Antioxidant effects of the VO(IV) hesperidin complex and its role in cancer chemoprevention

  • Susana Beatriz Etcheverry
  • Evelina Gloria Ferrer
  • Luciana Naso
  • Josefina Rivadeneira
  • Victoria Salinas
  • Patricia Ana María Williams
Original Paper

Abstract

Vanadium compounds are known for a variety of pharmacological properties. Many of them display antitumoral and osteogenic effects in several cell lines. Free radicals induce the development of tumoral processes. Natural polyphenols such as flavonoids have antioxidant properties since they scavenge different free radicals. For these reasons it is interesting to investigate the effects of a new complex generated between the vanadyl(IV) cation and the flavonoid hesperidin. The complex has been synthesized and characterized by physicochemical methods. Spectroscopic analysis revealed a 1:1 stoichiometry of ligand:VO and coordination by deprotonated cis-hydroxyl groups to the disaccharide moiety of the ligand. The complex improves the superoxide dismutase (SOD)-like activity of the ligand, but the scavenging of other radicals tested does not change upon complexation. When tested on two tumoral cell lines in culture (one of them derived from a rat osteosarcoma UMR106 and the other from human colon adenocarcinoma Caco-2), the complex enhanced the antiproliferative effects of the free ligand, and this effect correlated with the morphological alterations toward apoptosis. Also, on the osteoblastic cell line the complex stimulated cell proliferation and collagen type I production at low concentrations. At higher doses the complex behaved as a cytotoxic compound for the osteoblasts.

Keywords

Antioxidants Antitumoral Vanadium hesperidin complex Cellular morphology 

Abbreviations

ABTS

2,2′-Azino-bis(3-ethyl-benzothiazoline-6-sulfonic acid diammonium salt)

