The antiproliferative and antimigrative effects of disodium octaborate tetrahydrate on A549 lung and DU 145 prostate cancer cells

Abstract

Disodium octaborate tetrahydrate (DOT) (Na2O.4B2O3.4H2O) is an inorganic salt form of boron, used in agriculture, insecticides, and antifungal in wood protection. As an important fine boride, DOT is non-toxic for humans. The antimicrobial and wound-healing properties, as well as the cytotoxicity of DOT against glioblastoma cells, were investigated in other studies. Although there are no studies about the cytotoxic potential of other cancer types of this compound. This is the first study to investigate the cytotoxic and wound closure inhibition effects of DOT on A549 lung and DU145 prostate cancer cell lines. Cytotoxicity was assessed using the MTT assay, and the IC₅₀ values for A549 and DU145 cells were calculated as 58.78 mM and 109.33 mM, respectively, indicating a dose-dependent reduction in cell viability. The effect on wound closure was evaluated using an in vitro scratch assay. At IC₅₀ concentrations, DOT significantly inhibited wound closure in both cell lines after 24 hours compared to controls. Although the relatively high IC₅₀ values limit direct therapeutic applicability, these preliminary findings demonstrate, for the first time, that DOT possesses biological activity against lung and prostate cancer cells. Further studies are warranted to explore its potential applications.

Keywords

• Boron
• A549
• DU 145
• Cyotoxicity
• Wound closure inhibition

Supporting Institution

A part of this publication is a part of a project supported by the Muğla Sıtkı Koçman University Scientific Research Projects Coordination Unit under project number 21/123/02/1/4.

Ethical Statement

Ethics committee certification is not required.

Thanks

We thank to Muğla Sıtkı Koçman University Scientific Research Projects Coordination Unit for their support.

Disodyum oktaborat tetrahidratın A549 akciğer ve DU 145 prostat kanseri hücreleri üzerindeki antiproliferatif ve antimigratif etkileri

Abstract

Disodyum oktaborat tetrahidrat (DOT) (Na2O.4B2O3.4H2O), tarımda, böcek ilaçlarında ve ahşap korumasında antifungal olarak kullanılan, borun inorganik bir tuz formudur. Önemli bir ince borür olan DOT, insanlar için toksik değildir. DOT'un antimikrobiyal ve yara iyileştirici özellikleri ile glioblastoma hücrelerine karşı sitotoksik etkisi diğer çalışmalarda araştırılmıştır. Bununla birlikte, bu bileşiğin diğer kanser türleri üzerindeki sitotoksik potansiyeli hakkında herhangi bir çalışma bulunmamaktadır. Bu çalışma, DOT'un A549 akciğer ve DU145 prostat kanseri hücre hatları üzerindeki antiproliferatif ve antimigratif etkilerini belirleyen ilk çalışmadır. DOT'un hücre göçü üzerindeki etkisi, in vitro çizik testi kullanılarak belirlenmiştir. A549 ve DU145 hücreleri için IC50 değerleri sırasıyla 59,55 mM ve 109,33 mM olarak tahmin edilmiştir. DOT'un A549 ve DU 145 hücreleri üzerindeki antiproliferatif etkisi doza bağlı olarak artmaktadır. İn vitro çizik testinde, DOT, kontrol grubuna kıyasla her iki hücre hattında da IC50 değerlerinde hücre göçünü inhibe etmiştir. Çalışma, DOT'un antiproliferatif ve antimigratuar etkileriyle kanser tedavisi için uygun bir aday olduğunu ortaya koymuştur. Bununla birlikte, klinik uygulamalarını desteklemek için daha in vivo çalışmaya ihtiyaç vardır.

Keywords

• Bor
• A549
• DU 145
• Sitotoksisite
• Yara kapanması inhibisyonu

Supporting Institution

Bu yayının bir kısmı, Muğla Sıtkı Koçman Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi tarafından 21/123/02/1/4 proje numarası kapsamında desteklenen projenin bir parçasıdır.

