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In vitro andin vivo antineoplastic effects of ortrovanadate

  • Part II: Biochemical and Physiological Studies
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Abstract

In the present study we have demonstrated that orthovanadate at concentrations of 5–10 uM is cytotoxic to proliferating cells including primary cultures and tumour cell lines. However, concentrations of up to 50 uM did not affect the viability of non-proliferating cells. The cytotoxicity appears to be dependent on the vanadium concentration rather than on the oxidation state of vanadium or the vanadium compound. Furthermore, tumour cell lines with different proliferative rates were equally sensitive to orthovanadate cytotoxicity. Although the mechanisms responsible for the cytotoxicity are not known, addition of H2O2 potentiated orthovanadate cytotoxicity suggesting that hydroxyl or vanadium radicals may be involved.In vivo subcutaneous injections of orthovanadate into mice containing MDAY-D2 tumours resulted in the inhibition of tumour growth by 85–100%. These data indicated that orthovanadate at concentrations greater than 5 uM has antineoplastic properties and may be useful as a chemotherapeutic agent.

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References

  1. Shechter Y: Perspective in diabetes: insulin-mimetic effects of vanadate, possible implications for future treatment of diabetes. Diabetes 39: 1–5, 1990

    Google Scholar 

  2. Meyerovitch J, Farfel Z, Sack J, Schechter Y: Oral administration of vanadate normalizes blood glucose levels in streptozotocin-treated rats: characterization and model of action. J Biol Chem 262: 6658–6662, 1987

    Google Scholar 

  3. D'Onorfio F, Le MQU, Chiasson J-L, Srivastava AK: Activation of mitogenm. FEBS Lett 340: 269–275, 1994

    Google Scholar 

  4. Conquer JA, Grima DT, Cruz TF: Orthovanadate inhibits interleukin-1 and phorbol ester induced collagenase production by chondrocytes. Ann New York Acad Sci 732: 447–450, 1994

    Google Scholar 

  5. Stern A, Yin X, Tsang SS, Davison A, Moon J: Vanadium as a modulator of cellular regulatory cascades and oncogene expression. Biochem Cell Biol 71: 103–112, 1993

    Google Scholar 

  6. Swarup G, Cohen S, Garbers DL: Inhibition of membrane phosphotyrosyl-protein phosphatase activity by vanadate. Biochem Biophys Res Commun 107: 1104–1109, 1982

    Google Scholar 

  7. Gordon JA: Use of vanadate as protein-phosphotyrosine phosphatase inhibitor. Enzymol 201: 477–482, 1990

    Google Scholar 

  8. Afshari CA, Kodama S, Bivins HM, Willard TB, Fujiki H, Barrett JC: Induction of Neoplastic Progression in syrian hamster embryo cells treated with protein phosphatase inhibitors. Cancer Res 53: 1777–1782, 1993

    Google Scholar 

  9. Rijksen G, Voller MCW, Van Zoelen EJJ: Orthovanadate both mimics and antagonizes the transforming GrowthB action on normal rat kidney cell. J Cell Physiol 514: 393–401, 1993

    Google Scholar 

  10. Thompson H, Chasteen ND, Mroker LD: Dietary vanadyl(IV) sulfate inhibits chemically-induced mammary carcinogenesis. Carcinogenesis 5: 849–851, 1984

    Google Scholar 

  11. Ravi Shankar HN, Ramasarma T: Multiple reaction in vanadyl-V (IV) oxidation by H2O2. Mol Cell Biochem 129: 9–29, 1993

    Google Scholar 

  12. Shi X, Dalal NS: Hydroxyl radical generation in the DADH/microsomal reduction of vanadate. Free Rad Res Comms 17: 369–376, 1992

    Google Scholar 

  13. Cruz TF, Mills G, Prikker PH, Kandel AK: Inverse correlation between tyrosine phosphorylation and collagenase production in chondrocytes. Biochem J 269: 717–721, 1990

    Google Scholar 

  14. Akiyama S, Fojo A, Hanover JA, Pastan I, Gottesman MM: Isolation and genetic characterization of human KB cell lines resistant to multiple drugs. Somatic Cell Mol Genetics 11: 117–126, 1985

    Google Scholar 

  15. Barry MA, Beehnke CA, Eastman A: Activation of programmed cell death (Apoptosis) by cisplatin, other anticancer drugs, toxins and hyperthermia. Biochem Pharmacol 40: 2353–2362, 1990

    Google Scholar 

  16. Dive C, Hickman JA: Drug target interactions: only the first step in the commitment to a programmed cell death? Br J Cancer 64: 192–196, 1991

    Google Scholar 

  17. Kovach JS, Svingen PA, Schaid DJ: Levamisole potentiation of fluorouracil antiproliferative activity mimicked by orthovanadate, an inhibitor of tyrosine phosphatase. J National Cancer Inst 84: 515–519, 1992

    Google Scholar 

  18. Grima DT, Kandel RA, Pepinsky B, Cruz TF: Lipocortin 2 (Annexin 2) is a major substrate for constitutive tyrosine kinase activity in chondrocytes. Biochemistry 33: 2921–2926, 1994

    Google Scholar 

  19. Younes M, Strubelt O: Vanadate-induced toxicity towards isolated perfused rat livers: the role of lipid peroxidation. Toxicology 66: 63–74, 1991

    Google Scholar 

  20. Stacey NH, Kappus H: Comparison of methods of assessment of metal-induced lipid peroxidation in isolated rat hepatocytes. J Toxicol Environ Health 9: 277–284, 1982

    Google Scholar 

  21. Oberley LW, Buettner GR: Role of superoxide dismutase in cancer: a review. Cancer Res 39: 1141–1149, 1979

    Google Scholar 

  22. Sun Y: Free radicals, antioxidant enzymes and carcinogenesis. Free Rad Biol Med 8: 583–599, 1990

    Google Scholar 

  23. Zaporowska H, Wasilewski W, Stotwinska M: Effect of chronic vanadium administration in drinking water to rats. Biometals 6: 3–10, 1992

    Google Scholar 

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Cruz, T.F., Morgan, A. & Min, W. In vitro andin vivo antineoplastic effects of ortrovanadate. Mol Cell Biochem 153, 161–166 (1995). https://doi.org/10.1007/BF01075933

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  • DOI: https://doi.org/10.1007/BF01075933

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