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Boraks pentahidrat'ın glioblastoma multiforme hücre hattındaki tedavi potansiyelinin araştırılması

Yıl 2020, Cilt: 5 Sayı: 1, 56 - 61, 29.03.2020
https://doi.org/10.30728/boron.589644

Öz

Doğal ve sentetik bor bileşikleri ile yapılan son dönemdeki araştırmalar bu bileşiklerin kanserden korunma ve tedavisinde etkin olabileceğini işaret etmektedir. Bu bağlamda, sentetik bir bor bileşiği olan Boraks pentahidrat (BPH)’ın dördüncü evre beyin kanserini temsil eden glioblastoma multiforme (GBM) modeli U-87MG hücre hattı üzerindeki sitotoksik etkisi ile apoptoz ve otofaji indüksiyonu yönünden sınanması amaçlanmıştır. BPH’ın belirlenmiş IC50 dozu ile muamele edilmiş çalışma grubunun apoptoz ve otofaji oranlarındaki değişimler floresan temelli mikrokapiller sitometri cihazına uygun kitler (Muse® Annexin V & Hücre Ölümü ve Muse® Otofaji LC3-antikor temelli) aracılığı ile belirlenmiştir. Elde edilen veriler, GraphPad Prism 5 istatistik programı kullanılarak değerlendirilmiştir. Sitotosisite yönünden BPH’ın U-87 MG hücre hattındaki IC50 değeri 2454 μM olarak belirlenmiştir. Diğer taraftan kontrol grubuna oranla BPH ile muamele edilmiş grupta apoptoz oranı 12,79 kat iken otofaji oranının ise 1,2 kat arttığı saptanmıştır. Bu veriler ışığında, BPH’ın GBM’ye model oluşturan U-87 MG hücrelerine sitotoksik etkisi bilenirken, hücre ölümü biçiminin otofaji yerine apoptoz üzerinden gerçekleştiği anlaşılmaktadır. Bütün bunlarla birlikte, BPH’ın yeni araştırmalarla desteklenerek GBM tedavisinde kullanılabilecek alternatif bir ajan olabileceği düşünülmektedir.

Destekleyen Kurum

TÜBİTAK

Proje Numarası

113S700

Teşekkür

Teşekkür ederiz.

