Skip to main content

Advertisement

Log in

Boric Acid Reduces the Formation of DNA Double Strand Breaks and Accelerates Wound Healing Process

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Boron is absorbed by the digestive and respiratory system, and it was considered that it is converted to boric acid (BA), which was distributed to all tissues above 90 %. The biochemical essentiality of boron element is caused by boric acid because it affects the activity of several enzymes involved in the metabolism. DNA damage repair mechanisms and oxidative stress regulation is quite important in the transition stage from normal to cancerous cells; thus, this study was conducted to investigate the protective effect of boric acid on DNA damage and wound healing in human epithelial cell line. For this purpose, the amount of DNA damage occurred with irinotecan (CPT-11), etoposide (ETP), doxorubicin (Doxo), and H2O2 was determined by immunofluorescence through phosphorylation of H2AX(Ser139) and pATM(Ser1981) in the absence and presence of BA. Moreover, the effect of BA on wound healing has been investigated in epithelial cells treated with these agents. Our results demonstrated that H2AX(Ser139) foci numbers were significantly decreased in the presence of BA while wound healing was accelerated by BA compared to that in the control and only drug-treated cells. Eventually, the results indicate that BA reduced the formation of DNA double strand breaks caused by agents as well as improving the wound healing process. Therefore, we suggest that boric acid has important therapeutical effectiveness and may be used in the treatment of inflammatory diseases where oxidative stress and wound healing process plays an important role.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Henderson K, Stella S, Kobylewski S, Eckhert CD (2009) Receptor activated Ca2+ release is inhibited by boric acid in prostate cancer cells. PLoS One 4(6):1–10

    Article  Google Scholar 

  2. Nielsen FH, Meacham SL (2011) Growing evidence for human health benefits of boron. Journal of Evidence-Based Complementary & Alternative Medicine 16(3):169–180

    Article  CAS  Google Scholar 

  3. Nielsen FH (1996) Evidence for the nutritional essentiality of boron. J Trace Elem Exp Med 9:215–229

    Article  CAS  Google Scholar 

  4. Benderdour M, Bui-Van T, Dicko A, Belleville F (1998) In vivo and in vitro effects of boron and boronated compounds. J Trace Elem Med Biol 12(1):2–7

    Article  CAS  PubMed  Google Scholar 

  5. Korkmaz M, Avcı CB, Gunduz C, Aygunes D, Tepedelen BE (2014) Disodium pentaborate decahydrate (DPD) induced apoptosis by decreasing hTERT enzyme activity and disrupting F-actin organization of prostate cancer cells. Tumor Biol 35:1531–1538

    Article  CAS  Google Scholar 

  6. Gallardo-Williams MT, Maronpot RR, Wine RN, Brunssen SH, Chapin RE (2003) Inhibition of the enzymatic activity of prostate-specific antigen by boric acid and 3-nitrophenyl boronic acid. Prostate 54:44–49

    Article  PubMed  Google Scholar 

  7. Bradke TM, Hall C, Carper SW, Plopper GE (2008) Phenylboronic acid selectively inhibits human prostate and breast cancer cell migration and decreases viability. Cell Adhes Migr 2(3):153–160

    Article  Google Scholar 

  8. Mcauley EM, Bradke TA, Plopper GE (2011) Phenylboronic acid is a more potent inhibitor than boric acid of key signaling networks involved in cancer cell migration. Cell Adhes Migr 5(5):382–386

    Article  Google Scholar 

  9. Scorei RI, Popa R Jr (2010) Boron-containing compounds as preventive and chemotherapeutic agents for cancer. Anti Cancer Agents Med Chem 10(4):346–351

    Article  CAS  Google Scholar 

  10. Korkmaz M, Yenigün M, Bakırdere S, Ataman OY, Keskin S, Muezzinoglu T, Lekili M (2011) Effects of chronic boron exposure on semen profile. Biol Trace Elem Res 143(2):738–750

    Article  CAS  PubMed  Google Scholar 

  11. Duydu Y, Başaran N, Ustundag A, Aydın S, Undeger U, Ataman OY, Aydos K, Duker Y, Ickstadt K, Waltrup BS, Golka K, Bolt HM (2011) Reproductive toxicity parameters and biological monitoring in occupationally and environmentally boron-exposed persons in Bandırma, Turkey. Arch Toxicol 85:589–600

