Dual effect of flurbiprofen on cell proliferation and agonist-induced Ca(2+) movement in human osteosarcoma cells.
In human MG63 osteosarcoma cells, the effect of flurbiprofen on intracellular Ca(2+) concentrations ([Ca(2+)](i)) and proliferation was explored. The proliferation was enhanced by 20-120 microM flurbiprofen, and was decreased by 140-200 microM flurbiprofen. The effect of flurbiprofen on the increases in cytosolic free Ca(2+) levels ([Ca(2+)](i)) induced by ATP, bradykinin, histamine and thapsigargin (an inhibitor of the endoplasmic reticulum Ca(2+) ATPase), was examined. In cell preincubated with 20 or 80 microM flurbiprofen, the [Ca(2+)](i) increases induced by all agonists were attenuated. In the presence of 20 microM flurbiprofen, the decreased [Ca(2+)](i) responses with the agonists were attributed to a defective Ca(2+) influx because this decrease was unobserved in agonists-induced [Ca(2+)](i) increases in the absence of extracellular Ca(2+). In the presence of 80 microM flurbiprofen, both the Ca(2+) influx component and the Ca(2+) releasing (from organelles) component were defective. These results suggest that flurbiprofen could alter proliferation and inhibit [Ca(2+)](i) increases.
Tseng
Li-Ling
LL
Department of Dentistry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 813.
Cheng
He-Hsiung
HH
Huang
Chun-Jen
CJ
Liu
Shiuh-Inn
SI
Kuo
Chun-Chi
CC
Chen
Wei-Chuan
WC
Huang
Jong-Khing
JK
Hsu
Shu-Shong
SS
Chang
Hong-Tai
HT
Kao
Cheng-Hsing
CH
Ho
Chin-Man
CM
Jan
Chung-Ren
CR
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000819:agonists / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005480:Flurbiprofen / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D012516:Osteosarcoma; D019284:Thapsigargin / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005480:Flurbiprofen; D019284:Thapsigargin; D006632:Histamine; D000255:Adenosine Triphosphate; D001920:Bradykinin; D002118:Calcium