Antioxidant properties of vanadium complexes and their anticancer effects on human gastric cancer cell line MKN45

authors:

avatar Maedeh Dejamfekr , avatar Ali khaleghian ORCID , *


how to cite: Dejamfekr M, khaleghian A. Antioxidant properties of vanadium complexes and their anticancer effects on human gastric cancer cell line MKN45. koomesh. 2019;21(2):e153076. 

Abstract

Introduction: Gastric cancer is the fourth most common cancer worldwide and the second leading cause of death from cancer. In recent years, advances in cancer therapy have raised the specter of developing effective agents of high-impact diseases, like gastric cancer, which remains one of the major causes of cancer deaths in the world. Recently it has been demonstrated that vanadium compounds exhibit a wide variety of pharmacological properties in humans. Vanadium compounds show interesting biological and pharmacological properties and some of them display antitumoral actions. However, the mechanism of action of vanadium compounds in the inhibition of cancer cell proliferation is still elusive. Materials and Methods: In this study, the antioxidant properties of the vanadium compounds were evaluated by two in vitro tests: Ferric reducing ability of plasma (FRP) and 2,2-diphenyl-1-picryl-hydrate (DPPH) radical scavenging. The toxicity of vanadium compounds on cancer cells MKN45 (a gastric cancer cell line) was investigated by using the test MTT in various concentrations of 1, 10, 50, 100, and 500 μg/ml. The percentage of apoptotic cells, after these treatments were investigated using Acridine orange/ Ethidium bromide staining. Wound healing and morphological modification were performed in vitro to examine migration and adhesion in the gastric cancer cell line by invert microscopy. Results: The assessments with DPPH and FRAP techniques showed that vanadium compounds have antioxidant activities. Data showed with an increasing concentration of vanadium compounds the percentage of remaining living cells of MKN45 significantly decreased (P˂0.05). All vanadium compounds showed considerable cytotoxic activity against cancer cell lines (IC50 = 1 μg/ml). The apoptosis investigations showed that vanadium compounds can induce high percentage of apoptosis in a dose of 1 μg/ml. The apoptotic inducing effect of vanadium compounds were confirmed by morphological observation. Migration studies revealed that vanadium compounds have inhibitory effect against the metastatic potency of MKN45 cancer cell lines. Conclusion: The results of this study showed that the vanadium compounds had high cytotoxic effect on gastric cancer cells (MKN45) and the percentage of lethality, with the passage of time and with increased concentration had risen.

References

  • 1.

    Parkin DM, Bray FI, Devesa SS. Cancer burden in the year 2000. The global picture. Eur J Cancer 2001; 37:S4-66.

  • 2.

    Lee MS, Lee JH, Park DJ, Lee HJ, Kim HH, Yang HK. Comparison of short- and long-term outcomes of laparoscopic-assisted total gastrectomy and open total gastrectomy in gastric cancer patients. Surg Endosc 2013; 27:2598-2605.

  • 3.

    Yada T, Yokoi C, Uemura N. The current state of diagnosis and treatment for early gastric cancer. Diagn Ther Endosc2013;2013:241320.

  • 4.

    Takimoto CH, Calvo E. Principles of oncologic pharmacotherapy. Cancer Manag 2008; 11: 1-9.

  • 5.

    Kanna PS, Mahendrakumar CB, Indira BN, Srivastawa S, Kalaiselvi K, Elayaraja T, Chatterjee M. Chemopreventive effects of vanadium toward 1, 2dimethylhydrazineinduced genotoxicity and preneoplastic lesions in rat colon. Environ Mol Mutagen 2004; 44: 113-118.

  • 6.

    Brichard SM, Henquin JC. The role of vanadium in the management of diabetes. Trends Pharmacol Sci1995; 16: 265-270.

  • 7.

    Pessoa JC, Garribba E, Santos MF, Santos-Silva T. Vanadium and proteins: uptake, transport, structure, activity and function. Biochim Biophys Acta 2015; 301: 49-86.

  • 8.

    Tracey AS, Willsky GR, Takeuchi ES. Vanadium: chemistry, biochemistry, pharmacology and practical applications: CRC press; 2007.

  • 9.

    Thompson HJ, Chasteen ND, Meeker LD. Dietary vanadyl(IV) sulfate inhibits chemically-induced mammary carcinogenesis. Carcinogenesis 1984; 5: 849-851.

  • 10.

    Faneca H, Figueiredo VA, Tomaz I, Goncalves G, Avecilla F, Pedroso de Lima MC, Geraldes CF, Pessoa JC, Castro MM. Vanadium compounds as therapeutic agents: some chemical and biochemical studies. J Inorg Biochem 2009; 103: 601-608.

