INFlUENCE OF ARGININE METABOLITES ON HUMAN TUMOR CELL VIABILITY UPON ARGININE DEPRIVATION IN VITRO
DOI: http://dx.doi.org/10.30970/sbi.0502.148
Abstract
In human organism arginine is necessary not only for protein synthesis but it also serves as a precursor for a number of important biologically active substances that influence cell growth and viability. These substances include such arginine metabolites as polyamines, nitric oxide, agmatine, ornithine and urea. It is known that in vitro tumor cells substantially differ in the level of sensitivity to arginine deprivation, which is reflected in the dynamics of apoptotic manifestations under these conditions. Identification of the molecular reasons of this phenomenon is important for optimization of the regimes of arginine deprivation-based anticancer enzymotherapy. One of possible reasons of the various level of sensitivity of tumor cells to arginine deprivation may reside in differences in their susceptibility to arginine catabolites withdrawal. Therefore, we aimed to investigate the effect of exogenous arginine metabolites (polyamines putrescine and spermine, as well as agmatine, nitric oxide, ornithine and urea) under arginine deprived conditions on viability and proliferative potential of two human cancer cell lines (A549 lung carcinoma and HepG2 hepatocarcinoma) that differ in the level of sensitivity to arginine depletion. It was revealed that none of the studied arginine catabolite affected cancer cell viability and proliferative potential in arginine-free medium, independently of the level of their sensitivity to arginine starvation. Thus, despite the complexity and versatility of arginine metabolic networks, the depletion of metabolites of this amino acid is not a key reason that determines differences in cell response to arginine deprivation. Therefore, identification of signaling mechanisms that underlie apoptosis induction in cancer cells upon arginine starvation needs to be further elucidated.
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1. Arndt M.A., Battaglia V., Parisi E. et al. The arginine metabolite agmatine protects mitochondrial function and confers resistance to cellular apoptosis. Am. J. Physiol. Cell Physiol, 2009; 296(6): 1411-1419. | |
| |
2. Basuroy U.K., Gerner E.W. Emerging concepts in targeting the polyamine metabolic pathway in epithelial cancer chemoprevention and chemotherapy. J. Biochem, 2006; 139(1): 27-33. | |
| |
3. 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; 34(11): 1085-1089. | |
| |
4. Cheng P.N., Lam T.L., Lam W.M. et al. Pegylated recombinant human arginase (rhArg-peg5000 mw) inhibits the in vitro and in vivo proliferation of human hepatocellular carcinoma through arginine depletion. Cancer Res, 2007; 67(1): 309-317. | |
| |
5. Glazer E.S., Piccirillo M., Albino V. et al. Phase II study of pegylated arginine deiminase for nonresectable and metastatic hepatocellular carcinoma. J. Clin. Oncol, 2010; 28(13): 2220-2226. | |
| |
6. Hill J.M., Roberts J., Loeb E. et al. L-asparaginase therapy for leukemia and other malignant neoplasms: remission in human leukemia. JAMA, 1967; 202(9): 882-888. | |
| |
7. Kuo M.T., Savaraj N., Feun L.G. Targeted cellular metabolism for cancer chemotherapy with recombinant arginine-degrading enzymes. Oncotarget, 2010; 1(4): 246-251. | |
| |
8. Morris S.M. Arginine: beyond protein. Am. J. Clin. Nutr, 2006; 83(2): 508S-512S. | |
| |
9. Morris S.M. Arginine metabolism: boundaries of our knowledge. J. Nutr, 2007; 137(6): 1602S-1609S. | |
| |
10. Nakauchi T., Ando A., Ueda-Yamada M. et al. Prevention of ornithine cytotoxicity by nonpolar side chain amino acids in retinal pigment epithelial cells. Invest. Ophthalmol. Vis. Sci, 2003; 44(11): 5023-5028. | |
| |
11. 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(6): 800-810. | |
| |
12. Tan Y., Xu M., Hoffman R.M. Broad selective efficacy of recombinant methioninase and polyethylene glycol-modified recombinant methioninase on cancer cells in vitro. Anticancer Res, 2010; 30(4): 1041-1046. | |
| |
13. 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(2): 148-157. | |
| |
14. Wheatley D.N. Arginine deprivation and metabolomics: important aspects of intermediary metabolism in relation to the differential sensitivity of normal and tumour cells. Semin. Cancer Biol, 2005; 15(4): 247-253. | |
| |
15. Wheatley D.N., Philip R., Campbell E. Arginine deprivation and tumour cell death: Arginase and its inhibition. Mol. Cell Biochem, 2003; 244():177-185. | |
| |
16. Wink D.A., Vodovotz Y., Laval J. et al. The multifaceted roles of nitric oxide in cancer. Carcinogenesis, 1998; 19(5): 711-721. | |
| |
17. Wu G., Morris S.M. Arginine metabolism: nitric oxide and beyond. Biochem. J, 1998; 336(1): 1-17. | |
| |
18. Zou C., Vlastos A.T., Yang L. et al. Effects of difluoromethylornithine on growth inhibition and apoptosis in human cervical epithelial and cancerous cell lines. Gynecol. Oncol, 2002; 85(2): 266-273. |
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