Skip to main content
SpringerLink
Log in

Calcium Fructoborate Prevents Skin Cancer Development in Balb-c Mice: Next Part, Reverse Inflammation, and Metabolic Alteration

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

Abstract

Metabolic alterations and inflammation are regarded as hallmarks of cancer. Glycolytic flux and intermediate accumulation lead to the production of building blocks and NADPH which is important in protecting the cell from oxidative damage. Inflammation causes the release of mediators responsible for regulating molecular mechanism affecting metabolic pathways. CaFB due to its cis-diol-rich feature may have the potential to interact with molecules taking part in cancer development. This study was aimed to investigate the effects of CaFB on metabolic alterations and inflammation in 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin cancer. For this purpose, 92 Balb-c mice were distributed into 6 groups as control, CaFB, DMBA/TPA (D-T), treatment 1 (T1), 2 (T2), and 3(T3). Apart from control and CaFB in other groups, tumors initiated with 97.5-nmol DMBA and 6.5-nmol TPA. Treatment groups received 3 mg/kg/day CaFB with DMBA (T1), with TPA (T2), and after tumor formation (T3). In the D-T group, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity, 6-phosphogluconate dehydrogenase (PGD), glutathione (GSH), interleukin 6 (IL-6), (IL-1β), tumor necrosis factor-α (TNF-α) levels increased (p < 0.001) while malondialdehyde (MDA) levels decreased (p < 0.001) compared with that in control. CaFB application ameliorated DMBA-TPA effect according to the distribution time. It is noteworthy to consider CaFB as a potential preventive agent in skin cancer development.

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

Similar content being viewed by others

References

  1. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674

    CAS  PubMed  Google Scholar 

  2. Cairns RA, Harris IS, Mak TW (2011) Regulation of cancer cell metabolism. Nat Rev Cancer 11:85–95. https://doi.org/10.1038/nrc2981

    Article  CAS  PubMed  Google Scholar 

  3. Cantor JR, Sabatini DM (2012) Cancer cell metabolism: one hallmark, many faces. Cancer Discov 2:881–898. https://doi.org/10.1158/2159-8290.CD-12-0345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Vander Heiden MG (2011) Targeting cancer metabolism: a therapeutic window opens. Nat Rev Drug Discov 10:671–684. https://doi.org/10.1038/nrd3504

    Article  CAS  PubMed  Google Scholar 

  5. Gottfried E, Kreutz M, Mackensen A (2012) Tumor metabolism as modulator of immune response and tumor progression. Semin Cancer Biol 22:335–341. https://doi.org/10.1016/j.semcancer.2012.02.009

    Article  CAS  PubMed  Google Scholar 

  6. Patra KC, Hay N (2014) The pentose phosphate pathway and cancer. Trends Biochem Sci 39:347–354. https://doi.org/10.1016/j.tibs.2014.06.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Lund AW, Medler TR, Leachman SA, Coussens LM (2016) Lymphatic vessels, inflammation, and immunity in skin cancer. Cancer Discov 6:22–35. https://doi.org/10.1158/2159-8290.CD-15-0023

    Article  CAS  PubMed  Google Scholar 

  8. Yadav U, Anjaria KB, Nairy R, Shirsath KB, Desai UN, Chaurasia RK, Bhat NN, Sapra BK (2017) Differential killing and radio-modifying effects of iodoacetate in mammalian normal and cancer cells. Radiat Environ Biophys 56:227–239. https://doi.org/10.1007/s00411-017-0699-0

    Article  CAS  PubMed  Google Scholar 

  9. Shindo Y, Witt E, Han D, Epstein W, Packer L (1994) Enzymic and non-enzymic antioxidants in epidermis and dermis of human skin. J Invest Dermatol 102:122–124. https://doi.org/10.1111/1523-1747.ep12371744

    Article  CAS  PubMed  Google Scholar 

  10. Abel EL, Angel JM, Kiguchi K, DiGiovanni J (2009) Multi-stage chemical carcinogenesis in mouse skin: fundamentals and applications. Nat Protoc 4:1350–1362. https://doi.org/10.1038/nprot.2009.120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Sati J, Mohanty BP, Garg ML, Koul A (2016) Pro-oxidant role of silibinin in DMBA/TPA induced skin cancer: 1H NMR metabolomic and biochemical study. PLoS One 11:e0158955. https://doi.org/10.1371/journal.pone.0158955

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Scorei ID, Scorei RI (2013) Calcium fructoborate helps control inflammation associated with diminished bone health. Biol Trace Elem Res 155:315–321. https://doi.org/10.1007/s12011-013-9800-y

