Levels of biological markers of nitric oxide in serum of patients with squamous cell carcinoma of the oral cavity

Abstract

An evaluation of the levels of nitric oxide (NO) and two markers of NO activity in the blood of people with oral cancer highlights possible roles for these compounds in cancer progression. Wioletta Ratajczak-Wrona and colleagues at the Medical University of Bialystok, Poland, measured the levels of NO and the markers — malonyldialdehyde and nitrotyrosine — in 24 people with squamous cell carcinoma of the oral cavity, before and after surgical removal of a tumor. Concentrations of NO were greatest in individuals with advanced disease, consistent with the body mounting an immune attack. Following treatment, these concentrations dropped, suggesting a role for tumor cells in the secretion of this molecule. Malonyldialdehyde and nitrotyrosine levels followed different patterns, indicating that their production may not depend entirely on NO concentration. These compounds might also affect tumor development in different ways.

Keywords

malonyldialdehyde / nitric oxide / nitrotyrosine / squamous cell carcinoma of the oral cavity

References

[1] Chen AY, Myers JN. Cancer of the oral cavity. Dis Mon, 2001, 47(7): 275-361.

[2] Massano J, Regateiro FS, Januario G. Oral squamous cell carcinoma: review of prognostic and predictive factors. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2006, 102(1): 67-76.

[3] Moncada S, Higgs EA. Molecular mechanisms and therapeutic strategies related to nitric oxide. FASEB J, 1995, 9(13): 1319-1330.

[4] Xu W, Liu LZ, Loizidou M. The role of nitric oxide in cancer. Cell Res, 2002, 12(5/6): 311-320.

[5] Ohashi M, Iwase M, Nagumo M. Elevated production of salivary nitric oxide in oral mucosal diseases. J Oral Pathol Med, 1999, 28(8): 355-359.

[6] Sumitani K, Kamijo R, Nagumo M. Cytotoxic effect of sodium nitroprusside on cancer cells: involvement of apoptosis and suppression of c-myc and c-myb proto-oncogene expression. Anticancer Res, 1997, 17(2A): 865-871.

[7] Shang ZJ, Li JR, Li ZB. Effects of exogenous nitric oxide on oral squamous cell carcinoma: an in vitro study. J Oral Maxillofac Surg, 2002, 60(8): 905-911.

[8] Sandau KB, Fandrey J, Brüne B. Accumulation of HIF-1α under the influence of nitric oxide. Blood, 2001, 97(4): 1009-1015.

[9] Vaupel P. The role of hypoxia-induced factors in tumor progression. Oncologist, 2004, 9(5): 10-17.

[10] Koukourakis MI, Giatromanolaki A, Sivridis E. Hypoxia-inducible factor (HIF1A and HIF2A), angiogenesis, and chemoradiotherapy outcome of squamous cell head-and-neck cancer. Int J Radiat Oncol Biol Phys, 2002, 53(5): 1192-1202.

[11] Dix TA, Aikens J. Mechanisms and biological relevance of lipid peroxidation initiation. Chem Res Toxicol, 1993, 6(1): 2-18.

[12] Kourie JI. Interaction of reactive oxygen species with ion transport mechanisms. Am J Physiol, 1998, 275(1): 1-24.

[13] McConnell EJ, Bittelmeyer AM, Raess BU. Irreversible inhibition of plasma membrane (Ca²⁺+Mg²⁺)-ATPase and Ca²⁺ transport by 4-OH-2,3-trans-nonenal. Arch Biochem Biophys, 1999, 361(2): 252-256.

[14] Tyurina YY, Shvedova AA, Kawai K. Phospholipid signaling in apoptosis: peroxidation and externalization of phosphatidylserine. Toxicology, 2000, 148(2/3): 93-101.

[15] Hanafy KA, Krumenacker JS, Murad F. NO, nitrotyrosine, and cyclic GMP in signal transduction. Med Sci Monit, 2001, 7(4): 801-819.

[16] Hughes MN. Relationships between nitric oxide, nitroxyl ion, nitrosonium cation and peroxynitrite. Biochim Biophys Acta, 1999, 1411(2/3): 263-272.

[17] American Joint Committee on Cancer. Manual for Staging of Cancer. 4th ed. Philadelphia: JB Lippincott, 1992.

[18] Jablonska E, Kiersnowska-Rogowska B, Ratajczak W. Reactive oxygen and nitrogen species in the course of B-CLL. Adv Med Sci, 2007, 52(1): 154-158.

[19] Singh S, Gupta AK. Nitric oxide: role in tumour biology and iNOS/NO-based anticancer therapies. Cancer Chemother Pharmacol, 2011, 67(6): 1211-1224.

