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Role of oxidative stress in the antitumoral action of a new vanadyl(IV) complex with the flavonoid chrysin in two osteoblast cell lines: relationship with the radical scavenger activity

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Abstract

The new complex [VO(chrysin)2EtOH]2 (VOchrys) has been synthesized and thoroughly characterized. Fourier transform IR, UV–vis, diffuse reflectance, and EPR spectroscopies as well as elemental analysis and thermal measurements were performed. In solution, different species could be detected by EPR spectroscopy as a function of the ligand-to-metal ratio. The stoichiometry of the chelate complex formed at pH 5 was also determined by spectrophotometric titrations. Since flavonoids are natural antioxidant compounds, the antioxidant capacity of chrysin and its vanadyl(IV) complex was investigated using different radicals. Chrysin and its complex were not able to diminish the level of superoxide and 1,1-diphenyl-2-picrylhydrazyl radicals to a great extent. In contrast, they were strong scavengers for 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid diammonium salt radical cations and OH· radicals with a greater potency for VOchrys. Taking into account their selective antioxidant properties, we investigated the bioactivity of these compounds in two osteoblast-like cells in culture. Chrysin and VOchrys caused an inhibition of cell proliferation in MC3T3E1 normal osteoblasts and UMR106 tumor cells in a dose-response manner, with a greater effect in the latter cell line. The generation of reactive oxygen species (ROS) was evaluated in both cell lines and a correlation could be established between the antiproliferative effects of chrysin and the increase in the ROS levels. The complex did not generate types of ROS that can be detected by the dihydrorhodamine 123 technique so the antiproliferative effect may be attributed to the formation of other radicals such as superoxide, which is not detected by this probe. The morphological alterations were in agreement with these changes.

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Abbreviations

ABTS:

2,2′-Azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt

DHR123:

Dihydrorhodamine 123

DMEM:

Dulbecco’s modified Eagle’s medium

DMSO:

Dimethyl sulfoxide

DPPH·:

1,1-Diphenyl-2-picrylhydrazyl radical

FBS:

Fetal bovine serum

NBT:

Nitroblue tetrazolium

PBS:

Phosphate-buffered saline

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

TEAC:

Trolox equivalent antioxidant coefficient

VOchrys:

