This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Feger, F. Articles by Mossalayi, M. D. Search for Related Content PubMed PubMed Citation Articles by Feger, F. Articles by Mossalayi, M. D.

Role of Iron in Tumor Cell Protection from the Pro-Apoptotic Effect of Nitric Oxide¹

Hematology Laboratory, Paris V Faculty of Pharmacy, 75006 Paris, France [F. F., J. B., M. A., L. D., J. N., J-J. G.]; Bone Marrow Transplantation Laboratory, Bordeaux 2 University, 33076 Bordeaux, France [H. F-D., M. M. M., M. D., J. R., M. D. M.]; and Department of Surgery, Berlin University, D-10713 Berlin, Germany [A. K. N.]

F2The host defense against tumor cells is in part based upon the production of nitric oxide (NO) by activated macrophages. However, carcinogenesis may involve mechanisms that protect tumor cells from NO-mediated apoptosis. In the present study, we have assessed the effects of exogenous NO on the proliferation and survival of human liver (AKN-1), lung (A549), skin (HaCat), and pancreatic (Capan-2) tumor cell lines, compared with normal skin-derived epithelial cell cultures. Except to the HaCat cell line, all of the other human epithelioid cells were sensitive to the antiproliferation effect of S-nitroso-N-acetyl-penicillamine or Deta NONOate, whereas tumor cells had low if any response to sodium nitroprusside. Growth inhibition with exogenous NO correlated with increased apoptosis, but was not mediated by cyclic GMP, peroxynitrite generation, or poly(ADP-ribose) polymerase modulation, all of which involved in NO-mediated growth inhibition of normal skin-derived epithelial cell cultures. The simultaneous addition of iron-containing compounds protected tumor cells from NO-mediated growth inhibition and apoptosis. Intracellular iron quantification indicated that, as deferoxamine, exogenous NO significantly decreased intracellular ferric iron levels in tumor cells. Together, the current study reveals that intracellular iron elevation rescues tumor cells from NO-mediated iron depletion and subsequent growth inhibition and apoptosis.

This article has been cited by other articles:

				M. D. Mossalayi, I. Vouldoukis, M. Mamani-Matsuda, T. Kauss, J. Guillon, J. Maugein, D. Moynet, J. Rambert, V. Desplat, D. Mazier, et al. CD23 Mediates Antimycobacterial Activity of Human Macrophages Infect. Immun., December 1, 2009; 77(12): 5537 - 5542. [Abstract] [Full Text] [PDF]

				J. Wang, C. Fillebeen, G. Chen, B. Andriopoulos, and K. Pantopoulos Sodium Nitroprusside Promotes IRP2 Degradation via an Increase in Intracellular Iron and in the Absence of S Nitrosylation at C178. Mol. Cell. Biol., March 1, 2006; 26(5): 1948 - 1954. [Abstract] [Full Text] [PDF]

				J.-H. Yang, W.-D. Le, S. F. Basinger, S. M. Wu, and C.-y. Yang Mechanisms of Apoptosis in Human Retinal Pigment Epithelium Induced by TNF-{alpha} in Conditions of Heavy Metal Ion Deficiency Invest. Ophthalmol. Vis. Sci., March 1, 2005; 46(3): 1039 - 1046. [Abstract] [Full Text] [PDF]