  • 11.

    Lampronti I, Bianchi N, Borgatti M, Fabbri E, Vizziello L, Khan MT, et al. Effects of vanadium complexes on cell growth of human leukemia cells and protein-DNA interactions. Oncol Rep 2005; 14: 9-15.

  • 12.

    Storr T, Mitchell D, Buglyo P, Thompson KH, Yuen VG, McNeill JH, Orvig C. Vanadyl-thiazolidinedione combination agents for diabetes therapy. Bioconjug Chem2003; 14: 212-221.

  • 13.

    Iranmanesh H, Behzad M, Bruno G, Rudbari HA, Nazari H, Mohammadi A, Taheri O. Cobalt (III) Schiff base complexes derived from mesostilbenediamine: Synthesis, characterization, crystal structure, electrochemistry and antibacterial studies, Inorganica Chim. Acta2013; 395: 81-88. (Persian).

  • 14.

    Ray RS, Ghosh B, Rana A, Chatterjee M. Suppression of cell proliferation, induction of apoptosis and cell cycle arrest: Chemopreventive activity of vanadium in vivo and in vitro. Int J Cancer 2007; 120: 13-23.

  • 15.

    Isabel Correia P, Somnath Roy, MohamedWahba, CristinaMatos,MannarR.Maurya, et al. Hydroxyquinoline derived vanadium(IV and V) and copper(II) complexes as potential anti-tuberculosis and anti-tumor agents. J Inorg Biochem 2014; 141: 83-93.

  • 16.

    Nair RS, Kuriakose M, Somasundaram V, Shenoi V, Kurup MR, Srinivas P.The molecular response of vanadium complexes of nicotinoyl hydrazine in cervical cancersA possible interference with HPV oncogenic markers. Life Sci 2014; 116: 90-97.

  • 17.

    Q.-M. Hasi, Y. Fan, X.-Q. Yao, D.-C. Hu, J.-C. Liu, Synthesis, characterization, antioxidant and antimicrobial activities of a bidentate Schiff base ligand and its metal complexes, Polyhedron. 2016; 109: 75-80.

  • 18.

    Oyaizu M. Studies on products of browning reaction. Japanese J Nutr Diet1986; 44: 307-315.

  • 19.

    Garcia-Rodriguez Mdel C, Hernandez-Cortes LM, Altamirano-Lozano MA. In Vivo Effects of Vanadium Pentoxide and Antioxidants (Ascorbic Acid and Alpha-Tocopherol) on Apoptotic, Cytotoxic, and Genotoxic Damage in Peripheral Blood of Mice. Oxid Med Cell Longev 2016; 2016: 6797851.

  • 20.

    Kioseoglou E, Petanidis S, Gabriel C, Salifoglou A. The chemistry and biology of vanadium compounds in cancer therapeutics. Coordinat Chem Rev 2015; 301: 87-105.

  • 21.

    Pessoa JC, Etcheverry S, Gambino D. Vanadium compounds in medicine. Coordinat Chem Rev 2015; 301: 24-48.

  • 22.

    Yilmaz-Ozden T, Kurt-Sirin O, Tunali S, Akev N, Can A, Yanardag R. Ameliorative effect of vanadium on oxidative stress in stomach tissue of diabetic rats. Bosn J Basic Med Sci. 2014; 14: 105-109.

  • 23.

    Liu S, Liu G, Yi Y. Novel vanadyl complexes of alginate saccharides: Synthesis, characterization, and biological activities. Carbohydr Polym2015; 121: 86-91.

  • 24.

    Mazani M, Hadizadeh S, Najafzadeh N, Amani M, Mansouri Torshizi H. Anti-cancer Effects of Palladium Complexes on Gastric Cancer Cell Line (AGS). J Guilan Univ Med Sci 2014; 23: 72-79. (Persian).

  • 25.

    Kooshafar Z, Salimi M, Javid A. Evaluating antitumor effect of a novel hydrazide derivative in mammalian mice model. Koomesh 2018; 20:582-587. (Persian).

  • 26.

    Yarigarravesh M H, Safakhah H A, Rashidi-Pour A, Dehghanian M. Effects of aminoguanidin on the neuropathic behavioral responses of chronic constriction injury model in rat. Koomesh 2009; 10:207-212. (Persian).

  • 27.

    Budisin NI, Majdevac IZ, Budisin ES, Manic D, Patrnogic A, Radovanovic Z. Surgery for patients with gastric cancer in the terminal stage of the illness - TNM stage IV. J BUON 2009; 14:593-603.##.