Ethical Statement

Etik kurul belgesi gerekmemektedir.

Thanks

Muğla Sıtkı Koçman Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi'ne katkılarından dolayı teşekkür ederim.

References

1. Khaliq, H., Juming, Z., & Ke-Mei, P. (2018). The physiological role of boron on health. Biological Trace Element Research, 186(1), 31–51. https://doi.org/10.1007/s12011-018-1284-3
2. Uluisik, I., Karakaya, H. C., & Koc, A. (2018). The importance of boron in biological systems. Journal of Trace Elements in Medicine and Biology, 45, 156-162. https://doi.org/10.1016/j.jtemb.2017.10.008
3. Scorei, I. R., & Popa, R. (2010). Boron-containing compounds as preventive and chemotherapeutic agents for cancer. Anti-Cancer Agents in Medicinal Chemistry, 10(4), 346-351. https://doi.org/10.2174/187152010791162289
4. Romero-Aguilar, K. S., Arciniega-Martínez, I. M., Farfán-García, E. D., Campos-Rodríguez, R., Reséndiz-Albor, A. A., & Soriano-Ursúa, M. A. (2019). Effects of boron-containing compounds on immune responses: Review and patenting trends. Expert Opinion on Therapeutic Patents, 29(5), 339-351. https://doi.org/10.1080/13543776.2019.1612368
5. Turkez, H. (2008). Effects of boric acid and borax on titanium dioxide genotoxicity. Journal of Applied Toxicology, 28(5), 658-664. https://doi.org/10.1002/jat.1318
6. Hosmane, N. S., Maguire, J. A., Zhu, Y., & Takagaki, M. (2011). Future perspectives for boron and gadolinium neutron capture therapies in cancer treatment. Boron and gadolinium neutron capture therapy for cancer treatment. World Scientific, 165-170. https://doi.org/10.1142/9789814338684_0009
7. Hosmane, N. S., & Eagling, R. D. (Eds.). (2018). Handbook of boron science: With applications in organometallics, catalysis, materials and medicine (Vols. 1-4). World Scientific. https://doi.org/10.1142/q0130
8. Turkez, H., & Geyikoglu, F. (2010). Boric acid: A potential chemoprotective agent against aflatoxin b1 toxicity in human blood. Cytotechnology, 62(2), 157-165. https://doi.org/10.1007/s10616-010-9272-2