    Article  CAS  PubMed  Google Scholar 

  12. Dinant C, Houtsmuller AB, Vermeulen W (2008) Chromatin structure and DNA damage repair. Epigenetics Chromatin 1:9

    Article  PubMed  PubMed Central  Google Scholar 

  13. Huen MS, Chen JB (2008) The DNA damage response pathways: at the crossroad of protein modifications. Cell Res 18:8–16

    Article  CAS  PubMed  Google Scholar 

  14. Khanna KK, Jackson SP (2001) DNA double-strand breaks: signaling, repair and the cancer connection. Nat Genet 27:247–254

    Article  CAS  PubMed  Google Scholar 

  15. Shrivastav M, De Haro LP, Nickoloff JA (2008) Regulation of DNA double-strand break repair pathway choice. Cell Res 18:134–147

    Article  CAS  PubMed  Google Scholar 

  16. Jackson SP, Bartek J (2009) The DNA-damage response in human biology and disease. Nature 461:1071–1078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Lees-Miller SP, Meek K (2003) Repair of DNA double strand breaks by non- homologous end joining. Biochimie 85:1161–1173

    Article  CAS  PubMed  Google Scholar 

  18. Czornak K, Chughtai S, Chrzanowska KH (2008) Mystery of DNA repair: the role of the MRN complex and ATM kinase in DNA damage repair. J Appl Genet 49:383–396

    Article  PubMed  Google Scholar 

  19. O'Driscoll M, Jeggo PA (2006) The role of double-strand break repair—insights from human genetics. Nat Rev Genet 7:45–54

    Article  PubMed  Google Scholar 

  20. Lieber MR, Ma Y, Pannicke U, Schwarz K (2003) Mechanism and regulation of human non-homologous DNA end-joining. Nat Rev Mol Cell Biol 4:712–720

    Article  CAS  PubMed  Google Scholar 

  21. Ohnishi T, Mori E, Takahashi A (2009) DNA double-strand breaks: their production, recognition, and repair in eukaryotes. Mutat Res 669:8–12

    Article  CAS  PubMed  Google Scholar 

  22. Huang X, Halicka HD, Traganos F, Tanaka T, Kurose A, Darzynkiewicz Z (2005) Cytometric assessment of DNA damage in relation to cell cycle phase and apoptosis. Cell Prolif 38:223–243

    Article  PubMed  PubMed Central  Google Scholar 

  23. Chapin RE, Ku WW, Kenney MA, McCoy H (1998) The effects of dietary boric acid on bone strength in rats. Biol Tr Elem Res 66:395–399

    Article  CAS  Google Scholar 

  24. Barranco WT, Hudak PF, Eckhert, C.D (2007) Evaluation of ecological and in vitro effects of boron on prostate cancer risk (United States). Cancer Causes Control 18:71–77.

  25. Ince S, Kucukkurt I, Cigerci IH, Fidan AF, Eryavuz A (2010) The effects of dietary boric acid and borax supplementation on lipid peroxidation, antioxidant activity, and DNA damage in rats. J Trace Elem Med Biol 24:161–164

    Article  CAS  PubMed  Google Scholar 

  26. Scorei R, Mitrut P, Petrisor J, Scorei I (2011) A double-blind, placebo-controlled pilot study to evaluate the effect of calcium fructoborate on systemic inflammation and dyslipidemia markers for middle-aged people with primary osteoarthritis. Biol Trace Elem Res. doi:10.1007/s12011-011-9083-0

    PubMed Central  Google Scholar 

  27. Nzietchueng RM, Dousset B, Franck P, Benderdour M, Nabet P, Hess K (2002) Mechanisms implicated in the effects of boron on wound healing. J Trace Elem Med Biol 16(4):239–244

    Article  CAS  PubMed  Google Scholar 

  28. Durick KA, Tomita M, Hunt C, Bradley D (2005) Evidence that boron down-regulates inflammation through the NF-KB pathway [abstract]. The Federation of American Societies for Experimental Biology Journal 19(5):A1705

    Google Scholar 

  29. Benderdour M, Van Bui T, Hess K, Dicko A, Belleville F, Dousset BJ (2000) Effects of boron derivatives on extracellular matrix formation. J Trace Elem Med Biol 14(3):168–173

