Boric acid as a promising agent in the treatment of ovarian cancer: Molecular mechanisms

Çabuş, Ümit; Seçme, Mücahit; Kabukçu, Cihan; Çil, Nazlı; Dodurga, Yavuz; Mete, Gülçin Abban; Fenkci, Ibrahim Veysel

doi:10.1016/j.gene.2021.145799

Cited by 12 publications

(4 citation statements)

References 51 publications

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“…Conversely, in the study conducted by Kahraman and Göker, it was observed that BA led to an increase in apoptosis and autophagy, inhibited cell viability, and diminished migration in hepatocellular carcinoma cells [ 16 ]. In a similar vein, it has been indicated that BA hinders cell proliferation, invasion, migration, and colony formation in ovarian cancer cells, while concurrently promoting apoptosis and inducing oxidative stress [ 17 ]. In line with prior research, our study demonstrated for the first time that in endometrial cancer BA led to a significant reduction in cell survival, and this observed effect was contingent on the dosage administered, with an IC50 value of 40 mM.…”

Section: Discussionmentioning

confidence: 99%

Boric Acid Exhibits Anticancer Properties in Human Endometrial Cancer Ishikawa Cells

Çakır Gündoğdu,

Arı,

Höbel

et al. 2023

Cureus

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Objective This study aims to explore the potential anti-cancer properties of boric acid (BA) in human endometrial cancer Ishikawa cells by assessing its influence on cell viability, apoptosis, oxidative stress, and inflammatory responses. Methods The impact of BA at concentrations ranging from 2.5 to 100 mM on cell viability was assessed in Ishikawa cells and normal fibroblast L929 cells (used as the control) through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Spectrophotometric measurements were performed to determine the total oxidant status (TOS) and total antioxidant status (TAS) in BA-treated cells, and the oxidative stress index (OSI) was calculated. The enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of cytochrome c and caspase 3, both of which are constituents of the extrinsic apoptotic pathway. Furthermore, changes in the concentrations of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) in the cells were analyzed using ELISA and immunofluorescence staining. Results The exposure of Ishikawa cells to BA for 24 hours led to a dose-dependent decline in cell viability, with an IC 50 value of 40 mM. BA dose-dependently increased cytochrome c and caspase 3 levels in cancer cells. In Ishikawa cells, BA treatment led to a significant elevation in OSI. Moreover, the concentrations of TNF-α and IL-1β exhibited a dose-dependent decrease in BA-treated cells. On the other hand, in L929 cells, BA decreased OSI in a dose-dependent manner but did not change TNF-α and IL-1β levels. Concentrations up to 80 mM had no effect on cell viability and apoptosis, but BA at 80 mM concentration decreased viability and increased cytochrome c and caspase 3 levels in L929 cells. Conclusion BA inhibited cell viability, triggered apoptosis, induced oxidative stress, and suppressed inflammatory responses in endometrial cancer cells. Notably, at its IC 50 concentration, BA had no cytotoxic effect on normal fibroblasts. Given its favorable properties, BA may provide a valuable therapeutic option to impede the development and progression of endometrial cancer.

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Section: Discussionmentioning

confidence: 99%

Boric Acid Exhibits Anticancer Properties in Human Endometrial Cancer Ishikawa Cells

Çakır Gündoğdu,

Arı,

Höbel

et al. 2023

Cureus

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“…BA was shown to modulate MAPKs 19 as well as Nrf2 3 signaling pathways, and the levels of intracellular GSH and selected antioxidant enzymes were reported to be alternatively decreased 5 or increased 13 upon BA exposure. As regard the mechanism of cell growth inhibition, a cell death‐independent inhibition of proliferation 6,9 or an induction of apoptotic cell death 5,22 was alternatively proposed. Such conflicting effects described for pharmacological BA concentrations likely result from a balance of mechanisms associated with irreversible cell injury and death vs. reversible cell injury and adaptation.…”

Section: Discussionmentioning

confidence: 99%

Enhancement of ferroptosis by boric acid and its potential use as chemosensitizer in anticancer chemotherapy

et al. 2022

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Ferroptosis is a form of regulated cell death (RCD) characterized by intracellular iron ion accumulation and reactive oxygen species (ROS)-induced lipid peroxidation. Ferroptosis in cancer and ferroptosis-related anticancer drugs have recently gained interest in the field of cancer treatment. Boron is an essential trace element playing an important role in several biological processes. Recent studies have described contrasting effects of boric acid (BA) in cancer cells, ranging from protective/mitogenic to damaging/antiproliferative. Interestingly, boron has been shown to interfere with critical factors involved in ferroptosis-intracellular glutathione and lipid peroxidation in the first place.Thus, the present study was aimed to verify the ability of boron to modulate the ferroptotic process in HepG2 cells, a model of hepatocellular carcinoma.Our results indicate that-when used at high, pharmacological concentrations-BA can increase intracellular ROS, glutathione, and TBARS levels, and enhance ferroptosis induced by RSL3 and erastin. Also, high BA concentrations can directly induce ferroptosis, and such BA-induced ferroptosis can add to the cytotoxic effects of anticancer drugs sorafenib, doxorubicin and cisplatin. These observations suggest that BA could be exploited as a chemo-sensitizer agent in order to overcome cancer drug resistance in selected conditions. However, the possibility of reaching suitably high concentrations of BA in the tumor microenvironment will need to be further investigated.

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“…Kahraman ve Göker tarafından yapılan çalışmada ise borik asidin hepatoselüler karsinom hücrelerinde apoptoz ve otofajiyi artırdığı, hücre canlılığını inhibe ettiği ve migrasyonu azalttığı gözlenmiştir (26). Benzer şekilde, borik asidin yumurtalık kanseri hücrelerinde hücre çoğalmasını, istilasını, göçünü ve koloni oluşumunu engellerken aynı zamanda apoptozu teşvik ettiği ve oksidatif stresi indüklediği gösterilmiştir (27). Önceki araştırmalara paralel olarak, çalışmamız borik asidin U251 hücrelerindeki hücre sağ kalımında önemli bir azalmaya yol açtığını ve gözlenen bu etkinin, 312,7 μM'lık bir IC50 değeriyle uygulanan doza bağlı olduğunu gösterdi.…”

Section: Tartışma Ve Sonuçunclassified

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

HACIOĞLU

2024

Osmangazi̇ Journal of Medicine

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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.

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Boric acid as a promising agent in the treatment of ovarian cancer: Molecular mechanisms

Cited by 12 publications

References 51 publications

Boric Acid Exhibits Anticancer Properties in Human Endometrial Cancer Ishikawa Cells

Boric Acid Exhibits Anticancer Properties in Human Endometrial Cancer Ishikawa Cells

Enhancement of ferroptosis by boric acid and its potential use as chemosensitizer in anticancer chemotherapy

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

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