Dual effect of flurbiprofen on cell proliferation and agonist-induced Ca2+ movement in human osteosarcoma cells

In human MG63 osteosarcoma cells, the effect of flurbiprofen on intracellular Ca2+ concentrations ([Ca2+](i)) and proliferation was explored. The proliferation was enhanced by 20-120 mu M flurbiprofen, and was decreased by 140-200 mu M flurbiprofen. The effect of flurbiprofen on the increases in cytosolic free Ca2+ levels ([Ca2+](i)) induced by ATP, bradykinin, histamine and thapsigargin (an inhibitor of the endoplasmic reticulum Ca2+ ATPase), was examined. In cell preincubated with 20 or 80 mu M flurbiprofen, the [Ca2+](i) increases induced by all agonists were attenuated. In the presence of 20 mu M flurbiprofen, the decreased [Ca2+](i) responses with the agonists were attributed to a defective Ca2+ influx because this decrease was unobserved in agonists-induced [Ca2+](i) increases in the absence of extracellular Ca2+. In the presence of 80 mu M flurbiprofen, both the Ca2+ influx component and the Ca2+ releasing (from organelles) component were defective. These results suggest that flurbiprofen could alter proliferation and inhibit [Ca2+](i) increases.