Skip to main content
SpringerLink
Log in

High Concentrations of Boric Acid Trigger Concentration-Dependent Oxidative Stress, Apoptotic Pathways and Morphological Alterations in DU-145 Human Prostate Cancer Cell Line

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

Abstract

Boric acid is known to regulate the proliferation of cancer cells. Prostate cancer is among the types of cancer with high mortality in men. There are a few numbers of studies investigating the effects of boric acid on prostate cancer cells. The objective of the present study was to assess the effects of boric acid at concentrations higher than that can be achieved in blood by dietary intake on DU-145 human prostate cancer cells for 24 h. Firstly, we determined the cytotoxic activity of boric acid (0 to 12.5 mM) on DU-145 human prostate cancer cells by using 3-(4, 5-dimethylthiazol, 2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) and defined the IC50 concentration of boric acid. Then, by employing the doses found in MTT, the levels of antioxidant-oxidant molecules and apoptotic proteins were measured and morphological changes were evaluated. We have concluded that boric acid caused oxidative stress, inhibition of cell growth, apoptosis, and morphological alterations in a concentration-dependent manner in DU-145 cells. Furthermore, treatments with increasing boric acid concentrations decreased the antioxidant levels in cells. We actually revealed that boric acid, known as an antioxidant, may prevent cell proliferation by acting as an oxidant in certain doses. Although the high IC50 concentration of boric acid is perceived to be negative, we think it provides important background for subsequent studies.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

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

Similar content being viewed by others

References

  1. Devirian TA, Volpe SL (2003) The physiological effects of dietary boron. Crit Rev Food Sci Nutr 43:219–231. https://doi.org/10.1080/10408690390826491

    Article  CAS  PubMed  Google Scholar 

  2. Moore JA (1997) An assessment of boric acid and borax using the IEHR evaluative process for assessing human developmental and reproductive toxicity of agents. Expert Scientific Committee Reprod Toxicol 11:123–160. https://doi.org/10.1016/S0890-6238(96)00204-3

    Article  CAS  PubMed  Google Scholar 

  3. Nielsen FH (1994) Biochemical and physiologic consequences of boron deprivation in humans. Environ Health Perspect 102:59–63. https://doi.org/10.1289/ehp.94102s759

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Pawa S, Ali S (2006) Boron ameliorates fulminant hepatic failure by counteracting the changes associated with the oxidative stress. Chem Biol Interact 160:89–98. https://doi.org/10.1016/j.cbi.2005.12.002

    Article  CAS  PubMed  Google Scholar 

  5. Barranco WT, Kim DH, Stella SL Jr, Eckhert CD (2008) Boric acid inhibits stored Ca(2+) release in DU-145 prostate cancer cells. Cell Biol Toxicol 25:309–320. https://doi.org/10.1007/s10565-008-9085-7

    Article  CAS  PubMed  Google Scholar 

  6. Gallardo-Williams MT, Chapin RE, King PE, Moser GJ, Goldsworthy TL, Morrison JP, Maronpot RR (2004) Boron supplementation inhibits the growth and local expression of IGF-1 in human prostate adenocarcinoma (LNCaP) tumors in nude mice. Toxicol Pathol 32(1):73–78. https://doi.org/10.1080/01926230490260899

    Article  CAS  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 2:153–160. https://doi.org/10.4161/cam.2.3.6484

    Article  Google Scholar 

  8. Zafar H, Ali S (2013) Boron inhibits the proliferating cell nuclear antigen index, molybdenum containing proteins and ameliorates oxidative stress in hepatocellular carcinoma. Arch Biochem Biophys 529:66–74. https://doi.org/10.1016/j.abb.2012.11.008

    Article  CAS  PubMed  Google Scholar 

  9. Kreeger PK, Lauffenburger DA (2010) Cancer systems biology: a network modeling perspective. Carcinogenesis 31:2–8. https://doi.org/10.1093/carcin/bgp261

    Article  CAS  PubMed  Google Scholar 

  10. Karantanos T, Corn PG, Thompson TC (2013) Prostate cancer progression after androgen deprivation therapy: mechanisms of castrate resistance and novel therapeutic approaches. Oncogene 32:5501–5511. https://doi.org/10.1038/onc.2013.206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Algaba F, Montironi R (2010) Impact of prostate cancer multifocality on its biology and treatment. J Endourol 24:799–804. https://doi.org/10.1089/end.2009.0462

    Article  PubMed  Google Scholar 

  12. Cui Y, Winton MI, Zhang ZF, Rainey C, Marshall J, De Kernion JB, Eckhert CD (2004) Dietary boron intake and prostate cancer risk. Oncol Rep 11:887–892. https://doi.org/10.3892/or.11.4.887