Kaynakça

  • [1] Mrugala M. M., Advances and challenges in the treatment of glioblastoma: A clinician's perspective, Discov. Med.,15 (83), 221-230, 2013.
  • [2] Krakstad C., Chekenya M., Survival signalling and apoptosis resistance in glioblastomas: Opportunities for targeted therapeutics, Mol. Cancer, 9, 135, 2010.
  • [3] Hubbard J. A, Binder D. K., Astrocytes and epilepsy chapter, 2 - Astrocytes in the mammalian brain, 39-51, 2016.
  • [4] Louis D. N., Perry A., Reifenberger G., Von Deimling A., Figarella-Branger D., Cavenee W. K., Ohgaki H., Wiestler O. D., Kleihues P., Ellison D. W., The 2016 world healt organization classification of tumors of the central nervous system: A summary, Acta Neuropathol., 131 (6), 803-20, 2016.
  • [5] Demirtaş A. Bor’un insan beslenmesi ve sağlığı açısından önemi, Atatürk Üniversitesi Ziraat Fakültesi Dergisi, 41 (1), 75-80, 2010.
  • [6] Bilgiç M., Dayık M., Borun özellikleri ve tekstil endüstrisinde kullanımıyla sağladığı avantajlar, Taşıt Teknolojileri Elektronik Dergisi 7(2), 2013.
  • [7] Murray F. J., A comparative review of the pharmacokinetics of boric acid in rodents and humans, Biol. Trace Elem. Res., 66, 331-41, 1998.
  • [8] Fail P. A., Chapin R. E., Price C. J., Heindel J. J., General, reproductive, developmental, and endocrine toxicity of boronated compounds, Reprod. Toxicol., 12 (1) 1-18, 1998.
  • [9] Naghii M. R., Mofid M., Asgari A. R., Hedayati M., Daneshpour M. S., Comparative effects of daily and weekly boron supplementation on plasma steroid hormones and proinflammatory cytokines, J. Trace Elem. Med. Biol., 25 (1), 54-58, 2011.
  • [10] Hakki S. S., Malkoc S., Dundar N., Kayis S. A., Hakki E. E., Hamurcu M., Dietary boron does not affect tooth strength, micro-hardness and density, but affect stooth mineral composition and alveolar bone mineral density in rabbits fed a high-energy diet, J. Trace Elem. Med. Biol., 29, 208-15 2015.
  • [11] Hakki S. S., Bozkurt B. S., Hakki E. E., Boron regulates mineralized tissue-associated proteins in osteoblasts (MC3T3-E1), J. Trace Elem. Med. Biol., 24, 243-50, 2010.
  • [12] Nzietchueng R. M., Dousset B., Franck P., Benderdour M., Nabet P., Hess K., Mechanism simplicated in the effects of boron on wound healing, J. Trace Elem. Med. Biol., 16 (4), 239-244 2002. [13] Tepedelen E. B., Soya E., Korkmaz M., Boric acid reduces the formation of DNA double strand breaks and accelerates wound healing process, Biol. Trace Elem. Res., 174 (2), 309-318, 2016.
  • [14] Hunt C. D., Herbel J. L., Boron affects energy metabolism in the streptozotocin-injected, Vitamin D~ 3-Deprived Rat., Magnesium and trace elements, 10, 374-374, 1991.
  • [15] Cui Y., Winton M. I., Zhang Z. F., Rainey C., Marshall J., De Kernion J. B., vd., Dietary boron intake and prostate cancer risk, Oncol. Rep., 11, 887–92, 2004.
  • [16] Korkmaz M., Uzgören E., Bakırdere S., Aydın F., Ataman O. Y., Effects of dietary boron on cervical cytopathology and on micro nucleus frequency in exfoliated buccal cells, Environ. Toxicol., 22, 17–25, 2007.
  • [17] Barranco W. T., Hudak P. F., Eckhert C. D., Evaluation of ecological and in vitro effects of boron on prostate cancer risk (United States), Cancer Causes Control, 18, 71–7, 2007.
  • [18] Tepedelen E. B., Korkmaz M., Tatlisumak E., Uluer E. T., Ölmez E., Değerli İ., Soya E., İnan S., A study on the anti carcinogenic effects of calcium fructoborate, Biol. Trace Elem. Res., 178 (2), 210-217, 2017.
  • [19] Thorburn A., ApoptosisandAutophagy: Regulatory connections between two supposedly different processes, Apoptosis, 13 (1), 1-9, 2008.
  • [20] Reed J. C., Dysregulation of apoptosis in cancer, Cancer J. Sci. Am., 4 (Suppl 1), S8–14, 1998.
  • [21] Sung B., Chung H. Y., Kim N.D., Role of apigenin in cancer prevention via the induction of apoptosis and autophagy, J. Cancer Prev., 21 (4), 216-226, 2016.
  • [22] Ding Q., Bao J., Zhao W., Hu Y., Lu J., Chen X., Natural autophagy regulators in cancer therapy: A review, Phytochem. Rev., 14 (1), 137–154, 2015.
  • [23] Bursch W., Oberhammer F. Schulte-Hermann R., Cell death by apoptosis and its protective role against disease, Trends Pharmacol. Sci., 13 (6), 245-51, 1992.
  • [24] Russo M., Russo G. L., Autophagy inducers in cancer, Biochem. Pharmacol., 2018.
  • [25] Barranco W. T., Eckhert C. D., Boric acid inhibits human prostate cancer cell proliferation, Cancer letters, 216 (1), 21-29, 2004.
  • [26] Kahraman E., Gürhan İ.D., Korkmaz M., Investigation of possible genotoxic and cytotoxic effects of differential boron compounds in ccl 62 (hela contaminant) human amniotic ephitelial cell line, Med. Sci., 2 (1), 2013.
  • [27] Murmu N., Ghosh P., Gomes A., Mitra S., Das M., Besra S. E., Majumdar J., Bhattacharya S., Sur P., Vedasiromoni J. R., Anti neoplastic effect of new boron compounds against leukemic cell lines and cells from leukemic patients, J. Exp. Clin. Cancer Res., CR, 20 (4), 511-515, 2002.
  • [28] Korkmaz M, Avcı C. B., Gündüz C., Aygüneş D., Erbaykent-Tepedelen B., Disodium pentaborate decahydrate (DPD) induced apoptosis by decreasing HTERT enzyme activity and disrupting F-actin organization of prostate cancer cells, Tumor Biology, 35 (2), 1531-1538, 2014.
  • [29] Cantürk Z., Tunali Y., Korkmaz S., Gülbaş Z., Cytotoxic and apoptotic effects of boron compounds on leukemia cell line, Cytotechnology, 68 (1), 87-93, 2016.
  • [30] Al-Ali R., Gonzalez-Sarmiento R., High concentrations of boric acid induce autophagy in cancer cell lines, BioRxiv, 193441, 2017.

