Antiangiogenic Effects of the Apigenin and/or Selenium on Ehrlish Bearing Mice

Azab, Khaled Sh.; Hanafy, Shaden M; El Fateh, Neama M.; Badr, Nermeen M.

doi:10.21608/rjab.2015.53282

Antiangiogenic Effects of the Apigenin and/or Selenium on Ehrlish Bearing Mice

Document Type : Original Article

Authors

¹ Radiation Biology Department, National Center for Radiation Research and Technology, Atomic Energy authority, Cairo, Egypt and Al Farabi Colleage for Dentistry and Nursing, Jeddah, Saudi Arabia.

² Department of Molecular Biology, Genetic Engineering and Biotechnology Research Institute, University of Sadat city-Egypt.

³ Radiation Biology Department, National Center for Radiation Research and Technology, Atomic Energy authority

10.21608/rjab.2015.53282

Abstract

Apigenin, a plant flavenoid compound has been claimed for its antioxidant, anti inflammatory and recently antiangiogenic property. In this paper, the antiangiogenic activity of apigenin and selenium was tested in vitro as well as in vivo via systemic intramuscular injection targeting the improvement of cancer therapeutic protocols. The angiogenic regulators Matrix metalloproteinase 2 and 9( MMP2 and MMP9), the expression of tumor necrosis factor- α (TNF-α; Key cytokine) as well as the antioxidant markers catalase, superoxide dismutase and glutathione peroxidase (CAT, SOD and GPX) and DNA fragmentation were estimated to monitor efficacy of Apigenin and selenium in cancer treatment strategy. All parameters were determined as a time course on days 16 and 22 after tumor volume reached 1mm . The using of MTT assay on Ehrlich ascites carcinoma (EAC) cells in vitro showed that apigenin and /or selenium inhibit EAC cells proliferation. In vivo, Administration of apigenin and /or selenium to mice bearing tumor reduced significantly the TNF-α expression, MMP 2 and 9 levels and nitric oxide (NO) concentration while, increased the liver antioxidant enzymes (CAT, SOD and GPX) activities. The DNA fragmentation and the expression of antiangiogenic factors TIMP- in spleenocytes were significantly increased when compared with their values in mice bearing tumor. From the results obtained, it could be postulated that the synergistic administration of apigenin and selenium might improve the condition of cancer therapy via decreasing the tumor metastasis possibility in addition to increase cancer cells apoptotic transforming factors and conservation of normal cells antioxidant parameters.

References

Badr El-Din, N K. (2004): Protective role of sanumgerman against γ irradiation induced oxidative stress in Ehrlich carcinoma bearing Mice. Nutrition Research, 24 : 271– .

Begum, N.; Prasad, N.G.; Kanimozhia, A.Q. and Hasan, S.(2012): Apigenin ameliorates gamma radiation-induced cytogenetic alterations in cultured human blood lymphocytes . Mutation Research , 747 : 71– .

Birkedal-Hansen, H. and Taylor, R. E. (1982): Detergent activation latent collagenase and resolution of its molecules. Biochem. Biophys. Res. Commun., - .

Bisht, K.; Wagner, K and Bulmer, A.C.(2010): Curcumin, resveratrol and flavonoids as anti-inflammatory cyto- and DNA-protective dietary compounds . Toxicology , : 88–

Caia, J.; Zhao, X.L.; Liua, A.W. and Nian, H .(2011): Apigenin inhibits hepatoma cell growth through alteration of gene expression patterns. Phytomedicine ,18 : 366– .

Feng, Ch.; Med, M. and Wang, H. (2011) : Expression of pigment epithelium-derived factor and tumor necrosis factor-α is correlated in bladder tumor and is related to tumor angiogenesis , Urologic Oncology: Seminars and Original Investigations 6:20- .

Freimoster, F.M.; Jkob, C.A.; Aebi, M. and Tuor, U (1999): The MTT [3, (4,5)-Dimethylthiazol-2-yl) -2, 5 – Diphenyltetrazolium bromide] assay is a fast and reliable method for calorimetric determination of fugal cell densities. Applied and Environmental microbiology 65:3727- .

Research Journal of Applied Biotechnology (RJAB)

Fulda, S. (2009):Tumor resistance to apoptosis. International Journal of Cancer, 124( 3): 511– .

Furukawa, A.; Tsuji, M.; Nishitani, M. and Kagawa , S.(1998): Role of the matrix metalloproteinase and tissue inhipitors of metalloproteinase families in non invasive and invasive tumors transplanted in mice with severe combined immunodeficiency. UROLOGY . 849– .