[VO(chrysin)2EtOH]2

References

  1. Rice-Evans CA, Miller NJ, Paganga G (1996) Free Radic Biol Med 20:933–956

    Article  CAS  PubMed  Google Scholar 

  2. Pietta PG (2000) J Nat Prod 63:1035–1042

    Article  CAS  PubMed  Google Scholar 

  3. Lu F, Jo YL, Cassady JM (1992) J Nat Prod 55:357–363

    Google Scholar 

  4. Habtemariam S (1997) J Nat Prod 60:775–778

    Article  CAS  PubMed  Google Scholar 

  5. Sugihara N, Takayuki A, Ohnishi M, Furuno K (1999) Free Radic Biol Med 27:1313–1323

    Article  CAS  PubMed  Google Scholar 

  6. Zheng X, Meng WD, Xu Y-Y, Cao JG, Qinga FL (2003) Bioorg Med Chem Lett 13:881–884

    Article  CAS  PubMed  Google Scholar 

  7. Koc AN, Silici S, Ayangil D, Ferahbas A, Cankay S (2005) Mycoses 48:205–210

    Article  CAS  PubMed  Google Scholar 

  8. Bors W, Heller W, Michel C, Saran M (1990) Methods Enzymol 186:343–355

    Article  CAS  PubMed  Google Scholar 

  9. Cárdenas M, Marder M, Blank VC, Roguin LP (2006) Bioorg Med Chem 14:2966–2971

    Article  PubMed  Google Scholar 

  10. Ansari A (2008) Main Group Chem 7:43–56

    Article  CAS  Google Scholar 

  11. Pusz J, Nitka B, Zielinska A, Wawer I (2000) Microchem J 65:245–253

    Article  CAS  Google Scholar 

  12. Pusz J, Nitka B (1997) Microchem J 56:373–381

    Article  CAS  Google Scholar 

  13. Pusz J, Nitka B, Kopacz S, Korenman YI (2003) Russ J Gen Chem 73:634–637

    Article  CAS  Google Scholar 

  14. Onishi M (1988) Photometric determination of traces of metals, part II, 4th edn. Wiley, New York

    Google Scholar 

  15. Yamaguchi T, Takamura H, Matoba TC, Terao J (1998) Biosci Biotechnol Biochem 62:1201–1204

    Article  CAS  PubMed  Google Scholar 

  16. Pellegrini RN, Proteggente A, Pannala A, Yang M, Rice-Evans C (1999) Free Radic Biol Med 26:1231–1237

    Article  PubMed  Google Scholar 

  17. Gorinstein S, Moncheva S, Katrich E, Toledo F, Arancibia P, Goshev I, Trakhtenberg S (2003) Mar Pollut Bull 46:1317–1325

    Article  CAS  PubMed  Google Scholar 

  18. Kuo CC, Shih M, Kuo Y, Chiang W (2001) J Agric Food Chem 49:1564–1570

    Article  CAS  PubMed  Google Scholar 

  19. Halliwell B, Gutteridge JMC, Aruoma OI (1987) Anal Biochem 165:215–219

    Article  CAS  PubMed  Google Scholar 

  20. Zhong Z, Ji X, Xing R, Liu S, Guo Z, Chen X, Li P (2007) Bioorg Med Chem 15:3775–3782

    Article  CAS  PubMed  Google Scholar 

  21. Cortizo AM, Etcheverry SB (1995) Mol Cell Biochem 145:97–102

    Article  CAS  PubMed  Google Scholar 

  22. Krejsa CM, Nadler SG, Esselstyn JM, Kavanagh TJ, Ledbetter JA, Schieven GL (1997) J Biol Chem 272:11541–11549

    Article  CAS  PubMed  Google Scholar 

  23. Bradford M (1976) Anal Biochem 72:248–254

    Article  CAS  PubMed  Google Scholar 

  24. Sálice VC, Cortizo AM, Gómez Dumm CL, Etcheverry SB (1999) Mol Cell Biochem 198:119–128

    Article  PubMed  Google Scholar 

  25. Engelmann MD, Hutcheson R, Cheng IF (2005) J Agric Food Chem 53:2953–2960

    Article  CAS  PubMed  Google Scholar 

  26. Castro GT, Ferretti FH, Blanco SE (2005) Spectrochim Acta A 62:657–665

    Article  CAS  Google Scholar 

  27. Chasteen ND (1981) Vanadyl (IV) spin probes, inorganic and biochemical aspects. In: Berliner LJ, Reuben J (eds) Biological magnetic resonance, vol 3. Plenum, New York

    Google Scholar 

  28. Chruscinska E, Garribba E, Micera G, Panzanelli A (1999) J Inorg Biochem 75:225–232

    Article  CAS  Google Scholar 

  29. Buglyó P, Kiss E, Fábián I, Kiss T, Sanna D, Garribba E, Micera G (2000) Inorg Chim Acta 306:174–183

    Article  Google Scholar 

  30. Hanson GR, Sun Y, Orvig C (1996) Inorg Chem 35:6507–6512

    Article  CAS  PubMed  Google Scholar 

  31. Amin SS, Cryer K, Zhang B, Dutta SK, Eaton SS, Anderson OP, Miller SM, Reul BA, Brichard SM, Crans DC (2000) Inorg Chem 39:406–416

    Article  CAS  PubMed  Google Scholar 

  32. Stewart CP, Porte AL (1972) J Chem Soc Dalton Trans 1661–1666

  33. Caravan P, Gelmini L, Glover N, Geoffrey Herring F, Li H, McNeill JH, Rettig SJ, Setyawati IA, Shuter E, Sun Y, Tracey AS, Yuen VG, Orvig C (1995) J Am Chem Soc 117:12759–12770