Investigation of the therapy potential of borax pentahydrate in glioblastoma multiforme cell line

Yıl 2020, Cilt: 5 Sayı: 1, 56 - 61, 29.03.2020
https://doi.org/10.30728/boron.589644

Öz

Recent studies with natural and synthetic boron compounds suggest that these compounds may be effective in the prevention and treatment of cancer. In this context, a synthetic boron compound, Borax pentahydrate (BPH), is aimed to be tested for cytotoxic effect on the glioblastoma multiforme (GBM) model U-87MG cell line representing fourth stage brain cancer in terms of induction of apoptosis and autophagy. Changes in apoptosis and autophagy rates of the research group treated with the specified IC50 dose of BPH were determined by fluorescence-based microcapillary cytometry kit (Muse® Annexin V & Cell Death and Muse® Autophagy LC3-antibody based kit). The data obtained were evaluated using GraphPad Prism 5 statistical program. The IC50 value of BPH in the U-87MG cell line was determined to be 2454μM for cytotoxicity. On the other hand, apoptosis rate was determined as increased 12.79 folds in the BPH treated group compared to the control group, while elevation of autophagy rate is determined as 1.2 folds. In the light of these data, while the cytotoxic effect of BPH on U-87MG cells, which is a model for GBM, is designated, it is understood that cell death pattern occurs through apoptosis instead of autophagy. In addition to these, it is thought that with the support of other new studies BPH may be an alternative agent that can be used in the treatment of GBM.

