The development of new and effective antitumor agents is one of the main goals of medicinal and biochemical research at present. The present study is concerned with the evaluation of the previously synthesized N-Butylpyridoquinoxaline 1,4-dioxide (NBPQD) as an antitumor agent against Ehrlich ascites carcinoma (EAC). The first part of the study (tumor imaging) was to investigate the biodistribution of NBPQD in the organs of EAC-bearing mice using iodine-125 isotope stressing on its distribution in the main organs (stomach, liver, spleen, kidney) in addition to blood and ascetic fluid. The second part was the assessment of the antitumor activity of NBPQD by estimating the tumor volume and the contents of total protein, total lipid, DNA and RNA in liver tissues. In addition, liver function tests and the redox status were assessed. Tumor volume and DNA, RNA, urea and malondialdehyde (MDA) levels and the liver enzymes activity were highly significantly increased (P < 0.001) in untreated EAC-bearing mice compared to control. However, total lipid and total protein in liver tissues in addition to serum albumin, glucose, reduced glutathione (GSH) as well as activities of glutathione reductase (GSH-R) and superoxide dismutase (SOD) all were highly significantly decreased in untreated EAC-bearing mice compared to controls. All these decreased parameters were highly significantly restored to their normal levels in NBPQD treated mice compared to the untreated EAC-bearing mice. The survival time of the NBPQD treated mice was longer than that of the untreated ones. It is thus, evident that NBPQD had a remarkable antitumor activity against EAC in Swiss albino mice.
Boulanger, C.A., Wagner, K.U. and Smith, G.H. (2005) Parity-induced mouse mammary epithelial cells are pluripotent, self-renewing and sensitive to TGFb1 expression. Oncogene, 24, 552-556. doi:10.1038/sj.onc.1208185
Shipitsin, M., Campbell, L.L., Argani, P., Weremowicz, S., et al. (2007) Molecular definition of breast tumor heterogeneity. Cancer Cell, 11, 259-273. doi:10.1016/j.ccr.2007.01.013
Azad, N., Rojanasakul, Y. and Vallyathan, V. (2008) Inflammation and lung cancer: Roles of reactive oxygen/ nitrogen species. Journal of Toxicology and Environmental Health, Part B: Critical Reviews, 11, 1-15. doi:10.1080/10937400701436460
Abdal Dayem, A., Choi, H.Y., Kim, J.H. and Ssang, C.G. (2010) Role of oxidative stress in stem, cancer, and cancer stem cells. Cancers, 2, 859-884. doi:10.3390/cancers2020859
Poli, G., Biasi, F. and Chiarpotto, E. (2004) Oxidative stress and cell signaling. Current Medicinal Chemistry, 11, 1163-1182. doi:10.2174/0929867043365323
Naidu, M.S.K., Suryakar, A.N., Swami, S.C., Katkam, R.V. and Kumbar, K.M. (2007) Oxidative stress and antioxidant status in cervical cancer patients. Indian Journal of Clinical Biochemistry, 22, 140-144. doi:10.1007/BF02913333
El-Wahab, S.M.A. and Fouda, F.M. (2009) Histological and histochemical study on the effect of Ehrlich ascites carcinoma on the liver and kidney of mice and the possible protective role of tetrodotoxin. Egyptian Journal of Biology, 11, 13-25.
Ganapathy, S., Ramalingam, P. and Babu Rao, C.H. (2007) Antibacterial, antifungal and antitubercular screening of some novel condensed bridgehead nitrogen heterocycles of quinoxalines. Indian Journal of Heterocyclic Chemistry, 16, 283-286.
Carta, A., Corona, P. and Loriga, M. (2005) Quinoxaline 1,4-dioxide: A versatile scaffold endowed with manifold activities. Current Medicinal Chemistry, 12, 2259-2272. doi:10.2174/0929867054864831
Gali-Muhtasib, H.U., Haddadin, M.J., Rahhal, D.N. and Younes, I.H. (2001) Quinoxaline 1,4-dioxides as anticancer and hypoxia-selective drugs. Oncology Reports, 8, 679- 684.
