EFFECT OF NITRIC OXIDE DONOR ON VIABILITY OF HUMAN LEUKEMIC CELLS UPON ARGININE DEPRIVATION
DOI: http://dx.doi.org/10.30970/sbi.0502.155
Abstract
Some types of tumor cells are unable to synthesize arginine from its precursors. They exhibit growth inhibition and decreased viability in vitro and in vivo under enzymatic arginine deprivation. However, prolonged arginine starvation in human may cause vasoconstriction and thrombosis due to the deficit of arginine derivative, nitric oxide (NO), as vasodilator and disaggregant. This problem can be overcome via supplementation with exogenous NO-donors in vivo, which, in turn, may produce either, pro-apoptotic or anti-apoptotic specific effects on cancer cells under arginine restriction. In this study we elucidated the effect of exogenous NO donor, sodium nitroprusside (SNP) on the viability of human Jurkat leukemic cells under arginine deprivation in vitro. We observed that arginine deprivation suppressed cell proliferation and led to a rapid decrease in cell viability concomitant with progression of apoptosis. According to SNP IC50 determination and apoptosis assays, NO-donor at physiological concentration did not promote survival of tumor cells in arginine-free medium. Moreover, SNP cytotoxicity for Jurkat cells was increased upon arginine withdrawal, suggesting that application of NO donor in vivo may potentially enhance the therapeutic effect of arginine deprivation.
Keywords
Full Text:
PDFReferences
1. Bansal V., Rodriguez P., Wu G. et al. Citrulline Can Preserve Proliferation and Prevent the Loss of CD3 Chain Under Conditions of Low Arginine. JPEN, 2004; 28(6): 423-430. | |
| |
2. Bobak Y.P., Vynnytska B.O., Kurlishchuk Y.V. et al. Cancer cell sensitivity to arginine deprivation in vitro is not determined by endogenous levels of arginine metabolic enzymes. Cell Biol. Int, 2010; 4: 1085-1090. | |
| |
3. Cheng P.N., Lam T.L., Lam W.M. et al. Pegylated recombinant human arginase (rhArg-peg5000mw) inhibits the in vitro and in vivo proliferation of human hepatocellular carcinoma through arginine depletion. Cancer Res, 2007; 67: 309-317. | |
| |
4. Cheng N.M., Leung Y.C., Lo W.H.: US Patent No. 20050244398. 2005. | |
| |
5. Delage B., Fennell D.A., Nicholson L. et al. Arginine deprivation and argininosuccinate synthetase expression in the treatment of cancer. Int. J. Cancer, 2010; 126: 2762-2772. | |
| |
6. Engeland M., Nieland L.J., Ramaekers F.C. et al. Annexin V-affinity assay: a review on an apoptosis detection system based on phosphatidylserine exposure. Cytometry, 1998; 31: 1-9. | |
| |
7. Feun L., You M., Wu C.J. et al. Arginine deprivation as a targeted therapy for cancer. Curr. Pharm. Des, 2008; 14: 1049-1057. | |
| |
8. Fukumura D., Kashiwagi S., Jain R.K. The role of nitric oxide in tumour progression. Nature Reviews Cancer, 2006; 6: 521-534. | |
| |
9. Glazer E.S., Stone E.M., Zhu C. et al. Bioengineered human arginase I with enhanced activity and stability controls hepatocellular and pancreatic carcinoma xenografts. Transnational Oncology, 2011; 4(3): 138-146. | |
| |
10. Greene L.C., Wagner D.A., Glogowski J. et al. Analysis of nitrate, nitrite and [N15] nitrate in biological fluids. Anal. Biochem, 1982; 126: 131. | |
| |
11. Hernandez C.P., Morrow K., Lopez-Barcons L.A. et al. Pegylated arginase I: a potential therapeutic approach in T-ALL. Blood, 2010; 115: 5214-5221. | |
| |
12. Huerta S., Chilka S., Bonavida B. Nitric oxide donors: Novel cancer therapeutics (Review). Int. J. of Oncology, 2008; 33: 909-927. | |
| |
13. Lam T.L., Wong G.K., Chong H.C. et al. Recombinant human arginase inhibits proliferation of human hepatocellular carcinoma by inducing cell cycle arrest. Cancer Letter, 2009; 277: 91-100. | |
| |
14. Morris S.M. Arginine: beyond protein. Am. J. Clin. Nutr, 2006; 83 (Suppl): 508S-512S. | |
| |
15. Peterson G.L. A simplification of the protein assay method of Lowry et al. which is more generally applicable. Anal. Biochem, 1977; 83: 346-356. | |
| |
16. Scott L., Lamb J., Smith S., Wheatley D.N. Single amino acid (arginine) deprivation: rapid and selective death of cultured transformed and malignant cells. Br. J. Cancer, 2000; 83: 800-810. | |
| |
17. Villalobo A. Nitric oxide and cell proliferation. FEBS, 2006; 273: 2329-2344. | |
| |
18. Vynnytska-Myronovska B., Bobak Y., Garbe Y. et al. Single amino acid arginine starvation efficiently sensitizes cancer cells to canavanine treatment and irradiation Int. J. Cancer, accepted preprint. | |
| |
19. Vynnytska B.O., Mayevska O.M., Kurlishchuk Y.V. et al. Canavanine augments proapoptotic effects of arginine deprivation in cultured human cancer cells. Anticancer Drugs, 2011; 22: 148-157. | |
| |
20. Wang P.G., Xian M., Tang X. et al. Nitric oxide donors: chemical activities and biological applications. Chem. Rev, 2002; 102: 1091-1134. | |
| |
21. Wheatley D.N., Kilfeather R., Stitt A., Campbell E. Integrity and stability of the citrulline-arginine pathway in normal and tumour cell lines. Cancer Letter, 2005; 227: 141-152. | |
| |
22. Weiss G., Welner-Felmayer G., Werner E.R. et al. Iron regulates nitric oxide synthase activity by controlling nuclear transcription. J. Ex Med, 1994; 180: 969-976. | |
Refbacks
- There are currently no refbacks.
Copyright (c) 2011 Studia biologica
This work is licensed under a Creative Commons Attribution 4.0 International License.