Nitric oxide enhances the growth of U937 human leukemic cells through a cyclooxygenase-mediated pathway.
The mechanisms of exogenous nitric oxide (NO)-enhanced growth of the U937 human myeloid leukemic cells were examined using sodium nitroprusside (SNP) as a NO donor. Treatment with 0.1 mM SNP for 72 h caused a 45 +/- 2% increase in U937 cell growth with significantly increased S/G2+M-phase and decreased G0/G1-phase of the cell cycle. The growth-enhancing effect of SNP was blocked by indomethacin, a cyclooxygenase inhibitor, but not by H7, a broad spectrum kinase inhibitor, or PD98059, a mitogen-activated protein kinase inhibitor. SNP treatment resulted in a dose-dependent increase in prostaglandin E2 (PGE2) production. Furthermore, the addition of exogenous PGE2 not only enhanced U937 cell growth but restored the indomethacin-inhibited mitogenic effect of SNP. We suggest that NO can enhance cell growth through activating the cyclooxygenase pathway and that PGE2 may be an effector molecule for NO-regulated cell proliferation. Our data provide a mechanistic insight into the regulatory role of NO in myelopoiesis.
Institute of Physiology, School of Life Science, National Yang-Ming University, Taipei, Taiwan, Republic of China.
J C
JC
Jea
T C
TC
Liu
S Y
SY
Wang
Y J
YJ
Sung
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D047428:Protein Kinase Inhibitors; D020298:U937 Cells / Q000166:cytology / Q000187:drug effects
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D005419:Flavonoids; D020030:Nitric Oxide Donors; D047428:Protein Kinase Inhibitors; D009599:Nitroprusside; D009569:Nitric Oxide; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D007213:Indomethacin