    Article  CAS  PubMed  Google Scholar 

  13. Kisacam MA, Kocamuftuoglu GO, Ozan IE, Yaman M, Ozan ST (2020) Calcium fructoborate prevents skin cancer development in balb-c mice. Biol Trace Elem Res 196:131–144. https://doi.org/10.1007/s12011-019-01897-y

    Article  CAS  PubMed  Google Scholar 

  14. Hunt CD, Idso JP (1999) Dietary boron as a physiological regulator of the normal inflammatory response: a review and current research progress. J Trace Elem Exp Med 12:221–233. https://doi.org/10.1002/(SICI)1520-670X(1999)12:3<221::AID-JTRA6>3.0.CO;2-X

    Article  CAS  Google Scholar 

  15. Donoiu I, Militaru C, Obleagă O, Hunter JM, Neamţu J, Biţă A, Scorei IR, Rogoveanu OC (2018) Effects of boron-containing compounds on cardiovascular disease risk factors – a review. J Trace Elem Med Biol 50:47–56. https://doi.org/10.1016/j.jtemb.2018.06.003

    Article  CAS  PubMed  Google Scholar 

  16. Hunter JM, Nemzer BV, Rangavajla N, Biţă A, Rogoveanu OC, Neamţu J, Scorei IR, Bejenaru LE, Rău G, Bejenaru C, Mogoşanu GD (2019) The fructoborates: part of a family of naturally occurring sugar–borate complexes—biochemistry, physiology, and impact on human health: a review. Biol Trace Elem Res 188:11–25. https://doi.org/10.1007/s12011-018-1550-4

    Article  CAS  PubMed  Google Scholar 

  17. Miljkovic D (1999) Boron carbohydrate complexes and uses thereof. US Pat. 5962049 A

  18. Placer ZA, Cushman LL, Johnson BC (1966) Estimation of product of lipid peroxidation (malonyl dialdehyde) in biochemical systems. Anal Biochem 16:359–364. https://doi.org/10.1016/0003-2697(66)90167-9

    Article  CAS  PubMed  Google Scholar 

  19. Chavan S, Sava L, Saxena V, Pillai S, Sontakke A, Ingole D (2005) Reduced glutathione: importance of specimen collection. Indian J Clin Biochem 20:150–152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Arora N, Bansal MP, Koul A (2013) Azadirachta indica acts as a pro-oxidant and modulates cell cycle associated proteins during DMBA/TPA induced skin carcinogenesis in mice. Cell Biochem Funct 31:385–394. https://doi.org/10.1002/cbf.2909

    Article  CAS  PubMed  Google Scholar 

  21. Surh Y-J, Kundu JK (2007) Cancer preventive phytochemicals as speed breakers in inflammatory signaling involved in aberrant COX-2 expression. Curr Cancer Drug Targets 7:447–458. https://doi.org/10.2174/156800907781386551

    Article  CAS  PubMed  Google Scholar 

  22. Altenberg B, Greulich KO (2004) Genes of glycolysis are ubiquitously overexpressed in 24 cancer classes. Genomics 84:1014–1020. https://doi.org/10.1016/j.ygeno.2004.08.010

    Article  CAS  PubMed  Google Scholar 

  23. Sirover MA (2005) New nuclear functions of the glycolytic protein, glyceraldehyde-3-phosphate dehydrogenase, in mammalian cells. J Cell Biochem 95:45–52. https://doi.org/10.1002/jcb.20399

    Article  CAS  PubMed  Google Scholar 

  24. Bonnet S, Archer SL, Allalunis-Turner J, Haromy A, Beaulieu C, Thompson R, Lee CT, Lopaschuk GD, Puttagunta L, Bonnet S, Harry G, Hashimoto K, Porter CJ, Andrade MA, Thebaud B, Michelakis ED (2007) A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth. Cancer Cell 11:37–51. https://doi.org/10.1016/j.ccr.2006.10.020

    Article  CAS  PubMed  Google Scholar 

  25. Kaneshima H, Kitsutaka T, Akagi M (1968) Studies on metabolic effects of borate (VII). Food Hyg Saf Sci (Shokuhin Eiseigaku Zasshi) 9:303–308. https://doi.org/10.3358/shokueishi.9.303

