from Scientific American
JF - Cancer Journal from Scientific American
SN - 1528-9117
IS - 3
ER -