    Article  CAS  PubMed  Google Scholar 

  13. Barranco WT, Hudak PF, Eckhert CD (2007) Evaluation of ecological and in vitro effects of boron on prostate cancer risk. Cancer Causes Control 18:71–77. https://doi.org/10.1007/s10552-006-0077-8

    Article  PubMed  Google Scholar 

  14. Barranco W, Eckhert C (2004) Boric acid inhibits prostate cancer cell proliferation. Cancer Lett 216:21–29. https://doi.org/10.1016/j.canlet.2004.06.001

    Article  CAS  PubMed  Google Scholar 

  15. Barranco W, Eckhert CD (2006) Cellular changes in boric acid treated DU145 prostate cancer cells. Br J Cancer 94:884–890. https://doi.org/10.1038/sj.bjc.6603009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kobylewski SE, Henderson KA, Yamada KE, Eckhert CD (2017) Activation of the EIF2α/ATF4 and ATF6 pathways in DU-145 cells by boric acid at the concentration reported in men at the US mean boron intake. Biol Trace Elem Res 176:278–293. https://doi.org/10.1007/s12011-016-0824-y

    Article  CAS  PubMed  Google Scholar 

  17. Gornall AG, Bardawill CJ, David MM (1949) Determination of serum proteins by means of the biuret reaction. J Biol Chem 177:751–766

    CAS  PubMed  Google Scholar 

  18. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358. https://doi.org/10.1016/0003-2697(79)90738-3

    Article  CAS  PubMed  Google Scholar 

  19. Srivastava SK, Beutler E (1968) Accurate measurement of oxidized glutathione content of human, rabbit, and rat red blood cells and tissues. Anal Biochem 25:70–76. https://doi.org/10.1016/0003-2697(68)90082-1

    Article  CAS  PubMed  Google Scholar 

  20. Aebi H (1984) [13] Catalase in vitro. Methods Enzymol 105:121–126. https://doi.org/10.1016/S0076-6879(84)05016-3

    Article  CAS  Google Scholar 

  21. Sun Y, Oberley LW, Li Y (1988) A simple method for clinical assay of superoxide dismutase. Clin Chem 34:497–500

    Article  CAS  Google Scholar 

  22. Fischer AH, Jacobson KA, Rose J, Zeller R (2008) Hematoxylin and eosin staining of tissue and cell sections. Cold Spring Harb Protoc 2008:pdb.prot4986. https://doi.org/10.1101/pdb.prot4986

  23. Yiu PH, See J, Rajan A, Bong CFJ (2008) Boric acid levels in fresh noodles and fish ball. Am J Agric Biol Sci 3:476–481. https://doi.org/10.3844/ajabssp.2008.476.481

    Article  Google Scholar 

  24. Yang W, Gao X, Wang B (2003) Boronic acid compounds as potential pharmaceutical agents. Med Res Rev 23:346–368. https://doi.org/10.1002/med.10043

    Article  CAS  PubMed  Google Scholar 

  25. 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. https://doi.org/10.4161/cam.5.5.18162

    Article  Google Scholar 

  26. Deshayes S, Cabral H, Ishii T, Miura Y, Kobayashi S, Yamashita T, Matsumoto A, Miyahara Y, Nishiyama N, Kataoka K (2013) Phenylboronic acid-installed polymeric micelles for targeting sialylated epitopes in solid tumors. J Am Chem Soc 135(41):15501–15507. https://doi.org/10.1021/ja406406h

    Article  CAS  PubMed  Google Scholar 

  27. Canturk Z, Tunali Y, Korkmaz S, Gulbas Z (2016) Cytotoxic and apoptotic effects of boron compounds on leukemia cell line. Cytotechnology 68(1):87–93. https://doi.org/10.1007/s10616-014-9755-7

    Article  CAS  PubMed  Google Scholar 

  28. Mahabir S, Spitz MR, Barrera SL, Dong YQ, Eastham C, Forman MR (2008) Dietary boron and hormone replacement therapy as risk factors for lung cancer in women. Am J Epidemiol 167(9):1070–1080. https://doi.org/10.1093/aje/kwn021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Al-Ali R, Gonzalez-Sarmiento R (2017) High concentrations of boric acid induce autophagy in cancer cell lines. bioRxiv 192441:1–9. https://doi.org/10.1101/193441

  30. Kamiguti AS, Serrander L, Lin K, Harris RJ, Cawley JC, Allsup DJ, Slupsky JR, Krause KH, Zuzel M (2005) Expression and activity of NOX5 in the circulating malignant B cells of hairy cell leukemia. J Immunol 175:8424–8430. https://doi.org/10.4049/jimmunol.175.12.8424

    Article  CAS  PubMed  Google Scholar 

  31. Bai X, Ma Y, Zhang G (2015) Butein suppresses cervical cancer growth through the PI3K/AKT/mTOR pathway. Oncol Rep 33:3085–3092. https://doi.org/10.3892/or.2015.3922