Xiao, W.H., Dupertuis, Y.M., Mermillod, B., Sun, L.Q., de Tribolet, N. and Buchegger, F. (2000) Unlabeled iododeoxyuridine increases the cytotoxicity and incorporation of iodine-[125] iododeoxyuridine in two human glioblastoma cell lines. Nuclear Medicine Communications, 21, 947-953. doi:10.1097/00006231-200010000-00009
Kassis, A.I., Sastry, K.S.R and Adelestein, S.J. (1987) Kinetics of uptake, retension, and radiotoxicity of 125 IUDR in mmamlian cells: Implications of localised energy depostion by Auger processes. Radiation Research, 109, 78-89. doi:10.2307/3576869
Dupertuis, Y.M., Buchegger, F. and Pichard, C.B.P. (2003) Deoxyribonucleoside mixture increased the rate of DNA incorporation of 5-[125I]iodo-2’-deoxyuridine in glioblastoma cells. Cancer Biotherapy & Radiopharmacuticals, 18, 7-16. doi:10.1089/108497803321269287
Moerlein, S.M., Beer, W. and Stocklin, G. (1988) No Carrier added radio bromination and radioiodoination of aromate rings using in situ, generated peracetic acid. Journal of the Chemical Society, Perkin Transactions, 1, 779-786. doi:10.1039/p19880000779
Brown, J.M. and Koong, A.J. (1999) Therapeutic advantage of hypoxic cells in tumors: A theoritacal study. Journal of the National Cancer Institute, 83, 178-185. doi:10.1093/jnci/83.3.178
Ibrahim, I.T. and Wally, M.A. (2009) Synthesis, labeling and biodistribution of 99mTc-3-amino-2-quinoxalin-carbonitrile 1,4-dioxide in tumor bearing mice. Journal of Radioanalytical and Nuclear Chemistry, 285, 169-175. doi:10.1007/s10967-009-0039-1
Zarranz, B., Jaso, A., Aldana, I. and Monge, A.B. (2004) Synthesis and anticancer activity evaluation of new 2-alkylcarbonyl and 2-benzoyl-3-trifluoromethyl-quinoxaline 1,4-di-N-oxide derivatives. Medicinal Chemistry, 12, 3711-3721. doi:10.1016/j.bmc.2004.04.013
Coenen, S.M., Moerlein, Stocklin G. (1983) No-carreiradded radiohalogenation methods with heavy halogens. Biochimica Acta, 34, 47-68.
Zahran, R.F. (2009) Biochemical studies on the inhibitory effects of some plant extracts on the growth of Ehrlish ascites carcinoma on mice. M.D. Thesis, Damitta University, Damitta.
Jaganathan, S.K., Mondhe, D., Wani, Z.A., Pal, H.C. and Mandal, M. (2010) Effect of honey and eugenol on herlich ascites and solid carcinoma. Journal of Biomedicine and Biotechnology, 989163.
Gupta, M., Mazumder, U.K., Rath, N. and Mukhopadhyay, D.K. (2000) Antitumor activity of methanolic extract of Cassia fistula L. seed against Ehrlich ascites carcinoma. Journal of Ethnopharmacology, 72, 151-156. doi:10.1016/S0378-8741(00)00227-0
Lowry, O.M., Rosebrough, N.J., Farr, A.L. and Randall, R.J. (1951) Protein measurements with the Folin-phenol reagent. Journal of Biological Chemistry, 193, 265-275.
Schneider, W., Hogeboom, G. and Ross, H. (1950) Intracellular distribution of enzymes and nucleic acid in normal mouse liver and mouse hepatoma. Journal of the National Cancer Institute, 10, 977-980.
Dische, Z. and Schwartez, K. (1937) Microchemical Methods for determining various pentoses in the presence of one anotherand of hexoses. Mikrochim Acta, 2, 13-19. doi:10.1007/BF01471868
Mejbaum, W. (1939) Estimation of small amount of pentose especially in derives of adenylic acid. Z Physiol Chem, 258, 117-120. doi:10.1515/bchm2.1939.258.2-3.117
Littelfield, L.W., Keller, E.B., Gress, J. and Zamecnick, P.C.J. (1955) Studies on cytoplasmic ribonucleoprotein particles from liver of the rate. Journal of Biological Chemistry, 217, 111-117.
Knight, J.A., Anderson, S. and Rawle, J.M. (1972) Chemical basis of the sulfophospho-vanilin reaction of estimating total lipids. Journal of Clinical Chemistry, 18, 199-203.
Triner, P. (1969) Determination of blood glucose using an oxidase peroxidase system with non-carcinogenic chromogen. Annals of Clinical Biochemistry, 6, 24-30.
