Mehmet Dinçer BİLGİN, Ayşe ÇİĞEL, Rauf Onur EK

Kolon Kanseri Hücrelerinde Borik Asidin Anti-kanser ve Biyolojik Etkilerinin Değerlendirilmesi

Amaç: Borun biyolojideki rolü, gen ekspresyonunun koordineli düzenlenmesini ve tüm canlı organizmaların büyümesini ve çoğalmasını içerir. Borik asidin kanser hücrelerinin çoğalmasını düzenlediği bilinmektedir. Kolon kanseri, erkeklerde ve kadınlarda yüksek mortaliteye sahip kanser türleri arasındadır. Bu çalışmanın amacı, borik asidin plazmada formu olan borik asidin Caco-2 kolorektal kanser hücreleri üzerindeki etkilerini değerlendirmektir. Gereç ve Yöntemler: İlk olarak, Caco-2 insan kolon kanseri hücrelerinde borik asidin (0 ila 1 mM) hücre proliferasyonuna aktivitesini belirlenmiş daha sonra ve Western Blot ve SDS PAGE analizi kullanılarak Caspase-3 ve BCL-2 protein düzeyleri değerlendirilmiştir. Bulgular: Sonuçlarımız, borik asidin Caco-2 kanser hücrelerinin çoğalmasını doza bağımlı bir şekilde inhibe ettiğini göstermiştir. Ayrıca, borik asit konsantrasyonu arttıkça BCL-2 protein ekspresyonunun azalttığı saptanmıştır. Sonuç: Bu araştırma borik asidin Caco-2 kanser hücrelerine karşı anti-kanser etkilerini gösteren ilk çalışmadır. Borik asidin anti-kanser mekanizmasını açıklamak için ileri moleküler teknikleri kullanan çalışmalara ihtiyaç vardır.

Evaluation of the Anti-cancer and Biological Effects of Boric Acid on Colon Cancer Cell Line

Objective: The role of boron in biology includes the coordinated regulation of geneexpression as well as the growth and proliferation of all living organisms. Boric acidis known to regulate the proliferation of cancer cells. Colon cancer is among thetypes of cancer with a high rate of mortality in both men and women. The aim ofthis study is to evaluate the effects of boric acid (the dominant of boron in plasma)on Caco-2 colorectal cancer cell line.Materials and Methods: Firstly, the cytotoxic effect of boric acid (0 to 1 mM) onCaco-2 human colon cancer cells was determined and the expressions of Caspase-3 and BCL-2 were evaluated using Western Blot and sodium dodecyl sulphatepolyacrylamide gel electrophoresis analysis.Results: Our results showed that boric acid inhibits the proliferation Caco-2cancer cells in a dose dependent manner. We also demonstrated that BCL-2 proteinexpression decreased with increasing concentrations of boric acid.Conclusion: This is the first study that demonstrates the anti-cancer effects ofboric acid against Caco-2 cancer cell line. Further studies using advanced moleculartechniques are needed to precisely explain the anti-cancer mechanisms of boricacid.

PDF

___

1. Midgley R, Kerr D. Colorectal cancer. Lancet 1999; 353: 391-9.
2. Sugarbaker PH. Successful management of microscopic residual disease in large bowel cancer. Cancer Chemother Pharmacol 1999; 43 (Suppl): S15-25.
3. Argust P. Distribution of boron in the environment. Biol Trace Element Res 1998; 66: 131-43.
4. Price CJ, Strong PL, Murray FJ, Goldberg MM. Blood boron concentrations in preggnant rads fed boric acid throughout gestation. Repord Toxicol 1997; 11: 833-42.
5. Murray FJ. A comparative review of the pharmacokinetics of boric acid in rodents and humans. Biol Trace Element Res 1998; 66: 331-41.
6. Moseman RF. Chemical disposition of boron in animals and humans. Environ Health Perspect 1994; 102 (Suppl 7): 113-7.
7. Rowe R, Eckhert C. Boron is required for zebrafish embrogenesis. J Exp Biol 2004; 202: 21-9.
8. Kelly GS. Boron: a review of its nutritional interactions and therapeutic uses. Altern Med Rev 1997; 2: 48-56.
9. Hunt CD, Idso JP. Dietary boron as a physiological regulator of the normal inflammatory response: a review and current research progress. J Trace Elem Exp Med 1999; 12: 221-3.
10. Barranco WT, Hudak PF, Eckhert CD. Evaluation of ecological and in vitro effects of boron on prostate cancer risk (United States). Cancer Causes Control 2007; 18: 71-7.
11. Albuz Ö, Dülger D, Tunali BÇ, Aydin F, Yalçin S, Türk M. Effects of B2O3 (boron trioxide) on colon cancer cells: our first-step experience and in vitro results. Turk J Biol 2019; 43: 209-23.
12. Barranco WT, Eckhert CD. Boric acid inhibits human prostate cancer cell proliferation. Cancer Lett 2004; 216: 21-9.
13. Hacioglu C, Kar F, Kacar S, Sahinturk V, Kanbak G. 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 2020; 193: 400-9.
14. Gallardo-Williams MT, Chapin RE, King PE, Moser GJ, Goldsworthy TL, Morrison JP, et al. Boron supplementation inhibits the growth and local expression of IGF-1 in human prostate adenocarcinoma (LNCaP) Tumors in nude mice. Toxicol Pathol 2004; 32: 73-8.
15. Korkmaz M, Uzgören E, Bakirdere S, Aydin F, Ataman OY. Effects of dietary boron on cervical cytopathology and on micronucleus frequency in exfoliated buccal cells. Environ Toxicol 2007; 22: 17-25.
16. Meacham SL, Elwell KE, Ziagler S, Carper SW. Boric acid inhibits cell growth in breast and prostate cancer cell lines. Advance in Plant and Animal Boron Nutrution. Xu F, Heiner E. Goldbach HE, Bell RW, Brown PH, Fujiwara T, et al. editors. Switzerland: Spinger; 2007; 299-306.
17. Barranco WT, Kim DH, Stella Jr SL, Eckhert CD. Boric acid inhibits stored Ca2+ release in DU-145 prostate cancer cells. Cell Biol Toxicol 2009; 25: 309-20.
18. Barranco WT, Eckhert CD. Cellular changes in boric acid-treated DU-145 prostate cancer cells. Br J Cancer 2006; 94: 884-90.
19. Acerbo AS, Miller LM. Assessment of the chemical changes induced in human melanoma cells by boric acid treatment using infrared imaging. Analyst 2009; 134: 1669-74.
20. Scorei R, Ciubar R, Ciofrangeanu CM, Mitran V, Cimpean A, Iordachescu D. Comparative effects of boric acid and calcium fructoborate on breast cancer cells. Biol Trace Elem Res 2008; 122: 197-205.
21. Rudner J, Jendrossek V, Belka C. New sights in the role of Bcl-2. Bcl-2 and endoplasmic reticulum. Apoptosis 2002; 7: 441-7.