9. Alak, G., Parlak, V., Yeltekin, A. Ç., Ucar, A., Çomaklı, S., Topal, A., … & Türkez, H. (2019). The protective effect exerted by dietary borax on toxicity metabolism in rainbow trout (Oncorhynchus mykiss) tissues. Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology, 216, 82-92. https://doi.org/10.1016/j.cbpc.2018.10.005
10. Lawler A. (1995). Cancer therapy: Brookhaven prepares for boron trials. Science, 267, 956. https://doi.org/10.1126/science.7695774
11. Cui, Y., Winton, M. I., Zhang, Z. F., Rainey, C., Marshall, J., De Kernion, J. B., & Eckhert, C. D. (2004). Dietary boron intake and prostate cancer risk. Oncology Reports, 11(4), 887-892.
12. Yinghuai, Z., & Hosmane, N. S. (2013). Applications and perspectives of boron-enriched nanocomposites in cancer therapy. Future Medicinal Chemistry, 5(6), 705-714. https://doi.org/10.4155/fmc.13.47
13. Ferreira, T. H., Marino, A., Rocca, A., Liakos, I., Nitti, S., Athanassiou, A., …& Ciofani, G. (2015). Folate-grafted boron nitride nanotubes: Possible exploitation in cancer therapy. International Journal of Pharmaceutics, 481(1-2), 56-63. https://doi.org/10.1016/j.ijpharm.2015.01.048
14. Schabath, M. B., Wu, X., Vassilopoulou-Sellin, R., Vaporciyan, A. A., & Spitz, M. R. (2004). Hormone replacement therapy and lung cancer risk: A case-control analysis. Clinical Cancer Research, 10(1), 113-123. https://doi.org/10.1158/1078-0432.ccr-0911-3
15. Wang, Y., Zhao, Y., & Chen, X. (2008). Experimental study on the estrogen-like effect of boric acid. Biological Trace Element Research, 121(2), 160-170. https://doi.org/10.1007/s12011-007-8041-3
16. Cebeci, E., Yüksel, B., & Şahin, F. (2022). Anti-cancer effect of boron derivatives on small-cell lung cancer. Journal of Trace Elements in Medicine and Biology: Organ of the Society for Minerals and Trace Elements, 70, 126923. https://doi.org/10.1016/j.jtemb.2022.126923
17. Korkmaz, M., Uzgören, E., Bakırdere, S., Aydın, F., & Ataman, O. Y. (2007). Effects of dietary boron on cervical cytopathology and on micronucleus frequency in exfoliated buccal cells. Environmental Toxicology: An International Journal, 22(1), 17-25. https://doi.org/10.1002/tox.20229
18. Gonzalez, A., Peters, U., Lampe, J. W., & White, E. (2007). Boron intake and prostate cancer risk. Cancer Causes & Control, 18(10), 1131-1140. https://doi.org/10.1007/s10552-007-9052-2
19. Scorei, R., Ciubar, R., Ciofrangeanu, C. M., Mitran, V., Cimpean, A., & Iordachescu, D. (2008). Comparative effects of boric acid and calcium fructoborate on breast cancer cells. Biological Trace Element Research, 122(3), 197-205. https://doi.org/10.1007/s12011-007-8081-8
20. Portu, A., Molinari, A. J., Thorp, S. I., Pozzi, E. C. C., Curotto, P., Schwint, A. E., & Saint Martin, G. (2015). Neutron autoradiography to study boron compound microdistribution in an oral cancer model. International Journal of Radiation Biology, 91(4), 329-335. https://doi.org/10.3109/09553002.2014.995381
21. Dick, L. R., & Fleming, P. E. (2010). Building on bortezomib: Second-generation proteasome inhibitors as anti-cancer therapy. Drug Discovery Today, 15(5-6), 243-249. https://doi.org/10.1016/j.drudis.2010.01.008
22. Tülüce, Y., Lak, P. T. A., Koyuncu, İ., Kılıç, A., Durgun, M., & Özkol, H. (2017). The apoptotic, cytotoxic and genotoxic effect of novel binuclear boron-fluoride complex on endometrial cancer. Biometals: An international Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine, 30(6), 933-944. https://doi.org/10.1007/s10534-017-0060-8
23. Suda, K., & Mitsudomi, T. (2014). Successes and limitations of targeted cancer therapy in lung cancer. In S. Peters & R. A. Stahel (Eds.), Successes and limitations of targeted cancer therapy (Progress in Tumor Research, Vol. 41, pp. 62–77). S. Karger AG. https://doi.org/10.1159/000355902
24. Rawla, P. (2019). Epidemiology of prostate cancer. World Journal of Oncology, 10(2), 63-89. https://doi.org/10.14740/wjon1191