    Article  CAS  PubMed  Google Scholar 

  30. Benderdour M, Hess K, Dzondo-Gadet M, Dousset B, Nabet P, Belleville F (1997) Effect of boric acid solution on cartilage metabolism. Biochem Biophys Res Comm 234:263–268

    Article  CAS  PubMed  Google Scholar 

  31. Benderdour M, Van Bui T, Hess K, Dicko A, Belleville F, Dousset BJ (2000) Effects of boron derivatives on extracellular matrix formation. J Trace Elem Med Biol 14(3):168–173

    Article  CAS  PubMed  Google Scholar 

  32. Borrelly J, Blech MF, Grosdidier G, Martin-Thomas C, Hartemann P (1991) Contribution of a 3% solution of boric acid in the treatment of deep wounds with loss of substance. Ann Chir Plast Esthet 36(1):65–69

    CAS  PubMed  Google Scholar 

  33. Hunt CD, Idso JP (1999) Dietary boron as a physiological regulator of the normal inflammatory response: a review and current research progress. The Journal of Trace Elements in Experimental Medicine 12:221–233

    Article  CAS  Google Scholar 

  34. Yılmaz S, Ustundag A, Ulker OC, Duydu Y (2016) Protective effect of boric acid on oxidative DNA damage in Chinese hamster lung fibroblast V79 cell lines. CELL JOURNAL (Yakhteh) 17-4:748–754

    Google Scholar 

  35. Devirian TA, Volpe S (2003) The physiological effects of dietary boron. Crit Rev Food Sci Nutr 43:219–231

    Article  CAS  PubMed  Google Scholar 

  36. Turkez H, Geyikoglu F (2010) Boric acid: a potential chemoprotective agent against aflatoxin b1 toxicity in human blood. Cytotechnology 62:157–165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Türkez H, Geyikoğlu F, Tatar A, Keleş S, Ozkan A (2007) Effects of some boron compounds on peripheral human blood. Z Naturforsch C 62(11–12):889–896

    PubMed  Google Scholar 

  38. Dzondo-Gadet M, Mayap-Nzietchueng R, Hess K, Nabet P, Belleville F, Dousset B (2002) Action of boron at the molecular level: effects on transcription and translation in an acellular system. Biol Trace Elem Res 85(1):23–33

    Article  CAS  PubMed  Google Scholar 

  39. Turkez H (2008) Effects of boric acid and borax on titanium dioxide genotoxicity. J Appl Toxicol 28(5):658–664

    Article  CAS  PubMed  Google Scholar 

  40. Turkez H, Tatar A, Hacimuftuoglu A, Ozdemir E (2010) Boric acid as a protector against paclitaxel genotoxicity. Acta Biochim Pol 57(1):95–97

    CAS  PubMed  Google Scholar 

  41. Buldak RJ, Buldak L, Kukla M, Gabriel A, Żwirska-Korczala K (2014) Significance of selected antioxidant enzymes in cancer cell progression. Pol J Pathol 65(3):167–175

    Article  PubMed  Google Scholar 

  42. Pastar I, Stojadinovic O, Yin NC, Ramirez H, Nusbaum AG, Sawaya A, Patel SB, Khalid L, Isseroff RR, Tomic-Canic M (2014) Epithelialization in wound healing: a comprehensive review. Adv Wound Care (New Rochelle) 2014 1 3(7):445–464

    Google Scholar 

  43. Wong J, Tran LT, Magun EA, Magun BE, Wood L.J (2014) Production of IL-1β by bone marrow-derived macrophages in response to chemotherapeutic drugs: synergistic effects of doxorubicin and vincristine. Cancer Biology & Therapy, 15:10, 1395–1403.

Download references

Acknowledgments

We would like to thank the National Boron Research Institute, BOREN, for providing boric acid (BA). Also, we would like to thank Dr. Ismet Delıloglu Gurhan (Ege University, Izmır, Turkey) for providing HS-2 human normal epithelial cell line. This research was supported with grants (TUBITAK 113S700) from the Turkish Scientific and Technological Research Council.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Burcu Erbaykent Tepedelen.

Ethics declarations

Conflict of Interest

The authors declare that they have no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tepedelen, B.E., Soya, E. & Korkmaz, M. Boric Acid Reduces the Formation of DNA Double Strand Breaks and Accelerates Wound Healing Process. Biol Trace Elem Res 174, 309–318 (2016). https://doi.org/10.1007/s12011-016-0729-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-016-0729-9

Keywords

Navigation