Ghobrial, I.M.; Witizig, T.E. and Adjei, A.A. (2005): Apoptosis pathways in cancer therapy. CA. Cancer J .Clin.,12:134- .

Gonenc , A.; Ozkan, Y.; Torun, M. and Simsek, B. (2001):Plasma malondialdehyde (MDA) levels in breast and lung cancer patients. J Clin Pharm Ther., 26:141– .

Gross R. T., R. Bracci., et al ( . "Hydrogen Peroxide Toxicity and Detoxification in the Erythrocytes of Newborn Infants." J.Blood ( - .

Hanahan, D. and Folkman, J. (1996) : Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell, 86:353– .

Hanahan, D., Weinberg, R.A. (2000): The hallmarks of cancer, Cell biology, 100 : 57– .

Jayaprakash, V. and Marshall, J.R.(2011): Selenium and other antioxidants for chemoprevention of gastrointestinal cancers. Best Practice & Research Clinical Gastroenterology , 25 : 507– .

Jonathan, C. K.; Qing, Y. L.; Gang , L.and Aune, M.(2012): Evidence for activation of mutated p53 by apigenin in human pancreatic cancer. Biochimica et Biophysica Acta .,1823 : 593– .

Kim, J .E.; Kwon , J.Y. and Joo Lee, H.(2009): MKK4 is a novel target for the inhibition of tumor necrosis factor-α induced vascular endothelial growth factor expression by myricetin . biochemical pharmacology, 7 7 : 41 2 –

Kralova, V.; Benešova, S.; Ervinka, M.C. and Rudolf, E.(2012): Selenite -induced apoptosis and autophagy in colon cancer cells. Toxicology in Vitro, 26 : 258–

kumar, P. P .and Kuttan, G.(2011): Nomilin inhibits tumor-specific angiogenesis by downregulating VEGF, NO and proinflammatory cytokine profile and also by inhibiting the activation of MMP-2 and MMP- . European Journal of Pharmacology ,668 : 450– .

Liping, F.; Liu, Q.; Shen, L. and Wang, Y.(2011): Proteomic study on sodium selenite-induced apoptosis of human cervical cancerHeLa cells . Journal of Trace Elements in Medicine and Biology, 25 : 130– .

Liu, J.G.; Zhao, H.J.; Yan-Juan, L. and , Wang , X.L.(2010): Effect of selenium-enriched malt on VEGF and several relevant angiogenic cytokines in diethylnitrosamine –induced hepato carcinoma rats . Journal of Trace Elements in Medicine and Biology, 24 : 52– .

Mandy, D.; Diesel,B.; Martin C.H.and Gruhlke, U.(2012): Selenium- and tellurium-containing redox modulators with distinct activity against macrophages: possible implications for the treatmentof inflammatory diseases,.Tetrahedron ,30 : 1- .

Manoharan, S.; Kavitha, K.; Senthil, N.and Renju, G.L.(2006): Evaluation of anticarcinogenic effects of Clerodendron inerme on 7,12-

Research Journal of Applied Biotechnology (RJAB)

dimethylbenz(a)anthracene-induced hamster buccal pouch carcinogenesis. Singapore Med. J., 47: 1038– .

Mariappan, G.; Sundaraganesan, N. and Manoharan, S.(2012): The spectroscopic properties of anticancer drug Apigenin investigated by using DFT calculations, FT-IR, FT-Raman and NMR analysis . Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 95 : 86– .

Mehmet, S.; Emel, S. and Gümüs¸ S. (2012): Effects of lycopene and apigenin on human umbilical vein endothelial cells in vitro under angiogenic stimulation. Acta Histochemica., 114 : 94– .

Minami M and H. Yoshikawa (1979). "A simplified assay method of superoxide dismutase activity for clinical use." Clin Chim Acta ( - .

Miranda, K.M., Espey, M.G. and Wink, D.A. (2001): A rapid simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide 5: 67– .

Mortensen, K. ; Lichtenberg, J and Thomsen, P.D. (2004) : Spontaneous fusion between cancer cells and endothelial cells . Cell. Mol. Life Sci., 61 : 2125– .

Nahid, S.W.; Murphy, B .J.and Nurulain T. Z. (2010): Increase in tissue inhibitor of metalloproteinase-2 (TIMP-2) levels and inhibition of MMP-2 activity in a metastatic breast cancer cell line by an anti-invasive small molecule SR13179. Cancer Letters , 289 :111– .