    Article  CAS  Google Scholar 

  26. Chang C-H, Curtis JD, Maggi LB, Faubert B, Villarino AV, O’Sullivan D, Huang SC-C, van der Windt GJW, Blagih J, Qiu J, Weber JD, Pearce EJ, Jones RG, Pearce EL (2013) Posttranscriptional control of T cell effector function by aerobic glycolysis. Cell 153:1239–1251. https://doi.org/10.1016/j.cell.2013.05.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Krasnov GS, Dmitriev AA, Snezhkina AV, Kudryavtseva AV (2013) Deregulation of glycolysis in cancer: glyceraldehyde-3-phosphate dehydrogenase as a therapeutic target. Expert Opin Ther Targets 17:681–693. https://doi.org/10.1517/14728222.2013.775253

    Article  CAS  PubMed  Google Scholar 

  28. Kuehne A, Emmert H, Soehle J, Winnefeld M, Fischer F, Wenck H, Gallinat S, Terstegen L, Lucius R, Hildebrand J, Zamboni N (2015) Acute activation of oxidative pentose phosphate pathway as first-line response to oxidative stress in human skin cells. Mol Cell 59:359–371. https://doi.org/10.1016/j.molcel.2015.06.017

    Article  CAS  PubMed  Google Scholar 

  29. Lin R, Elf S, Shan C, Kang H-B, Ji Q, Zhou L, Hitosugi T, Zhang L, Zhang S, Seo JH, Xie J, Tucker M, Gu T-L, Sudderth J, Jiang L, Mitsche M, DeBerardinis RJ, Wu S, Li Y, Mao H, Chen PR, Wang D, Chen GZ, Hurwitz SJ, Lonial S, Arellano ML, Khoury HJ, Khuri FR, Lee BH, Lei Q, Brat DJ, Ye K, Boggon TJ, He C, Kang S, Fan J, Chen J (2015) 6-Phosphogluconate dehydrogenase links oxidative PPP, lipogenesis and tumour growth by inhibiting LKB1–AMPK signalling. Nat Cell Biol 17:1484–1496. https://doi.org/10.1038/ncb3255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Rolfs F, Huber M, Kuehne A, Kramer S, Haertel E, Muzumdar S, Wagner J, Tanner Y, Böhm F, Smola S, Zamboni N, Levesque MP, Dummer R, Beer HD, Hohl D, Werner S, Schäfer M (2015) Nrf2 activation promotes keratinocyte survival during early skin carcinogenesis via metabolic alterations. Cancer Res 75:4817–4829. https://doi.org/10.1158/0008-5472.CAN-15-0614

    Article  CAS  PubMed  Google Scholar 

  31. Kurtoglu V, Kurtoglu F, Akalin PP (2018) The effects of various levels of boron supplementation on live weight, plasma lipid peroxidation, several biochemical and tissue antioxidant parameters of male mice. J Trace Elem Med Biol 49:146–150. https://doi.org/10.1016/j.jtemb.2018.05.013

    Article  CAS  PubMed  Google Scholar 

  32. Monga J, Chauhan CS, Sharma M (2011) Human epithelial carcinoma cytotoxicity and inhibition of DMBA/TPA induced squamous cell carcinoma in Balb/c mice by Acacia catechu heartwood. J Pharm Pharmacol 63:1470–1482. https://doi.org/10.1111/j.2042-7158.2011.01354.x

    Article  CAS  PubMed  Google Scholar 

  33. Sharma S, Khan N, Sultana S (2004) Study on prevention of two-stage skin carcinogenesis by Hibiscus rosa sinensis extract and the role of its chemical constituent, gentisic acid, in the inhibition of tumour promotion response and oxidative stress in mice. Eur J Cancer Prev 13:53–63. https://doi.org/10.1097/00008469-200402000-00009

    Article  CAS  PubMed  Google Scholar 

  34. Koul A, Mukherjee N, Gangar SC (2006) Inhibitory effects of Azadirachta indica on DMBA-induced skin carcinogenesis in balb/c mice. Mol Cell Biochem 283:47–55. https://doi.org/10.1007/s11010-006-2269-7

    Article  CAS  PubMed  Google Scholar 

  35. Md Roduan MR, Hamid RA, Sulaiman H, Mohtarrudin N (2017) Annona muricata leaves extracts prevent DMBA/TPA-induced skin tumorigenesis via modulating antioxidants enzymes system in ICR mice. Biomed Pharmacother 94:481–488. https://doi.org/10.1016/j.biopha.2017.07.133

    Article  CAS  PubMed  Google Scholar 

  36. Masre SF, Izzuddeen A, John DNS, Hamid ZA (2019) The effects of oleuropein on apoptotic rate and oxidative stress profiles during tumour promotion stage in the mouse skin carcinogenesis model. Sains Malaysiana 48:347–352. https://doi.org/10.17576/jsm-2019-4802-11