ALP

Alkaline phosphatase

DMEM

Dulbecco’s modified Eagles medium

DPPH·

1,1-Diphenyl-2-picrylhydrazyl radical

EDTA

Ethylenediaminetetraacetic acid

NADH

Nicotinamide adenine dinucleotide

NBT

Nitroblue tetrazolium

PMS

Phenazine methosulfate

p-NP

p-Nitrophenol

p-NPP

p-Nitrophenylphosphate

SOD

Superoxide dismutase

TEAC

Trolox-equivalent antioxidant coefficient

Trolox

6-Hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid

References

  1. 1.
    Hertog MG, Hollman PC, Katan MB, Kromhout D (1993) Nutr Cancer 20:21–29PubMedCrossRefGoogle Scholar
  2. 2.
    Moridani MY, Pourahmad J, Bui H, Siraki A, O’brien PJ (2003) Free Radic Biol Med 34:243–253PubMedCrossRefGoogle Scholar
  3. 3.
    Kostyuk VA, Potapovich AI, Vladykovskaya EN, Korkina LG, Afanas’ev IBA (2001) Arch Biochem Biophys 385:129–137PubMedCrossRefGoogle Scholar
  4. 4.
    Bors W, Heller W, Michel C, Saran M (1990) Methods Enzymol 186:334–355Google Scholar
  5. 5.
    Peterson J, Dwyer M (1998) Nutr Res 18:1995–2018CrossRefGoogle Scholar
  6. 6.
    Vinson JA, Dabbagh YA, Serry MM, Jang JH (1995) J Agric Food Chem 48:2800–2802CrossRefGoogle Scholar
  7. 7.
    Kostyuk VA, Potapovich AI, Strigunova EN, Kostyuk TV, Afanas’ev IB (2004) Arch Biochem Biophys 428:204–208PubMedCrossRefGoogle Scholar
  8. 8.
    Afanas’ev IB, Ostrakhovitch EA, Mikhal’chik EV, Ibragimova GA, Korkina LG (2001) Biochem Pharmacol 61:677–684CrossRefGoogle Scholar
  9. 9.
    Middleton Jr E, Kandashwami C, Theoharides TC (2000) Pharmacol Rev 52:673–751PubMedGoogle Scholar
  10. 10.
    Ska-Kordala MS, Kowska AB, Ski J, Gabrielska JO (2001) Cell Mol Biol Lett 6:277–281Google Scholar
  11. 11.
    Ferrer EG, Salinas MV, Correa MJ, Naso L, Barrio DA, Etcheverry SB, Lezama L, Rojo T, Williams PAM (2006) J Biol Inorg Chem 11:791–801PubMedCrossRefGoogle Scholar
  12. 12.
    Zhang J, Brodbelt JS, Wang J (2005) J Am Soc Mass Spectrom 16:139–151PubMedCrossRefGoogle Scholar
  13. 13.
    Cos P, Ying L, Calomme M, Hu JP, Cimanga K, Poel BV, Pieters L, Vlietinck AJ, Berghe V (1998) J Nat Prod 61:71–76PubMedCrossRefGoogle Scholar
  14. 14.
    Harborne JB, Williams CA (2000) Phytochemistry 55:481–504PubMedCrossRefGoogle Scholar
  15. 15.
    Garg A, Garg S, Zaneveld LJ, Singla AK (2001) Phytother Res 15:655–669PubMedCrossRefGoogle Scholar
  16. 16.
    Chiba H, Uehara M, Wu J, Wang X, Masuyama R, Suzuki K, Kanazawa K, Ishimi Y (2003) J Nutr 133:1892–1897PubMedGoogle Scholar
  17. 17.
    Miyagi Y, Om AS, Chee KM, Bennink MR (2000) Nutr Cancer 36:224–229PubMedCrossRefGoogle Scholar
  18. 18.
    Kohno H, Taima M, Sumida T, Azuma Y, Ogawa H, Tanaka T (2001) Cancer Lett 174:141–150PubMedCrossRefGoogle Scholar
  19. 19.
    Wilmsen PK, Spada DS, Salvador M (2005) J Agric Food Chem 53:4757–4761PubMedCrossRefGoogle Scholar
  20. 20.
    Nielsen FH (1995) In: Segel H, Sigel A (eds) Metal ions in biological systems, vol 31. Dekker, New York, pp 543–573Google Scholar
  21. 21.
    Slebodnick C, Hamstra BJ, Pecoraro VL (1997) Struct Bonding 89:51–107Google Scholar
  22. 22.
    Crans DC, Smee JJ, Gaidamauskas E, Yang L (2004) Chem Rev 104:949–902CrossRefGoogle Scholar
  23. 23.
    Williams PAM, Etcheverry SB (2007) Oxovanadium(IV) complexes with nonsteroidal antiinflammatory drugs (NSAIDs): pharmacological relevance. In: Aureliano Alves M (ed) Vanadium biochemistry. Research Signpost, India (in press)Google Scholar
  24. 24.
    Heyliger CE, Tahiliani AG, McNeil JH (1985) Science 227:1474–1477PubMedCrossRefGoogle Scholar
  25. 25.
    Shechter Y (1990) Diabetes 39:1–5PubMedCrossRefGoogle Scholar
  26. 26.
    Lampronti I, Bianchi N, Borgatti M, Fabbri E, Vizziello L, Hassan Khan MT, Ather A, Brezena D, Mahroof Tahir M, Gambari R (2005) Oncol Rep 14:9–15PubMedGoogle Scholar
  27. 27.
    Baran EJ (1997) Acta Farm Bonaerense 16:43–52Google Scholar
  28. 28.
    Morinville A, Maysinger D, Shaver A (1998) Trends Pharmacol Sci 19:452–460PubMedCrossRefGoogle Scholar
  29. 29.
    Thompson KH, Orvig C (2001) Coord Chem Rev 219/221:1033–1053CrossRefGoogle Scholar
  30. 30.
    Rehder D (2003) Inorg Chem Commun 6:604–617CrossRefGoogle Scholar
  31. 31.
    Baran EJ (2003) J Braz Chem Soc 14:878–888CrossRefGoogle Scholar
  32. 32.