Noorizi, M.; Angerson, W.J.and Lean, M.E.J. (1998): Effects of flavonoids and vitamin on oxidative DNA damage to human lymphocyte. Am J Clin Nutr, 67: 1210– .

Papadopoulos, D.; Kimler, B.F.; Estes, N.C. and Durham, F.J. (1989): Growth delay effect of combined interstitial hyperthermia and branchytherapy in a rat solid tumor model. Anticancer Res.9:45- .

Poirier , K.A. and Milner, J.A.(1983) : Factors Influencing the Antitumorigenic Properties of Selenium in Mice , Institute of Nutrition - .

Qiu , L.; Yoshida , K.; Amorim, P.A. and Okamura, H.(2007): Calyculin A stimulates the expression of TNF-α mRNA via phosphorylation of Akt in mouse osteoblastic MC3T3-E1 cells, Molecular and Cellular Endocrinology 271 (2007) 38– .

Sahu, S.K.; Oberley, L.W.; Stevens, R.H.and Riley, E.F.(1977): Superoxide dismutase activity of Ehrlich ascities tumor cells. J Natl Cancer Inst .,58:1125– .

Sang, K. H.; Lee, P.and Jeong , A. P.(2008): Apigenin inhibits the production of NO and PGE2 in microglia and inhibits neuronal cell death in a middle cerebral artery occlusion-induced focal ischemia mice model. Neurochemistry International , 52 : 878– .

Sellins, K.S. and Cohen, J.J (1987): Gene induction by γ-irradiation leads to DNA fragmentation in lymphocytes. J. Immonol.139:3199- .

Research Journal of Applied Biotechnology (RJAB)

Selvaraj, V.; Tomblin, J.; Armistead, M.Y. and Murray, E.(2013): Selenium (sodium selenite) causes cytotoxicity and apoptotic mediated cell death in PLHC-1 fish cell line through DNA and mitochondrial membrane potential damage. Ecotoxicology and Environmental Safety, 87 : 80– .

Silvan, S. and Manoharan, Sh.(2012): Apigenin prevents deregulation in the expression pattern of cell-proliferative, apoptotic, inflammatory and angiogenic markers during 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis. Archives of oral biology, 30 :35– .

Singh, P.V.; Selvendiran, K.; Mumtaz Banu, S.; Padmavathi, R. and Sakthisekaran, D.(2004): Protective role of Apigenin on the status of lipid peroxidation and antioxidant defense against hepatocarcinogenesis in Wistar albino rats. Phytomedicine , 11: 309– .

Sinha A. K (1972). "Colorimetric assay of catalase." J.Anal Biochem ( - .

Song , K. F.; Zhang , H.and junShang, Z.(2012): Tumor necrosisfactor- α enhanced fusions between oral squamous cell carcinoma cells and endothelial cells via VCAM-1/VLA-4pathway . Experimental cell research,3 1 8 :1707–

Wang, H.; Wei, W.; Zhang, S.; Shen, Y., Yue L.; Wang N.and Xu, H. ( Melatonin-selenium nanoparticles inhibit oxidative stress and protect against hepatic injury induced by Bacillus Calmette–Guérin/ lipopolysaccharide in mice. J. Pineal Research., 39: 156– .

Xu, W.; Liu, L.Z.; Loizidou, M. and Ahmed, M. (2002): The role of nitric oxide in cancer. Cell Res. ,12(5- - .

Yamagata, K.; Miyashita, A.; Chino, M. and Matsufuji, H.(2011) : Apigenin inhibits tumor necrosis factor alpha plus high glucose-induced LOX- expression in human endothelial cells. Microvascular Research ,81 : 60– .

Yang, K.; Tagawa, Ch; Matsufuji, H. and Chino, M.(2012): Dietary apigenin regulates high glucose and hypoxic reoxygenation-induced reductions in apelin expression in human endothelial cells. Journal of Nutritional Biochemistry , 23 : 929–

Yhee, J. Y.; Yu, C. H. ;. Kim, J. H. and Brodersen, B.W.(2012):Angiogenesis and Expression of Vascular Endothelial Growth Factor, Tumour Necrosis Factor-α and Hypoxia Inducible Factor-1 in Canine Renal Cell Carcinoma . J. Comp. Path. , 147: 129- .

Zhang, F.; Wei , Y.; James, L. and Hargrove, P.(2002): Inhibition of TNF-α induced ICAM-1, VCAM-1 and E-selectin expression by selenium, Atherosclerosis 161 : 381– .