Antiproliferative Effects of Boric Acid on Glioblastoma Cells via Endoplasmic Reticulum Stress-Related Proteins

Year 2024, Volume: 46 Issue: 2, 217 - 227, 18.03.2024

Ceyhan Hacıoğlu

https://doi.org/10.20515/otd.1404026

Abstract

Endoplasmic reticulum (ER) stress is involved in the regulation of metabolic homeostasis and the pathophysiology of various cancers, including gliomas. Boron, a trace element for humans, has demonstrated potential anti-cancer properties in experimental and epidemiological studies. This study aims to investigate the effects of boric acid on cell viability, apoptosis and oxidant status via ER stress signaling in human glioblastoma (GBM) cells. The study evaluated the cytotoxic effect of boric acid (0–1600 µM) on U251 cell viability using MTT assay. Spectrophotometric measurements were performed to determine the levels of GRP78, ATF4, CHOP, cytochrome c, caspase 3, caspase 12, total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI) in boric acid-treated cells. Exposure of U251 cells to boric acid caused a concentration- and time-dependent decrease in cell viability. According to MTT analysis, the IC50 values of boric acid at 24, 48 and 72 hours were determined as 312.7 μM, 208.6 μM and 115.2 μM, respectively. Boric acid concentration-dependently increased the levels of cytochrome c, caspase 3 and caspase 12 in U251 cells. In U251 cells, cytochrome c levels increased approximately 3-fold, caspase 3 levels increased approximately 2-fold, and caspase 12 levels increased approximately 2-fold at a boric acid concentration of 312.7 μM. Additionally, boric acid treatment significantly increased TOS and OSI in U251 cells. Furthermore, GRP78 and ATF4 levels showed a concentration-dependent decrease in boric acid-treated cells. Conversely, boric acid increased CHOP levels in U251 cells in a concentration-dependent manner. In summary, boric acid induced apoptosis and oxidative stress by triggering ER stress in GBM cells. With these positive properties, boric acid may be a potential therapeutic agent in the treatment of GBM.

Keywords

Boric acid, ER stress, Glioblastoma

Borik Asidin Endoplazmik Retikulum Stresiyle İlgili Proteinler Aracılığıyla Glioblastoma Hücreleri Üzerindeki Antiproliferatif Etkileri

Abstract

Endoplazmik retikulum (ER) stresi, metabolizma homeostazının düzenlenmesinde ve gliomalar dahil çeşitli kanserlerin fizyopatolojisinde rol alır. İnsanlar için eser element olan bor, deneysel ve epidemiyolojik çalışmalarda potansiyel kanser karşıtı özellikler göstermiştir. Bu çalışma, borik asidin insan glioblastoma (GBM) hücrelerindeki ER stresi sinyalizasyonuyla hücre canlılığı, apoptoz ve oksidan durum üzerindeki etkilerini araştırmayı amaçlamaktadır. Çalışma, MTT analizi kullanılarak borik asidin (0-1600 µM) U251 hücre canlılığı üzerindeki sitotoksik etkisini değerlendirdi. Borik asitle tedavi edilen hücrelerde GRP78, ATF4, CHOP, sitokrom c, kaspaz 3, kaspaz 12, toplam oksidan durum (TOS), toplam antioksidan durum (TAS) ve oksidatif stres indeksi (OSI) seviyelerini belirlemek için spektrofotometrik ölçümler yapıldı. U251 hücrelerinin borik aside maruz bırakılması, hücre canlılığında konsantrasyon ve zaman bağımlı bir düşüşe neden oldu. MTT analizi göre, borik asidin 24, 48 ve 72 saat IC50 sırasıyla değerleri 312,7 μM, 208,6 μM ve 115,2 μM olarak belirlendi. Borik asit, U251 hücrelerinde sitokrom c, kaspaz 3 ve kaspaz 12 düzeylerini konsantrasyona bağlı olarak arttırdı. U251 hücrelerinde sitokrom c seviyeleri yaklaşık 3 katlık, kaspaz 3 seviyeleri yaklaşık 2 katlık ve kaspaz 12 seviyeleri yaklaşık 2 katlık artışla 312,7 μM borik asit konsantrasyonunda tespit edilmiştir. Ek olarak borik asit tedavisi, U251 hücrelerinde TOS ve OSI'yi önemli ölçüde artırdı. Ayrıca, GRP78 ve ATF4 seviyeleri borik asitle tedavi edilen hücrelerde konsantrasyona bağlı bir azalma gösterdi. Tersine borik asit, U251 hücrelerinde CHOP seviyelerini konsantrasyona bağlı bir şekilde arttırdı. Özetle, borik asit GBM hücrelerinde ER stresini tetikleyerek apoptozu ve oksidatif stresi indükledi. Bu olumlu özellikleriyle borik asit, GBM'nin tedavisinde potansiyel bir terapötik ajan olabilir.

Keywords

Borik asit, ER stresi, Glioblastoma

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