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Inhibitory effects of delphinidin and luteolin on genotoxicity induced by K2B3O3F4OH) in human lymphocytes in vitro

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Abstract

The genotoxicity of halogenated boroxine [K2(B3O3F4OH)], a novel compound with the potential for prevention and/or treatment of various skin changes, has been confirmed in human lymphocytes. The potential of luteolin and delphinidin in inhibition of the genotoxic and cytotoxic effects of halogenated boroxine in vitro was analyzed applying the chromosome aberration analysis and the cytokinesis-block micronucleus cytome assay in human lymphocyte cultures. The in vitro treatments included addition of boroxine and flavonoids independently, and combined treatments of boroxine with luteolin or delphinidin. In the concentration of 50 μ.M, luteolin significantly decreased the frequency of micronuclei and nuclear buds. Delphinidin suppressed the occurrence of aberrant cells in the presence of the halogenated boroxine, but also affected their induction in respective delphinidin treatment. Detection of endoreduplications in combined treatments indicated that these flavonoids are potential inhibitors of cell cycle or topoisomerase II activity. The obtained results have confirmed antigenotoxic activity of selected bioflavonoids in vitro. The side effects of potential therapeutic applications of halogenated boroxine may be inhibited in the presence of bioflavonoids in appropriate dosage.

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Abbreviations

ANOVA:

analysis of variance

DMSO:

dimethylsulfoxide

HB:

halogenated boroxine

NBs:

nuclear buds

NDCI:

nuclear division cytotoxicity index

NDI:

nuclear division index

NPBs:

nucleoplasmic bridges

References

  • Adams J.A., Behnke M., Chen S. Cruickshank A.A., Dick L.R., Grenier L., Klunder J.M., Ma Y.T., Plamondon L. & Stein R.L. 1998. Potent and selective inhibitors of the proteasome: dipeptidyl boronic acid. Bioorg. Med. Chem. Lett. 8: 333–338.

    Article  CAS  Google Scholar 

  • Azevedo L., Alves de Lima P.L., Gomes J.C., Stringheta P.C., Ribeiro D.A. & Salvadori D.M. 2007. Differential response related to genotoxicity between eggplant (Solarium melanogena) skin aqueous extract and its main purified anthocyanin (delphinidin) in vivo. Food. Chem. Toxicol. 45: 852–858.

    Article  CAS  Google Scholar 

  • Cantero G., Campanella C., Mateos S. & Cortés F. 2006. Topoisomerase II inhibition and high yield of endoreduplication induced by the flavonoids luteolin and quercetin. Mutagenesis 21: 321–325.

    Article  CAS  Google Scholar 

  • Cortes F., Pastor N., Mateos S. & Dominguez I. 2003. Roles of DNA topoisomerases in chromosome segregation and mitosis. Mutat. Res. 543: 59–66.

    Article  CAS  Google Scholar 

  • Eastmond D.A. & Tucker J.D. 1989. Identification of aneuplody-inducing agents using cytokinesis-blocked human lymphocytes and an antikinetochore antibody. Environ. Mol. Mutagen. 13: 34–43.

    Article  CAS  Google Scholar 

  • Esselen M., Fritz J., Hutter M. & Marko D. 2009. Delphinidin modulates the DNA-damaging properties of topoisomerase II poisons. Chem. Res. Toxicol. 22: 554–564.

    Article  CAS  Google Scholar 

  • Fenech M. 1998. Important variables that influence base-line micronucleus frequency in cytokinesis-blocked lymphocytes — a biomarker for DNA damage in human populations. Mutat. Res. 404: 155–165.

    Article  CAS  Google Scholar 

  • Fenech M. 2000. The in vitro micronucleus technique. Mutat. Res. 455: 81–95.

    Article  CAS  Google Scholar 

  • Fenech M., Chang W.P., Kirsch-Volders M., Holland N., Bonassi S. & Zeiger E. 2003. HUMN project: detailed description of the scoring criteria for the cytokinesis-block micronucleus assay using isolated human lymphocyte cultures. Mutat. Res. 534: 65–75.