    Mukherjee B, Patra B, Mahaptra S, Banerjee P, Tiwari A, Chatterjee M (2004) Toxicol Lett 150:135–143PubMedCrossRefGoogle Scholar
  33. 33.
    Beauchamp C, Fridovich I (1971) Anal Biochem 44:276–287PubMedCrossRefGoogle Scholar
  34. 34.
    Iwamoto I, Mifuchi I (1982) Chem Pharm Bull 30:237–241Google Scholar
  35. 35.
    Kuo CC, Shih M, Kuo Y, Chiang W (2001) J Agric Food Chem 49:1654–1570CrossRefGoogle Scholar
  36. 36.
    Yamaguchi T, Takamura H, Matoba TC, Terao J (1998) Biosci Biotechnol Biochem 62:1201–1204PubMedCrossRefGoogle Scholar
  37. 37.
    Pellegrini RN, Proteggente A, Pannala A, Yang M, Rice-Evans C (1999) Free Radic Biol Med 26:1231–1237PubMedCrossRefGoogle Scholar
  38. 38.
    Gorinstein S, Moncheva S, Katrich E, Toledo F, Arancibia P, Goshev I, Trakhtenberg S (2003) Mar Pollut Bull 46:1317–1325PubMedCrossRefGoogle Scholar
  39. 39.
    Okajima T, Nakamura K, Zhang H, Ling N, Tanabe T, Yasuda T, Rozenfeld RG (1992) Endocrinology 130:2201–2212PubMedCrossRefGoogle Scholar
  40. 40.
    Cortizo AM, Etcheverry SB (1995) Mol Cell Biochem 145:97–192PubMedCrossRefGoogle Scholar
  41. 41.
    Onishi M (1988) Photometric determination of traces of metals, part II, 4th edn. Wiley, New YorkGoogle Scholar
  42. 42.
    Etcheverry SB, Crans DC, Keramidas AD, Cortizo AM (1997) Arch Biochem Biophys 338:7–1462PubMedCrossRefGoogle Scholar
  43. 43.
    Stein GS, Lian JB (1993) Endocr Rev 14:424–442PubMedCrossRefGoogle Scholar
  44. 44.
    Bradford M (1976) Anal Biochem 72:248–254PubMedCrossRefGoogle Scholar
  45. 45.
    Tullberg-Reinert H, Jundt G (1999) Histochem Cell Biol 112:271–276PubMedCrossRefGoogle Scholar
  46. 46.
    Sálice VC, Cortizo AM, Gómez Dumm CL, Etcheverry SB (1999) Mol Cell Biochem 198:119–128PubMedCrossRefGoogle Scholar
  47. 47.
    Tommasini S, Calabró ML, Stancanelli R, Donato P, Costa C, Catania S, Villari V, Ficarra P, Ficarra R (2005) J Pharm Biomed Anal 39:572–580PubMedCrossRefGoogle Scholar
  48. 48.
    Hororttz RR, Jurd L (1960) Acric Res Dev 26:2446–2447Google Scholar
  49. 49.
    Zhou J, Wang L, Wang J, Tang N (2001) J Inorg Biochem 83:41–48PubMedCrossRefGoogle Scholar
  50. 50.
    Hartley FR, Burgess C, Alcock RM (1980) Solution equilibria. Ellis Horwood, Chichester, UK, pp 44–45Google Scholar
  51. 51.
    Etcheverry SB, Williams PAM, Baran EJ (1997) Carbohydr Res 302:131–138CrossRefGoogle Scholar
  52. 52.
    Williams PAM, Etcheverry SB, Baran EJ (2000) Carbohydr Res 329:41–47PubMedCrossRefGoogle Scholar
  53. 53.
    Etcheverry SB, Barrio DA, Williams PAM, Baran EJ (2001) Biol Trace Elem Res 84:227–237PubMedCrossRefGoogle Scholar
  54. 54.
    Yang L, Weng S, Ferraro JR, Wu J (2001) Vib Spectrosc 25:57–62CrossRefGoogle Scholar
  55. 55.
    Barrio DA, Williams PAM, Cortizo AM, Etcheverry SB (2003) J Biol Inorg Chem 8:459–468PubMedGoogle Scholar
  56. 56.
    Sreedhara A, Rao CP, Rao BJ (1996) Carbohydr Res 289:39–53PubMedCrossRefGoogle Scholar
  57. 57.
    Weder JE, Dillon CT, Hambley TW, Kennedy BJ, Lay PA, Biffin JR, Regtop HL, Davies NM (2002) Coord Chem Rev 232:95–126CrossRefGoogle Scholar
  58. 58.
    Gärtner A., Weser U (1986) Top Curr Chem 132:1–61CrossRefGoogle Scholar
  59. 59.
    Roberts NA, Robinson PA (1985) Br J Rheumatol 24:128–136PubMedCrossRefGoogle Scholar
  60. 60.
    Rajendran CM, Manisankar P, Gandhidasanm R, Murugesan R (2004) J Agric Food Chem 52:7389–7394PubMedCrossRefGoogle Scholar
  61. 61.
    Barrio DA, Cattáneo ER, Apezteguía MC, Etcheverry SB (2006) Can J Physiol Pharmacol 84:765–775PubMedCrossRefGoogle Scholar
  62. 62.
    Walter E, Kissel T (1995) Eur J Pharm Sci 3:215–230CrossRefGoogle Scholar

Copyright information

© SBIC 2007

Authors and Affiliations

  • Susana Beatriz Etcheverry
    • 1
    • 2
  • Evelina Gloria Ferrer
    • 1
  • Luciana Naso
    • 1
  • Josefina Rivadeneira
    • 1
    • 2
  • Victoria Salinas
    • 1
  • Patricia Ana María Williams
    • 1
  1. 1.Centro de Química Inorgánica (CEQUINOR/CONICET,UNLP), Facultad de Ciencias ExactasUniversidad Nacional de La PlataLa PlataArgentina
  2. 2.Cátedra de Bioquímica Patológica, Facultad de Ciencias ExactasUniversidad Nacional de La PlataLa PlataArgentina

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