Melike EROL-DEMİRBİLEK, H. Ferhan KOMURCU, Seref KOMURCU, Nedret KİLİC

Meme ve küçük hücreli olmayan akciğer kanser, hastalarında EGF ve TNF-a düzeyleri ve oksidatif/nitrozatif stres

Malign hücreler yüksek hücre içi reaktif oksijen türleri ve değişmiş antioksidan molekülleri düzeyleri sergilerler. Bu çalışmanın amacı bazı antioksidanların, lipid peroksidasyonu ve protein oksidasyonu ürünlerinin, büyüme faktörü ve sitokinin serum düzeylerini değerlendirmektir. Çalışma 20 meme kanserli, 20 küçük hücreli olmayan akciğer kanserli hasta ve 20 sağlıklı kişiden oluşmuştur. Serumlarda süperoksit dismutaz SOD , glutatyon GSH , nitrik oksit NO , malondialdehit MDA , ileri oksidasyon protein ürünü AOPP , tümör nekroz faktör-alfa TNF-a ve epidermal büyüme faktörü EGF ölçülmüştür. Kanser hastalarında yüksek lipid peroksidasyonu, protein oksidasyonu ve epidermal büyüme faktörü düzeyleri; düşük NO ve TNF- düzeyleri gözlenmiştir. Bütün kanser gruplarında artmış serum GSH derişimi ve azalmış SOD aktiviteleri bulunmuştur. Çalışmamızın sonuçları artmış oksidatif hasarın kanser hastalarında bu moleküllerin düzeylerini değiştirdiğini öne sürmüştür

Anahtar Kelimeler:

Oksidatif stres, nitrozatif stres, küçük hücreli olmayan akciğer kanseri, meme kanseri

EGF and TNF-a levels and oxidative/ nitrosative stress in breast and non-small cell lung cancer patients

Malignant cells exhibit increased levels of intracellular reactive oxygen species ROS and altered levels of antioxidant molecules. The aim of this study was to evaluate the serum levels of some antioxidants, pro- ducts of lipid peroxidation and protein oxidation, growth factor and cytokine in the serum of breast and non- small cell lung cancer patients. This study includes 20 patients with breast cancer, 20 patients with non-small cell lung cancer and 20 healty subjects with no cancer as controls. Superoxide dismutase SOD , glutathione GSH , nitric oxide NO , malonyldialdehyde MDA , advanced oxidation protein product AOPP , tumor necrosis factor-alpha TNF-a and epidermal growth factor EGF were measured in the serums. Increased levels of lipid peroxidation, protein oxidation and epidermal growth factor; low levels of NO and TNF-a were observed in cancer patients. Elevated GSH concentrations and decreased SOD activities were found in the serum of all the cancer groups. The results of our study suggest that enhanced oxidative damage altered the levels of these molecules in cancer patients.

Keywords:

Oxidative stress, nitrosative stress, non-small cell lung cancer, breast cancer,

PDF

___

1. B. Halliwell, J.M.F. Gutteridge, Free Radicals in biology and medicine, Fourth edition, Oxford University Press, Oxford, UK, 2007.
2. M. Nishikawa, Reactive oxygen species in tumor metastasis, Cancer Lett., 266 (2008) 53.
3. L.F. Dong, V.J. Jameson, D. Tilly, J. Cerny, E. Mahdavian, A. Marín-Hernández, L. HernándezEsquivel, S. Rodríguez-Enríquez, J. Stursa, P.K. Witting, B. Stantic, J. Rohlena, J. Truksa, K. Kluckova, J.C. Dyason, M. Ledvina, B.A. Salvatore, R. MorenoSánchez, M.J. Coster, S.J. Ralph, R.A. Smith, J. Neuzil, Mitochondrial targeting of vitamin E succinate enhances its pro-apoptotic and anticancer activity via mitochondrial complex II, J. Biol. Chem., 286 (2011) 3717.
4. R.J. Sinha, R. Singh, S. Mehrotra, R.K. Singh, Implications of free radicals and antioxidant levels in carcinoma of the breast: A never-ending battle for survival, Indian. J. Cancer., 46 (2009) 146.
5. V. Witko-Sarsat, V. Gausson, A.T. Nguyen, M. Touam, T. Drüeke, F. Santangelo F, B. Descamps-Latscha, AOPP-induced activation of human neutrophil and monocyte oxidative metabolism: a potential target for Nacetylcysteine treatment in dialysis patients, Kidney Int., 64 (2003) 82.
6. L.L. Thomsen, J.M.J. Scott, P. Topley, R.G. Knowles, A.J. Keerie, A.J. Frend, Selective inhibition of inducible nitric oxide synthase inhibits tumour growth in vivo: studies with 1400W, a novel inhibitör, Cancer Res., 57 (1997) 3300.
7. K. Datta, S. Sinha, P. Chattopadhyay, Reactive oxygen species in health and disease, Natl. Med. J. India, 13 (2000) 304.
8. A. Acharya, I. Das, D. Chandhok, T. Saha, Redox regulation in cancer A double-edged sword with therapeutic potential, Oxid .Med. Cell Longev., 3 (2010) 23.
9. T. Yoshioka, K. Kawada, T. Shimada, M. Mori, Lipid peroxidation in maternal and cord blood and protective mechanism against activated-oxygen toxicity in the blood, Am. J. Obstet. Gynecol., 135 (1979) 372.
10. V. Witko-Sarsat, M. Friedlander, K.T. Nguyen, C. Capeillere-Blandin, A.T. Nguyen, S. Canteloup, J.M. Dayer, P. Jungers, T. Drüeke, B. Descamps-Latscha, Advanced oxidation protein products as novel mediators of inflammation and monocyte activation in chronic renal failure, J. Immunol., 161 (1998) 2524.
11. S. Yi-Sun, L.W. Oberley, Y. Li, A Simple Method for Clinical Assay of Superoxide Dismutase, Clin. Chem., 34 (1988), 497.
12. J. Sedlak, R.H. Lindsay, Estimation of total, proteinbound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent, Anal. Biochem., 25 (1968) 192.
13. K.M. Miranda, M.G. Espey, D.A. Wink, A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite, Nitric Oxide, 5 (2001) 62.
14. M. Valko, C.J. Rhodes, J. Moncol, M. Izakovic, M. Mazur, Free radicals, metals and antioxidants in oxidative stress-induced cancer, Chem. Biol. Interact., 160 (2006) 1.
15. M.S. Cooke, M.D. Evans, M. Dizdaroglu, J. Lunec, Oxidative DNA damage: mechanisms, mutation and disease, Faseb J., 17 (2003) 1195.
16. L.J. Marnett, Oxyradicals and DNA damage, Carcinogenesis, 21 (2000) 361.
17. M. Thangaraju, T. Vijayalakshmi, P. Sachdanandam P, Effect of tamoxifen on lipid peroxide and antioxidative system in postmenopausal women with breast cancer, Cancer, 74 (1994) 78.
18. O. Portakal, O. Ozkaya, M. Erden Inal, B. Bozan, M. Kosan, I. Sayek, Coenzyme Q10 concentrations and antioxidant status in tissues of breast cancer patients, Clin. Biochem., 33 (2000) 279.
19. A. Gupta, S. Srivastava, R. Prasad, S.M. Natu, B. Mittal, M.P. Negi MP, A.N. Srivastava, Oxidative stress in nonsmall cell lung cancer patients after chemotherapy: association with treatment response, Respirology, 15 (2010) 349.
20. S. Tamir, S.R. Tannenbaum, The role of nitric oxide (NO.) in the carcinogenic process, Biochim. Biophys. Acta, 1288 (1996) 31.
21. M. Zieba, D. Nowak, M. Suwalski, G. Piasecka, I. Grzelewska-Rzymowska, K. Tymi ska, J. Kroczy skaBednarek, S. Kwiatkowska, Enhanced lipid peroxidationin cancer tissue homogenates in nonsmall cell lung cancer, Monaldi Arch. Chest. Dis., 56 (2001) 110.
22. E. Skrzydlewska, A. Stankiewicz, M. Sulkowska, S. Sulkowski, I. Kasacka, Antioxidant status and lipid peroxidation in colorectal cancer, J. Toxicol. Environ. Health., 65 (2001) 213.
23. C.P. Pajneesh, A. Manimaran, K.R. Sasikala, P. Adaikappan, Lipid peroxidation and antioxidant status in patients with breast cancer, Singapore Med. J., 49 (2008) 640.
24. R. Liu, L.W. Oberley, Transfection and expression of MnSOD cDNA decreases tumor malignancy of human oral squamous carcinoma SCC-25 cells, Hum. Gene Ther., 8 (1997) 585.
25. B. Halliwell, The antioxidant paradox, Lancet., 355 (2000) 1179.