Proje Numarası

113S700

Kaynakça

  • [1] Mrugala M. M., Advances and challenges in the treatment of glioblastoma: A clinician's perspective, Discov. Med.,15 (83), 221-230, 2013.
  • [2] Krakstad C., Chekenya M., Survival signalling and apoptosis resistance in glioblastomas: Opportunities for targeted therapeutics, Mol. Cancer, 9, 135, 2010.
  • [3] Hubbard J. A, Binder D. K., Astrocytes and epilepsy chapter, 2 - Astrocytes in the mammalian brain, 39-51, 2016.
  • [4] Louis D. N., Perry A., Reifenberger G., Von Deimling A., Figarella-Branger D., Cavenee W. K., Ohgaki H., Wiestler O. D., Kleihues P., Ellison D. W., The 2016 world healt organization classification of tumors of the central nervous system: A summary, Acta Neuropathol., 131 (6), 803-20, 2016.
  • [5] Demirtaş A. Bor’un insan beslenmesi ve sağlığı açısından önemi, Atatürk Üniversitesi Ziraat Fakültesi Dergisi, 41 (1), 75-80, 2010.
  • [6] Bilgiç M., Dayık M., Borun özellikleri ve tekstil endüstrisinde kullanımıyla sağladığı avantajlar, Taşıt Teknolojileri Elektronik Dergisi 7(2), 2013.
  • [7] Murray F. J., A comparative review of the pharmacokinetics of boric acid in rodents and humans, Biol. Trace Elem. Res., 66, 331-41, 1998.
  • [8] Fail P. A., Chapin R. E., Price C. J., Heindel J. J., General, reproductive, developmental, and endocrine toxicity of boronated compounds, Reprod. Toxicol., 12 (1) 1-18, 1998.
  • [9] Naghii M. R., Mofid M., Asgari A. R., Hedayati M., Daneshpour M. S., Comparative effects of daily and weekly boron supplementation on plasma steroid hormones and proinflammatory cytokines, J. Trace Elem. Med. Biol., 25 (1), 54-58, 2011.
  • [10] Hakki S. S., Malkoc S., Dundar N., Kayis S. A., Hakki E. E., Hamurcu M., Dietary boron does not affect tooth strength, micro-hardness and density, but affect stooth mineral composition and alveolar bone mineral density in rabbits fed a high-energy diet, J. Trace Elem. Med. Biol., 29, 208-15 2015.
  • [11] Hakki S. S., Bozkurt B. S., Hakki E. E., Boron regulates mineralized tissue-associated proteins in osteoblasts (MC3T3-E1), J. Trace Elem. Med. Biol., 24, 243-50, 2010.
  • [12] Nzietchueng R. M., Dousset B., Franck P., Benderdour M., Nabet P., Hess K., Mechanism simplicated in the effects of boron on wound healing, J. Trace Elem. Med. Biol., 16 (4), 239-244 2002. [13] Tepedelen E. B., Soya E., Korkmaz M., Boric acid reduces the formation of DNA double strand breaks and accelerates wound healing process, Biol. Trace Elem. Res., 174 (2), 309-318, 2016.
  • [14] Hunt C. D., Herbel J. L., Boron affects energy metabolism in the streptozotocin-injected, Vitamin D~ 3-Deprived Rat., Magnesium and trace elements, 10, 374-374, 1991.
  • [15] Cui Y., Winton M. I., Zhang Z. F., Rainey C., Marshall J., De Kernion J. B., vd., Dietary boron intake and prostate cancer risk, Oncol. Rep., 11, 887–92, 2004.
  • [16] Korkmaz M., Uzgören E., Bakırdere S., Aydın F., Ataman O. Y., Effects of dietary boron on cervical cytopathology and on micro nucleus frequency in exfoliated buccal cells, Environ. Toxicol., 22, 17–25, 2007.
  • [17] Barranco W. T., Hudak P. F., Eckhert C. D., Evaluation of ecological and in vitro effects of boron on prostate cancer risk (United States), Cancer Causes Control, 18, 71–7, 2007.
  • [18] Tepedelen E. B., Korkmaz M., Tatlisumak E., Uluer E. T., Ölmez E., Değerli İ., Soya E., İnan S., A study on the anti carcinogenic effects of calcium fructoborate, Biol. Trace Elem. Res., 178 (2), 210-217, 2017.
  • [19] Thorburn A., ApoptosisandAutophagy: Regulatory connections between two supposedly different processes, Apoptosis, 13 (1), 1-9, 2008.
  • [20] Reed J. C., Dysregulation of apoptosis in cancer, Cancer J. Sci. Am., 4 (Suppl 1), S8–14, 1998.
  • [21] Sung B., Chung H. Y., Kim N.D., Role of apigenin in cancer prevention via the induction of apoptosis and autophagy, J. Cancer Prev., 21 (4), 216-226, 2016.
  • [22] Ding Q., Bao J., Zhao W., Hu Y., Lu J., Chen X., Natural autophagy regulators in cancer therapy: A review, Phytochem. Rev., 14 (1), 137–154, 2015.
  • [23] Bursch W., Oberhammer F. Schulte-Hermann R., Cell death by apoptosis and its protective role against disease, Trends Pharmacol. Sci., 13 (6), 245-51, 1992.
  • [24] Russo M., Russo G. L., Autophagy inducers in cancer, Biochem. Pharmacol., 2018.
  • [25] Barranco W. T., Eckhert C. D., Boric acid inhibits human prostate cancer cell proliferation, Cancer letters, 216 (1), 21-29, 2004.
  • [26] Kahraman E., Gürhan İ.D., Korkmaz M., Investigation of possible genotoxic and cytotoxic effects of differential boron compounds in ccl 62 (hela contaminant) human amniotic ephitelial cell line, Med. Sci., 2 (1), 2013.
  • [27] Murmu N., Ghosh P., Gomes A., Mitra S., Das M., Besra S. E., Majumdar J., Bhattacharya S., Sur P., Vedasiromoni J. R., Anti neoplastic effect of new boron compounds against leukemic cell lines and cells from leukemic patients, J. Exp. Clin. Cancer Res., CR, 20 (4), 511-515, 2002.
  • [28] Korkmaz M, Avcı C. B., Gündüz C., Aygüneş D., Erbaykent-Tepedelen B., Disodium pentaborate decahydrate (DPD) induced apoptosis by decreasing HTERT enzyme activity and disrupting F-actin organization of prostate cancer cells, Tumor Biology, 35 (2), 1531-1538, 2014.
  • [29] Cantürk Z., Tunali Y., Korkmaz S., Gülbaş Z., Cytotoxic and apoptotic effects of boron compounds on leukemia cell line, Cytotechnology, 68 (1), 87-93, 2016.
  • [30] Al-Ali R., Gonzalez-Sarmiento R., High concentrations of boric acid induce autophagy in cancer cell lines, BioRxiv, 193441, 2017.
Toplam 29 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Mühendislik
Bölüm Research Makaleler
Yazarlar

Burak Çelik Bu kişi benim

Ezgi Ersöz Bu kişi benim

Mehmet Korkmaz 0000-0003-1058-5586

Proje Numarası 113S700
Yayımlanma Tarihi 29 Mart 2020
Kabul Tarihi 24 Mart 2020
Yayımlandığı Sayı Yıl 2020 Cilt: 5 Sayı: 1

Kaynak Göster

APA Çelik, B., Ersöz, E., & Korkmaz, M. (2020). Boraks pentahidrat’ın glioblastoma multiforme hücre hattındaki tedavi potansiyelinin araştırılması. Journal of Boron, 5(1), 56-61. https://doi.org/10.30728/boron.589644

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