25. Gallardo-Williams, M. T., Chapin, R. E., King, P. E., Moser, G. J., Goldsworthy, T. L., Morrison, J. P., & Maronpot, R. R. (2004). Boron supplementation inhibits the growth and local expression of IGF-1 in human prostate adenocarcinoma (LNCaP) tumors in nude mice. Toxicologic Pathology, 32(1), 73-78. https://doi.org/10.1080/01926230490260899
26. Mahabir, S., Spitz, M. R., Barrera, S. L., Dong, Y. Q., Eastham, C., & Forman, M. R. (2008). Dietary boron and hormone replacement therapy as risk factors for lung cancer in women. American Journal of Epidemiology, 167(9), 1070-1080. https://doi.org/10.1093/aje/kwn021
27. Thévenon, M. F., Tondi, G., & Pizzi, A. (2010). Friendly wood preservative system based on polymerized tannin resin-boric acid for outdoor applications. Maderas. Ciencia y tecnología, 12(3), 253-257. http://dx.doi.org/10.4067/S0718-221X2010000300009
28. Sayin, Z., Ucan, U. S., & Sakmanoglu, A. (2016). Antibacterial and antibiofilm effects of boron on different bacteria. Biological Trace Element Research, 173(1), 241-246. https://doi.org/10.1007/s12011-016-0637-z
29. Codina, R., Lockey, R. F., Diwadkar, R., Mobly, L. L., & Godfrey, S. (2003). Disodium octaborate tetrahydrate (DOT) application and vacuum cleaning, a combined strategy to control house dust mites. Allergy, 58(4), 318-324. https://doi.org/10.1034/j.1398-9995.2003.00100.x
30. Pratt, J. E., & Quill, K. (1996). A trial of disodium octaborate tetrahydrate for the control of Heterobasidion annosum. European Journal of Forest Pathology, 26(6), 297-305. https://doi.org/10.1111/j.1439-0329.1996.tb01075.x
31. Codina, R., Lockey, R. F., Diwadkar, R., Mobly, L. L., & Godfrey, S. (2003). Disodium octaborate tetrahydrate (DOT) application and vacuum cleaning, a combined strategy to control house dust mites. Allergy, 58(4), 318-324.
32. Sarac, N., Baygar, T., Ugur, A., Ceylan, O., & Boran, R. (2019, April 17-19). Determining the antimicrobial activity and wound healing capacity of disodium octaborate tetrahydrate [Conference presentation]. International Symposium on Boron, Nevşehir, Türkiye.
33. Gülerim, M. (2017). Development and characterization of antimicrobial gelatin and pectin films with boron derivatives (Thesis Number: 450550) [MSc. Thesis, Yeditepe University]. Council of Higher Education National Thesis Center.
34. Dalmizrak, A., Erbaykent Tepedelen, B., Ersoz, E., Celik, B., Korkmaz., M. (2018). Investigating the effects of boric acid and disodium octaborate tetrahydrate on cell dath in glioblastoma cell lines. [Conference presentation] 43rd FEBS Congress, Biochemistry Forever, Prague, Czech Republic. https://doi.org/10.1002/2211-5463.12453
35. Mosmann, T. (1983). Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Journal of Immunological Methods, 65(1-2), 55-63. https://doi.org/10.1016/0022-1759(83)90303-4
36. Abdul Ghafoor, N., Galatali, S., Yeniocak, S., Kaya, E., Sarac, N., & Ugur, A. (2022). Investigating anticancer potency of in vitro propagated endemic Thymus cilicicus Boiss. & Bal. extract on human lung, breast, and prostate cancer cell lines. Biologia, 77(11), 3229-3239. https://doi.org/10.1007/s11756-022-01168-7
37. Yeniocak, S., Galatalı, S., Demir, İ., Uğur, A., Saraç, N., & Kaya, E. (2025). Investigation of biological activities of in vitro grown Sesamum orientale plant extract on the cell cultures: Wound healing and antiproliferation. Advances in Traditional Medicine, 25(1), 233-246. https://doi.org/10.1007/s13596-024-00791-w
38. Justus, C. R., Leffler, N., Ruiz-Echevarria, M., & Yang, L. V. (2014). In vitro cell migration and invasion assays. Journal of visualized experiments: JoVE, (88), 51046.
39. Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of cancer: the next generation. Cell, 144(5), 646-674.
40. Valastyan, S., & Weinberg, R. A. (2011). Tumor metastasis: molecular insights and evolving paradigms. Cell, 147(2), 275-292.