26. A. Gonenc, D. Erten, S. Aslan, M. Akinci, B. Simsek, M. Torun, Lipid peroxidation and antioxidant status in blood and tissue of malignant breast tumor and benign breast disease, Cell Biol. Int., 30 (2006) 376.
27. C.C. Yeh, M.F. Hou, S.M. S.K. Lin, J.K. Hsiao, J.C. Huang, L.H. Wang, S.H. Wu, L.A. Hou, H. Ma, L.Y. Tsai LY, Superoxide anion radical, lipid peroxides and antioxidant status in the blood of patients with breast cancer, Clin. Chim. Acta, 361 (2005) 104.
28. S. Nechuta, W. Lu, Z. Chen, Y. Zheng, K. Gu, H. Cai, W. Zheng, X.O. Shu, Vitamin supplement use during breast cancer treatment and survival: a prospective cohort study, Cancer Epidemiol. Biomarkers Prev., 20 (2011) 262.
29. E. Obrador, J. Navarro, J. Mompo, M. Asensi, J.A. Pellicer, J.M. Estrela, Glutathione and the rate of cellular proliferation determine tumor cell sensitivity to tumor necrosis factor in vivo, Biochem. J., 325 (1997) 183.
30. M. Erhola, M.M. Nieminen, A. Ojala, T. Metsa¨-Ketela¨, P. Kellokumpu-Lehtinen, H. Alho, Human plasma antioxidant capacity during radiotherapy for lung cancer: a clinical study, J. Exp. Clin. Cancer Res., 17 (1998) 325.
31. M. Crohns, S. Saarelainen, H. Kankaanranta, E. Moilanen, H. Alho, P. Kellokumpu-Lehtinen, Local and systemic oxidant/antioxidant status before and during lung cancer radiotherapy, Free Radical Research, 43 (2009) 646.
32. E. Skrzydlewska, A. Stankiewicz, M. Sulkowska, S. Sulkowski, I. Kasacka, Antioxidant status and lipid peroxidation in colorectal cancer. J. Toxicol. Environ. Health, 64 (2001) 213.
33. S. Balasenthil, M. Saroja, C.P. Ramachandran, S. Nagini, Of humans and hamsters: comparative analysis of lipid peroxidation glutathione and glutathionedependent enzymes during oral carcinogenesij.s, Br. J. Oral. Maxillofac. Surg., 38 (2000) 267.
34. C.R. Yang, Y.C. Ou, J.H. Kuo, Y.L. Kao, C.L. Chen, S.Y. Yean, Y.Y. Horng, C.S. Yang, Intracellular glutathione content of urothelial cancer in correlation to chemotherapy response, Cancer Lett 119 (1997) 157.
35. B. Melloni, M.A. Lefebvre, F. Bonnaud, A. Vergnene`gre, L. Grossin, M. Rigaud, A. Cantin, Antioxidant activity in bronchoalveolar lavage fluid from patients with lung cancer, Am. J. Respir. Crit. Care Med., 154 (1996) 1706.
36. S. Chandramathi, K. Suresh, Z.B. Anita, U.R. Kuppusamy, Comparative assessment of urinary oxidative indices in breast and colorectal cancer patients, J. Cancer Res. Clin. Oncol., 135 (2009) 319.
37. P. Tesarová, M. Kalousová, B. Trnková, J. Soukupová, S. Argalásová, O. Mestek, L. Petruzelka, T. Zima, Carbonyl and oxidative stress in patients with breast cancer--is there a relation to the stage of the disease?, Neoplasma, 54 (2007) 219.
38. H.L. Tu, J.X. Xiao, H.B. Sun, L. Zhang, Y. Lin, Y.C. Wei, Role of oxidative stress and thioredoxin in gastric cancer, Nan Fang Yi Ke Da Xue Xue Bao., 31 (2011) 1518.
38. A. Heler, The need for monitoring the actual nitric oxide concentration in tumors, Bioanal Rev., 1 (2009) 3.
39. A. Gonenc¸ D. Erten, S. Aslan, M. Akinci, B. Simsek, M. Torun, Lipid peroxidation and antioxidant status in blood and tissue of malignant breast tumor and benign breast disease, Cell Biol. Int., 30 (2006) 376.
40. A.N. Srivastava, A. Gupta, S. Srivastava, S.M. Natu, B. Mittal, M.P. Negi, R. Prasad, Cisplatin combination chemotherapy induces oxidative stress in advance non small cell lung cancer patients, Asian Pac. J. Cancer Prev., 11 (2010) 465.
41. W. Xu, L.Z. Liu, M. Loizidou, M. Ahmed, I. Charles, The role of nitric oxide in cancer, Cell Research, 12 (2002) 311.
42. S. Wu, C.M. Boyer, R.S. Whitaker, A. Berchuck, J.R. Wiener, J.B. Weinberg, R.C. Jr. Bast, Tumor necrosis factor alpha as an autocrine and paracrine growth factor for ovarian cancer: monokine induction of tumor cell proliferation and tumor necrosis factor alpha expression, Cancer Res., 53 (1993) 1939.
43. R.Y. Liu, C. Fan, G. Liu, N.E. Olashaw, K.S. Zuckerman, Activation of p38 mitogen-activated protein kinase is required for tumor necrosis factor-alpha supported proliferation of leukemia and lymphoma cell lines, J. Biol. Chem., 275 (2000) 21086.
44. R.J. Moore, D.M. Owens, G. Stamp, C. Arnott, F. Burke, N. East, H. Holdsworth, L. Turner, B. Rollins, M. Pasparakis, G. Kollias, F. Balkwill, Mice deficient in tumor necrosis factor-alpha are resistant to skin carcinogenesis, Nat. Med., 5 (1999) 828.
45. M. Suganuma, S. Okabe, M.W. Marino, A. Sakai, E. Sueoka, H. Fujiki, Essential role of tumor necrosis factor alpha (TNF-alpha) in tumor promotion as revealed by TNF-alpha-deficient mice, Cancer Res., 59 (1999) 4516.
46. A. Yamada, N. Saito, S. Kameoka, M. Kobayashi, Clinical significance of epidermal growth factor (EGF) expression in gastric cancer, Hepatogastroenterol., 54 (2007) 1049.