[20] Wink DA, Mitchell JB. Chemical biology of nitric oxide: insights into regulatory, cytotoxic, and cytoprotective mechanisms of nitric oxide. Free Radic Biol Med, 1998, 25(4/5): 434-456.

[21] Beevi SS, Rasheed AM, Geetha A. Evaluation of oxidative stress and nitric oxide levels in patients with oral cavity cancer. Jpn J Clin Oncol, 2004, 34(7): 379-385.

[22] Rasheed MH, Beevi SS, Geetha A. Enhanced lipid peroxidation and nitric oxide products with deranged antioxidant status in patients with head and neck squamous cell carcinoma. Oral Oncol, 2007, 43(4): 333-338.

[23] Gokul S, Patil VS, Jailkhani R. Oxidant-antioxidant status in blood and tumor tissue of oral squamous cell carcinoma patients. Oral Dis, 2010, 16(1): 29-33.

[24] Jablonska E, Puzewska W, Charkiewicz M. Effect of IL-18 on leukocyte expression of iNOS and phospho-IkappaB in patients with squamous cell carcinoma of the oral cavity. Neoplasma, 2006, 53(3): 200-205.

[25] Gavilanes J, Moro MA, Lizasoain I. Nitric oxide synthase activity in human squamous cell carcinoma of the head and neck. Laryngoscope, 1999, 109(1): 148-152.

[26] Brennan PA, Thomas GJ, Langdon JD. The role of nitric oxide in oral diseases. Arch Oral Biol, 2003, 48(2): 93-100.

[27] Connelly ST, Macabeo-Ong M, Dekker N. Increased nitric oxide levels and iNOS over-expression in oral squamous cell carcinoma. Oral Oncol, 2005, 41(3): 261-267.

[28] Thomsen LL, Scott JM, Topley P. Selective inhibition of inducible nitric oxide synthase inhibits tumor growth in vivo: studies with 1400 w, a novel inhibitor. Cancer Res, 1997, 57(1): 3300-3304.

[29] Ambs S, Hussain SP, Harris CC. Interactive effects of nitric oxide and the p53 tumor suppressor gene in carcinogenesis and tumor progression. FASEB J, 1997, 11(6): 443-448.

[30] Gallo O, Masini E, Morbidelli L. Role of nitric oxide in angiogenesis and tumor progression in head and neck cancer. J Natl Cancer Inst, 1998, 90(8): 587-596.

[31] Morbidelli L, Chang CH, Douglas JG. Nitric oxide mediates mitogenic effect of VEGF on coronary venular endothelium. Am J Physiol, 1996, 170(1 Pt 2): 411-415.

[32] Kawamata H, Uchida D, Hamano H. Active-MMP2 in cancer cell nests of oral cancer patients: correlation with lymph node metastasis. Int J Oncol, 1998, 13(4): 699-704.

[33] Kurahara S, Shinohara M, Ikebe T. Expression of MMPS, MT-MMP, and TIMPs in squamous cell carcinoma of the oral cavity: correlations with tumor invasion and metastasis. Head Neck, 1999, 21(7): 627-638.

[34] Maeda H, Noguchi Y, Sato K. Enhanced vascular permeability in solid tumor is mediated by nitric oxide and inhibited by both new nitric oxide scavenger and nitric oxide synthase inhibitor. Jpn J Cancer Res, 1994, 85(4): 331-334.

[35] Przybyszewski W, Kasperczyk J, Stoklosa K. [DNA damage induced by products of lipid peroxidation.]. Post Hig Med Dosw, 2005, 59(17): 75-81.

[36] Torun M, Yardim S, Gonenc A. Serum beta-carotene, vitamin E, vitamin C and malondialdehyde levels in several types of cancer. J Clin Pharm Ther, 1995, 20(5): 259-263.

[37] Sabitha KE, Shyamaladevi CS. Oxidant and antioxidant activity changes in patients with oral cancer and treated with radiotherapy. Oral Oncol, 1999, 35(3): 273-277.

[38] Korde SD, Basak A, Chaudhary M. Enhanced nitrosative and oxidative stress with decreased total antioxidant capacity in patients with oral precancer and oral squamous cell carcinoma. Oncology, 2011, 80(5/6): 382-389.

[39] Broncel M, Balcerak M, Bała A. [The erythrocyte membrane structure in patients with mixed hyperlipidemia.]. Wiad Lek, 2007, 60(1/2): 4-9.

[40] Yeo WS, Lee SJ, Lee JR. Nitrosative protein tyrosine modifications: biochemistry and functional significance. J Biochem Mol Biol, 2008, 41(3): 194-203.

[41] Mantovani A, Allavena P, Sica A. Cancer-related inflammation. Nature, 2008, 454(7221): 436-444.