    Article  CAS  PubMed  Google Scholar 

  32. Kim DH, Park KW, Chae IG, Kundu J, Kim EH, Kundu JK, Chun KS (2016) Carnosic acid inhibits STAT3 signaling and induces apoptosis through generation of ROS in human colon cancer HCT116 cells. Mol Carcinog 55:1096–1110. https://doi.org/10.1002/mc.22353

    Article  CAS  PubMed  Google Scholar 

  33. You BR, Shin HR, Han BR, Kim SH, Park WH (2015) Auranofin induces apoptosis and necrosis in HeLa cells via oxidative stress and glutathione depletion. Mol Med Rep 11:1428–1434. https://doi.org/10.3892/mmr.2014.2830

    Article  CAS  PubMed  Google Scholar 

  34. Türkez H, Geyikoğlu F, Tatar A, Keleş S, Ozkan A (2007) Effects of some boron compounds on peripheral human blood. Z Naturforsch C 62:889–896. https://doi.org/10.1515/znc-2007-11-1218

    Article  PubMed  Google Scholar 

  35. Kim H, Oh E, Im H, Mun J, Yang M, Khim JY, Lee E, Lim SH, Kong MH, Lee M, Sul D (2006) Oxidative damages in the DNA, lipids, and proteins of rats exposed to isofluranes and alcohols. Toxicology 220:169–178. https://doi.org/10.1016/j.tox.2005.12.010

    Article  CAS  PubMed  Google Scholar 

  36. Meister A (1983) Selective modification of glutathione metabolism. Science 220:472–477. https://doi.org/10.1126/science.6836290

    Article  CAS  PubMed  Google Scholar 

  37. Ortega AL, Mena S, Estrela JM (2011) Glutathione in cancer cell death. Cancers (Basel) 3(1):1285–1310. https://doi.org/10.3390/cancers3011285

    Article  CAS  Google Scholar 

  38. He W, Liu R, Yang SH, Yuan F (2015) Chemotherapeutic effect of tamoxifen on temozolomide-resistant gliomas. Anti-Cancer Drugs 26:293–300. https://doi.org/10.1097/CAD.0000000000000197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Matsuura K, Canfield K, Feng W, Kurokawa M (2016) Metabolic regulation of apoptosis in cancer. Int Rev Cell Mol Biol 327:43–87. https://doi.org/10.1016/bs.ircmb.2016.06.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Gogvadze V, Orrenius S, Zhivotovsky B (2006) Multiple pathways of cytochrome c release from mitochondria in apoptosis. Biochim Biophys Acta 1757(5-6):639–647. https://doi.org/10.1016/j.bbabio.2006.03.016

    Article  CAS  PubMed  Google Scholar 

  41. Seervi M, Xue D (2015) Mitochondrial cell death pathways in Caenorhabiditis elegans. Curr Top Dev Biol 114:43–65. https://doi.org/10.1016/bs.ctdb.2015.07.019

    Article  CAS  PubMed  Google Scholar 

  42. Barranco WT, Eckhert CD (2004) Boric acid inhibits human prostate cancer cell proliferation. Cancer Lett 216:21–29. https://doi.org/10.1016/j.canlet.2004.06.001

    Article  CAS  PubMed  Google Scholar 

  43. Wu M, Zhang H, Hu J, Weng Z, Li C, Li H, Zhao Y, Mei X, Ren F, Li L (2013) Isoalantolactone inhibits UM-SCC-10A cell growth via cell cycle arrest and apoptosis induction. PLoS One 8:76000. https://doi.org/10.1371/journal.pone.0076000

    Article  CAS  Google Scholar 

  44. Honda T, Coppola S, Ghibelli L, Cho SH, Kagawa S, Spurgers KB, Brisbay SM, Roth JA, Meyn RE, Fang B, McDonnell TJ (2004) GSH depletion enhances adenoviral bax-induced apoptosis in lung cancer cells. Cancer Gene Ther 11(4):249–255. https://doi.org/10.1038/sj.cgt.7700684

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Biochemistry, Faculty of Medicine, Duzce University, Duzce, Turkey

    Ceyhan Hacioglu

  2. Department of Medical Biochemistry, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey

    Fatih Kar & Gungor Kanbak

  3. Department of Histology and Embryology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey

    Sedat Kacar & Varol Sahinturk

Authors
  1. Ceyhan Hacioglu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fatih Kar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sedat Kacar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Varol Sahinturk
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gungor Kanbak
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ceyhan Hacioglu.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hacioglu, C., Kar, F., Kacar, S. et al. High Concentrations of Boric Acid Trigger Concentration-Dependent Oxidative Stress, Apoptotic Pathways and Morphological Alterations in DU-145 Human Prostate Cancer Cell Line. Biol Trace Elem Res 193, 400–409 (2020). https://doi.org/10.1007/s12011-019-01739-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-019-01739-x

Keywords

Search

Navigation