    Article  Google Scholar 

  34. Kiss T, Jakush T, Kilyén M, Kiss E, Lakatos A (2000) Polyhedron 19:2389–2401

    Article  CAS  Google Scholar 

  35. Delgado TC, Tomaz AI, Correia I, Costa Pessoa J, Jones JG, Geraldes CFGC, Margarida M, Castro CA (2005) J Inorg Biochem 99:2328–2339

    Article  CAS  PubMed  Google Scholar 

  36. McPhail DB, Goodman BA (1987) J Chem Soc Faraday Trans 83:3627–3633

    Article  Google Scholar 

  37. Costa Pessoa J, Cavaco I, Correia I, Tomaz I, Duarte T, Matias PM (2000) J Inorg Biochem 80:35–39

    Article  Google Scholar 

  38. Cornman CR, Zovinka EP, Boyajian YD, Geiser-Bush KM, Boyle PD, Sing P (1995) Inorg Chem 34:4213–4219

    Article  CAS  Google Scholar 

  39. Dörnyei A, Marcão S, Costa Pessoa J, Jakusch T, Kiss T (2006) Eur J Inorg Chem 18:3614–3621

    Google Scholar 

  40. Lin-Vien D, Colthup NB, Fateley WG, Grasselli JC (1991) The handbook of infrared and Raman characteristic frequencies of organic molecules. Academic Press, Boston

    Google Scholar 

  41. Nyquist RA (ed) (2001) Interpreting infrared, Raman, and nuclear magnetic resonance spectra, chap 7. Elsevier, Amsterdam

  42. Corredor C, Teslova T, Vega Cañamares M, Chen Z, Zhang J, Lombardi JR, Leona M (2009) Vibr Spectrosc 49:190–195

    Article  CAS  Google Scholar 

  43. Ferrer EG, Salinas MV, Correa MJ, Naso L, Barrio DA, Etcheverry SB, Lezama L, Rojo T, Williams PAM (2006) J Biol Inorg Chem 11:791–801

    Article  CAS  PubMed  Google Scholar 

  44. Etcheverry SB, Ferrer EG, Naso L, Rivadeneira J, Salinas V, Williams PAM (2008) J Biol Inorg Chem 13:435–447

    Article  CAS  PubMed  Google Scholar 

  45. Nuopponena M, Willför S, Jääskeläinen AS, Vuorinen T (2004) Spectrochim Acta A 60:2963–2968

    Article  Google Scholar 

  46. Bencini A, Gatteschi D (1990) EPR of exchange coupled systems. Springer, Berlin

    Google Scholar 

  47. Unamuno I, Gutiérrez-Zorrilla JM, Luque A, Román P, Lezama L, Calvo R, Rojo T (1998) Inorg Chem 37:6452–6460

    Article  CAS  PubMed  Google Scholar 

  48. Harris GK, Willcox JK, Catignani GL (2004) J Food Biochem 28:337–349

    Article  CAS  Google Scholar 

  49. Burda S, Oleszek W (2001) J Agric Food Chem 49:2774–2779

    Article  CAS  PubMed  Google Scholar 

  50. Harman DJ (1956) Gerontology 11:289–300

    Google Scholar 

  51. Warma SD, Devamanoharan PS, Morris SM (1995) Crit Rev Food Sci Nutr 35:111–129

    Article  Google Scholar 

  52. Cos P, Ying L, Calomme M, Hu JP, Cimanga K, Van Poel B, Pieters L, Vlietinck AJ, Vanden Berghe D (1998) J Nat Prod 61:71–76

