Nitric oxide enhances the growth of U937 human leukemic cells through a cyclooxygenase-mediated pathway

Abstract

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/G 2 ؉M-phase and decreased G 0 /G 1 -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 mitogenactivated protein kinase inhibitor. SNP treatment resulted in a dose-dependent increase in prostaglandin E 2 (PGE 2 ) production. Furthermore, the addition of exogenous PGE 2 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 PGE 2 may be an effector molecule for NO-regulated cell proliferation. Our data provide a mechanistic insight into the regulatory role of NO in myelopoiesis. J. Leukoc. Biol. 64: 451-458; 1998.

Immune Complex-Induced, Nitric Oxide-Mediated Vascular Endothelial Cell Death by Phagocytes Is Prevented with Decoy FcγReceptors

“…The cDNA was then analyzed for the differential expression of pro-apoptotic genes ( Fig 5 ). It has been shown that, by 24hr 0.5mM of SNAP produces around 100μM of nitrite in the culture medium [ 37 ], which is very close to the NO secreted by RAW264.7 cells in our experiments ( Fig 2 ). Exogenously administered NO significantly upregulated the pro-apoptotic genes such as BAK (35fold), BAX (15 fold), cytochrome-C (12 fold), and caspase-3 (30 fold) when compared to untreated cells ( Fig 5A–5D ).…”