Reitman, S. and Frankel, S. (1957) Determination of serum glutamic oxaloacetic and glutamic pyruvic transaminases. American Journal of Clinical Pathology, 28, 56- 61.
Doumas, B.T., Watson, W.A. and Biggs, H.G. (1971) Albumin standards and the measurement of serum albumin with bromocresol green. Clinica Chimica Acta, 31, 87-93. doi:10.1016/0009-8981(71)90365-2
Beutler, E., Duron, O. and Kelly, B. (1963) Improved method for the determination of blood glutathione. Journal of Laboratory and Clinical Medicine, 61, 882- 890.
Ohkawa, H., Ohish, N. and Yagi, K. (1979) Assay for lipid peroxidase in animal tissues by thiobarbituricacid reaction. Analytical Biochemistry, 95, 351-358. doi:10.1016/0003-2697(79)90738-3
Nishikimi, M., Roa, N.A. and Yogi, K. (1972) The occurrence of superoxide anion in the reaction of reduced phenazine methosulfate and molecular oxygen. Biochemical and Biophysical Research Communications, 46, 849-854. doi:10.1016/S0006-291X(72)80218-3
Drabkin, D.L. and Austin, J.H. (1932) Spectrophotometric constants for common haemoglobin derivatives in human, dog and rabbit blood. Journal of Biological Chemistry, 98, 719-733.
Leammli, U.K. (1970) Cleavge of structural proteins during the assembly of the head of bacteriophage T4. Nature, 227, 680-685. doi:10.1038/227680a0
Sumanta, K.S., Swatilekha, M., Tapas, K.M., Sudip, K.G. and Panchanan, P. (2011) Hydrophobically modified carboxymethyl chitosan nanoparticles targeted delivery of paclitaxel. Journal of Drug Targeting, 19, 104-113. doi:10.3109/10611861003733987
Unak, T. and Unak, P. (1966) Direct radioiodination of metabolic 8-hydroxy-quinolyl-glucuronide, as a potential anti-cancer drug. Applied Radiation and Isotopes, 47, 645-647. doi:10.1016/0969-8043(95)00333-9
Mannan, R.H., Somayaji, V.V., Lee, J., Mercer, J.R. and Weibe, L.I. (1991) Radiiodinated 1-(5-iodo-5-deoxy-β-Darabinofuranosyl)-2-nitroimidazole (Iodoazamycin Arabinoside: IAZA): A novel marker of tissue hypoxia. Journal of Nuclear Medicine, 32, 1764.
Subramanian, V. and Gowry, S. (2011) Antitumor activeity and antioxidant role of Brassica oleracea Italica against ehrlich ascites carcinoma in swiss albino mice. Research Journal of Pharmaceutical, Biological and Chemical Sciences, 2, 275-285.
EL-Sayd, I.H. (1998) Effect of some complexes on tumor-bearing animals. Ph.D. Thesis, Mansoura University, Mansoura, 7.
Devaki, M., Nirupama, R. and Yajurvedi, H.N. (2011) Reduced antioxidant status for prolonged period due to repeated stress exposure in rat. Journal of Stress Physiology & Biochemistry, 7, 13 -147.
Fouda, F.M. (2005) Anti-tumor activity of tetrodotoxin extracted from the Masked Puffer fish Arothron diadematus. Egyptian Journal of Biology, 7, 1-13.
Farag, A.A.M. and Abdel Dayem, S.M. (2001) Biochemical, histological and ultrastructural studies on the protective effect of vitamin A against carcinogenic effect of 7, 12-DMBA on the liver of albino rat. Egyptian Journal of Zoology, 37, 335-368.
Badr, M.O.T., Edrees, N.M.M., Abdallah, A.A.M., Hashem, M.A., El-Deen, N.A.M.N., Neamat-Allah, A.N.F. and Ismail, H.T.H. (2011) Propolis protects against methotrexate induced hepatorenal dysfunctions during treatment of ehrlich carcinoma. Journal of American Science, 7, 313-319.
Gupta, A., Mazumder, U.K., Kumar, R.S. and Kumar, T.S. (2004) Anti-tumor activity and anti-oxident role of Bauhinia racemosa against Ehrlich ascites carcinoma in Swiss albino mice. Acta Pharmacologica Sinica, 25, 1070-1076.