    Article  CAS  Google Scholar 

  37. Scorei RI, Rotaru P (2011) Calcium fructoborate — potential anti-inflammatory agent. Biol Trace Elem Res 143:1223–1238. https://doi.org/10.1007/s12011-011-8972-6

    Article  CAS  PubMed  Google Scholar 

  38. Scorei R, Cimpoiasu V, Iordachescu D (2005) In vitro evaluation of the antioxidant activity of calcium fructoborate. Biol Trace Elem Res 107:127–134. https://doi.org/10.1385/BTER:107:2:127

    Article  CAS  PubMed  Google Scholar 

  39. Scorei R, Ciubar R, Iancu C, Mitran V, Cimpean A, Iordachescu D (2007) In vitro effects of calcium fructoborate on fMLP-stimulated human neutrophil granulocytes. Biol Trace Elem Res 118:27–37. https://doi.org/10.1007/s12011-007-0019-7

    Article  CAS  PubMed  Google Scholar 

  40. Kong YH, Xu SP (2018) Salidroside prevents skin carcinogenesis induced by DMBA/TPA in a mouse model through suppression of inflammation and promotion of apoptosis. Oncol Rep 39:2513–2526. https://doi.org/10.3892/or.2018.6381

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Hall IH, Das MK, Harchelroad F, Wisian-Neilson P, McPhail AT, Spielvogel BF (1981) Antihyperlipidemic activity of amine cyanoboranes, amine carboxyboranes, and related compounds. J Pharm Sci 70:339–341. https://doi.org/10.1002/jps.2600700333

    Article  CAS  PubMed  Google Scholar 

  42. Romero-Aguilar KS, Arciniega-Martínez IM, Farfán-García ED, Campos-Rodríguez R, Reséndiz-Albor AA, Soriano-Ursúa MA (2019) Effects of boron-containing compounds on immune responses: review and patenting trends. Expert Opin Ther Pat 29:339–351. https://doi.org/10.1080/13543776.2019.1612368

    Article  CAS  PubMed  Google Scholar 

  43. Scorei RI, Ciofrangeanu C, Ion R, Cimpean A, Galateanu B, Mitran V, Iordachescu D (2010) In vitro effects of calcium fructoborate upon production of inflammatory mediators by LPS-stimulated RAW 264.7 macrophages. Biol Trace Elem Res 135:334–344. https://doi.org/10.1007/s12011-009-8488-5

    Article  CAS  PubMed  Google Scholar 

  44. Hussain SA, Abood SJ, Gorial FI (2017) The adjuvant use of calcium fructoborate and borax with etanercept in patients with rheumatoid arthritis: pilot study. J Intercult Ethnopharmacol 6:58–64. https://doi.org/10.5455/jice.20161204021549

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This project was funded by the National Boron Institution of Turkey grant number: 2016-31-07-15-003.

Author information

Authors and Affiliations

  1. Department of Biochemistry, Faculty of Veterinary Medicine, Mustafa Kemal University, 31060, Hatay, Turkey

    Mehmet Ali Kisacam

  2. Department of Biochemistry, Faculty of Veterinary Medicine, Mehmet AkifErsoy University, 15030, Burdur, Turkey

    Gonca Ozan Kocamuftuoglu

  3. Department of Histology and Embryology, Faculty of Medicine, Firat University, 23200, Elazig, Turkey

    Ibrahim Enver Ozan

  4. Department of Chemistry, Faculty of Science, Firat University, 23200, Elazig, Turkey

    Mehmet Yaman

  5. Department of Biochemistry, Faculty of Veterinary Medicine, Firat University, 23200, Elazig, Turkey

    SemaTemizer Ozan

Authors
  1. Mehmet Ali Kisacam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gonca Ozan Kocamuftuoglu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ibrahim Enver Ozan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mehmet Yaman
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. SemaTemizer Ozan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mehmet Ali Kisacam.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All animal experiments were done according to the approval of the Animal Experimentation Ethics Committee of Firat University (Elazig, Turkey) (approval number 2016/27-78).

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

Kisacam, M.A., Kocamuftuoglu, G., Ozan, I.E. et al. Calcium Fructoborate Prevents Skin Cancer Development in Balb-c Mice: Next Part, Reverse Inflammation, and Metabolic Alteration. Biol Trace Elem Res 199, 2627–2634 (2021). https://doi.org/10.1007/s12011-020-02363-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-020-02363-w

Keywords

Search

Navigation