    Article  CAS  Google Scholar 

  • Fenech M., Kirsch-Volders M., Natarajan A.T., Surralles J., Crott J.W., Parry J., Norppa H., Eastmond D.A., Tucker J.D. & Thomas P. 2011. Molecular mechanisms of micronucleus, nucleoplasmic bridge and nuclear bud formation in mammalian and human cells. Mutagenesis 26: 125–132.

    Article  CAS  Google Scholar 

  • Feng R., Wang S.Y., Shi Y.H., Fan J. & Yin X.M. 2010. Delphinidin induces necrosis in hepatocellular carcinoma cells in the presence of 3-methyladenine, an autophagy inhibitor. J. Agric. Food Chem. 58: 3957–3964.

    Article  CAS  Google Scholar 

  • Galic B. 2012. Boroxine composition for removal of skin changes. Inventor: Galic B. Int. CI. A61K3169, USA patent US8278289.

    Google Scholar 

  • Gasiorowski K., Szyba K., Brokos B., Kolaczynska B., Jankowiak-Wlodarczyk M. & Oszmianski J. 1997. Antimutagenic activity of anthocyanins isolated from Aronio, melanocarpa fruits. Cancer Lett. 119: 37–46.

    Article  CAS  Google Scholar 

  • Habermeyer M., Fritz J., Barthelmes H.U., Christensen M.O., Larsen M.K., Boege F. & Marko D. 2005. Anthocyanidins modulate the activity of human DNA topoisomerases I and II and affect cellular DNA integrity. Chem. Res. Toxicol. 18: 1395–1404.

    Article  CAS  Google Scholar 

  • Hafeez B.B., Siddiqui I.A., Asim M., Malik A., Afaq F., Adhami V.M., Saleem M., Din M. & Mukhtar H. 2008. A dietary an-thocyanidin delphinidin induces apoptosis of human prostate cancer PC3 cells in vitro and in vivo: involvement of nuclear factor-κB signaling. Cancer Res. 68: 8564–8572.

    Article  Google Scholar 

  • Hall D.G. 2006. Boronic Acids. John Wiley and Sons, New York.

    Google Scholar 

  • Hall L.L., Th’ng J.P., Guo X.W., Teplitz R.L. & Bradbury E.M. 1996. A brief staurosporine treatment of mitotic cells triggers premature exit from mitosis and polyploid cell formation. Cancer Res. 56: 3551–3559.

    CAS  PubMed  Google Scholar 

  • Haveric S., Haveric A., Bajrovic K., Galic B. & Maksimovic M. 2011. Effects of dipotassium trioxohydroxytetrafluorotribo-rate (K2[B3O3F4OH]) on genetic material and inhibition of cell division in human cell cultures. Drug Chem. Toxicol. 34: 250–254.

    Article  CAS  Google Scholar 

  • Heim K.E., Tagliaferro A.R. & Bobilya D.J. 2002. Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships. J. Nutr. Biochem. 13: 572–584.

    Article  CAS  Google Scholar 

  • Islamovic S., Galic B. & Milos M. 2014. A study of the inhibition of catalase by dipotassium-trioxohydroxytetrafluorotriborat K2[B3O3F4OH]. J. Enzyme Inhib. Med. Chem. 29: 744–748.

    Article  CAS  Google Scholar 

  • Ivanov A., Cragg M.S., Erenpreisa J., Emzinsh D., Lukman H. & Midge T.M. 2003. Endopolyploid cells produced after severe genotoxic damage have the potential to repair DNA double strand breaks. J. Cell Sci. 116: 4095–4106.

    Article  CAS  Google Scholar 

  • Lamy S., Blanchette M., Michaud-Levesque J., Lafleur R., Durocher Y., Moghrabi A., Barrette S., Gingras D., Beliveau R. 2006. Delphinidin, a dietary anthocyanidin, inhibits vascular endothelial growth factor receptor-2 phosphorylation. Carcinogenesis 27: 989–996.

    Article  CAS  Google Scholar 

  • Lin Y., Shi R., Wang X. & Shen H.M. 2008. Luteolin, a flavonoid with potentials for cancer prevention and therapy. Curr. Cancer Drug Targets 8: 634–646.

    Article  CAS  Google Scholar 

  • Liu L.F. 1989. DNA topoisomerase poisons as antitumor drugs. Annu. Rev. Biochem. 58: 351–375.