    Article  CAS  PubMed  Google Scholar 

  53. Yu BP (1994) Physiol Rev 74:139–162

    CAS  PubMed  Google Scholar 

  54. Adams JD, Odunze IN (1991) Free Radic Biol Med 10:161–169

    Article  CAS  PubMed  Google Scholar 

  55. Hall ED (1994) Free radicals in central nervous system injury. In: Rice-Evans C, Burdon RH (eds) Free radical damage and its control. Elsevier, Amsterdam, pp 113–130

    Google Scholar 

  56. Edgington DE (1994) Biotechnology 12:37–39

    Article  CAS  PubMed  Google Scholar 

  57. Ames BN, Shigenaga MK, Hagen TM (1993) Proc Natl Acad Sci USA 90:7915–7922

    Article  CAS  PubMed  Google Scholar 

  58. Halliwell B, Gutteridge JMC (1986) Arch Biochem Biophys 246:501–514

    Article  CAS  PubMed  Google Scholar 

  59. Ko FN, Cheng ZJ, Lin CN, Teng CM (1998) Free Radic Biol Med 25:160–168

    Article  CAS  PubMed  Google Scholar 

  60. Cheng Z, Ren J, Li Y, Chang W, Chen Z (2002) Bioorg Med Chem 10:4067–4073

    Article  CAS  PubMed  Google Scholar 

  61. Das UN, Huang YS, Bēgin ME, Ells G, Horrobin DF (1987) Free Radic Biol Med 3:9–14

    Article  CAS  PubMed  Google Scholar 

  62. Evangelou AM (2002) Crit Rev Oncol Hematol 42:249–265

    Article  PubMed  Google Scholar 

  63. Capella MAM, Capella LS, Valente RC, Gefé M, Lopes AG (2007) Cell Biol Toxicol 23:413–420

    Article  CAS  PubMed  Google Scholar 

  64. Cortizo AM, Bruzzone L, Molinuevo S, Etcheverry S (2000) Toxicology 147:89–99

    Article  CAS  PubMed  Google Scholar 

  65. Schuessel K, Frey C, Jourdan C, Keil U, Weber CC, Müller-Spahn F, Müller WE, Eckert A (2006) Free Radic Biol Med 40:850–862

    Article  CAS  PubMed  Google Scholar 

  66. Masaki H, Sakurai H (1995) Photomed Photobiol 17:121–124

    CAS  Google Scholar 

  67. Qin Y, Lu M, Gong X (2008) Cell Biol Int 32:224–228

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by UNLP, CONICET (PIP1125), ANPCyT (PICT 2008-2218) and CICPBA. E.G.F. and S.B.E. are members of the Carrera del Investigador, CONICET. P.A.M.W. is a member of the Carrera del Investigador CICPBA, Argentina. L.N. is a fellowship holder from CONICET.

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Authors and Affiliations

  1. Facultad de Ciencias Exactas, Centro de Química Inorgánica (CEQUINOR/CONICET, UNLP), Universidad Nacional de La Plata, C. Correo 962, 1900, La Plata, Argentina

    Luciana Naso, Evelina Gloria Ferrer, Susana Beatriz Etcheverry & Patricia Williams

  2. Departamento de Química Inorgánica, Facultad de Ciencia y Tecnología, Universidad del País Vasco, Apdo 644, 48080, Bilbao, Spain

    Luis Lezama & Teófilo Rojo

  3. Cátedra de Bioquímica Patológica, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115, 1900, La Plata, Argentina

    Susana Beatriz Etcheverry

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  1. Luciana Naso
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  2. Evelina Gloria Ferrer
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  6. Patricia Williams
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Correspondence to Patricia Williams.

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Naso, L., Ferrer, E.G., Lezama, L. et al. Role of oxidative stress in the antitumoral action of a new vanadyl(IV) complex with the flavonoid chrysin in two osteoblast cell lines: relationship with the radical scavenger activity. J Biol Inorg Chem 15, 889–902 (2010). https://doi.org/10.1007/s00775-010-0652-z

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