    Article  CAS  Google Scholar 

  • López-Lázaro M. 2009. Distribution and biological activities of the flavonoid luteolin. Mini Rev. Med. Chem. 9: 31–59.

    Article  Google Scholar 

  • López-Lázaro M., Willmore E. & Austin C.A. 2010. The dietary flavonoids myricetin and fisetin act as dual inhibitors of DNA topoisomerases I and II in cells. Mutat. Res. 696: 41–47.

    Article  Google Scholar 

  • Mitelman F., Mertens F. & Johansson B. 1997. A breakpoint map of recurrent chromosomal rearrangements in human neoplasia. Nat. Genet. 15: 417–474.

    Article  CAS  Google Scholar 

  • Paramore A. & Frantz S. 2003. Bortezomib. Nat. Rev. Drug Disc. 2: 611–612.

    Article  CAS  Google Scholar 

  • Ren W., Qiao Z., Wang H., Zhu L. & Zhang L. 2003. Flavonoids: promising anticancer agents. Med. Res. Rev. 23: 519–534.

    Article  CAS  Google Scholar 

  • Rusak G., Piantanida I., Masic L., Kapuralin K., Durgo K. & Kopjar N. 2010. Spectrophotometric analysis of flavonoid DNA interactions and DNA damaging/protecting and cytotoxic potential of flavonoids in human peripheral blood lymphocytes. Chem. Biol. Interact. 188: 181–189.

    Article  CAS  Google Scholar 

  • Ryss I.G. & Slutskaya M.M. 1951. Report on the platinum sector. Dokl. Akad. Nauk SSSR 26: 216.

    Google Scholar 

  • Sugihara N., Arakawa T., Ohnishi M. & Furuno K. 1999. Anti-and pro-oxidative effects of flavonoids on metal induced lipid hydroperoxide-dependent lipid peroxidation in cultured hep-atocytes loaded with α-linolenic acid. Free Radic. Biol. Med. 27: 1313–1323.

    Article  CAS  Google Scholar 

  • Sumner A.T. 1998. Induction of diplochromosomes in mammalian cells by inhibitors of topoisomerase II. Chromosoma 107: 486–490.

    Article  CAS  Google Scholar 

  • Thomas P., Umegaki K. & Fenech M. 2003. Nucleoplasms bridges are a sensitive measure of chromosome rearrangement in the cytokinesis-block micronucleus assay. Mutagenesis 18: 187–194.

    Article  CAS  Google Scholar 

  • Vullo D., Milos M., Galic B., Scozzafava A. & Supuran C.T. 2015. Dipotassium-trioxohydroxytetrafluorotriborate, K2(B303F40H), is a potent inhibitor of human carbonic an-hydrases. J. Enzyme Inhib. Med. Chem. 30: 341–344.

    Article  CAS  Google Scholar 

  • Wu X., Beecher G.R., Holden J.M., Haytowizt D.B., Gerbhardt S.E. & Prior R.L. 2006. Concentrations of anthocyanins in common foods in the United States and estimation of normal consumption. J. Agric. Food. Chem. 54: 4069–4075.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This research was supported by the Ministry of Education and Science of the Federation of Bosnia and Herzegovina [grant number 05-39-5613-1-2/11].

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Authors and Affiliations

  1. Laboratory for Cytogenetics and Genotoxicology, Institute for Genetic Engineering and Biotechnology, University of Sarajevo, Zmaja od Bosne 8 (Kampus), 71000, Sarajevo, Bosnia and Herzegovina

    Maida Hadžić, Sanin Haverić & Anja Haverić

  2. Department of Chemistry, Faculty of Natural Sciences and Mathematics, University of Sarajevo, Zmaja od Bosne 35, 71000, Sarajevo, Bosnia and Herzegovina

    Borivoj Galić

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  1. Maida Hadžić
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  2. Sanin Haverić
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  3. Anja Haverić
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  4. Borivoj Galić
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Correspondence to Maida Hadžić.

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Hadžić, M., Haverić, S., Haverić, A. et al. Inhibitory effects of delphinidin and luteolin on genotoxicity induced by K2B3O3F4OH) in human lymphocytes in vitro. Biologia 70, 553–558 (2015). https://doi.org/10.1515/biolog-2015-0066

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  • DOI: https://doi.org/10.1515/biolog-2015-0066

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