Cytotoxic Effects of Borax via GPx4/ACSL4 Signaling Pathway in Colorectal Cancer Cells

Ceyhan Hacıoğlu; Fatih Davran

Makale detayları

Cytotoxic Effects of Borax via GPx4/ACSL4 Signaling Pathway in Colorectal Cancer Cells

Yazarlar:

Ceyhan Hacıoğlu | Fatih Davran

Yayıncı:

Duzce University

Ana Başlıklar:

Klinik Tıp Bilimleri

Dergi:

Sağlık Bilimlerinde Değer Vol.13 Issue 1, pp.54-60

Belge Tipi:

Makale

Yayın Tarihi:

1/2023

Belge Dili:

Türkçe

Document ID (Org No.):

2001281924

pISSN:

2792-0542

Anahtar kelimeler:

Özet:

 Aim: Colorectal cancer CRC ranks third in terms of malignancy and second in cancer-related deaths, accounting for approximately 10 of cancer-related deaths. Ferroptosis is a potential iron-induced cell death pathway that could increase the anti-cancer efficacy of therapeutics in preventing drug resistance in the treatment of many cancers, including CRC. In this study, we aimed to investigate the anti-proliferative effects of borax via ferroptosis signaling pathway in CRC cells. Material and Methods: Firstly, we determined the cytotoxic concentrations of borax range 0 to 64 mM with the 3-4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide MTT assay. Subsequently, glutathione peroxidase 4 GPx4, acyl-CoA synthetase long chain family member 4 ACSL4, malondialdehyde MDA and 8-hydroxydeoxyguanosine 8-OHdG levels were determined in HCT-116 cells incubated with cytotoxic borax concentrations for 24 hours. Results: Borax at 1 and 4 mM concentrations did not affect cell viability, while borax at 8 mM and above concentrations significantly reduced viability in HTC-116 cells p0.05. According to MTT results, IC25 and IC50 concentrations of borax were determined as 12.5 mM and 20.8 mM, respectively. In HTC-116 cells, exposure to 12.5, 16.2, and 20.8 mM borax for 24 hours resulted in a concentration-dependent decrease in GPx4 levels and an increase in ACSL4 levels. We also found that increased borax administration to HTC-116 cells caused lipid peroxidation and DNA damage with a significant increase in MDA and 8-OHdG levels compared to control p0.05. Conclusion: In line with our experimental data, borax showed anti-proliferative effects by inducing ferroptosis as a potential anti-cancer agent in human CRC cells.

 Aim: Colorectal cancer CRC ranks third in terms of malignancy and second in cancer-related deaths, accounting for approximately 10 of cancer-related deaths. Ferroptosis is a potential iron-induced cell death pathway that could increase the anti-cancer efficacy of therapeutics in preventing drug resistance in the treatment of many cancers, including CRC. In this study, we aimed to investigate the anti-proliferative effects of borax via ferroptosis signaling pathway in CRC cells. Material and Methods: Firstly, we determined the cytotoxic concentrations of borax range 0 to 64 mM with the 3-4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide MTT assay. Subsequently, glutathione peroxidase 4 GPx4, acyl-CoA synthetase long chain family member 4 ACSL4, malondialdehyde MDA and 8-hydroxydeoxyguanosine 8-OHdG levels were determined in HCT-116 cells incubated with cytotoxic borax concentrations for 24 hours. Results: Borax at 1 and 4 mM concentrations did not affect cell viability, while borax at 8 mM and above concentrations significantly reduced viability in HTC-116 cells p0.05. According to MTT results, IC25 and IC50 concentrations of borax were determined as 12.5 mM and 20.8 mM, respectively. In HTC-116 cells, exposure to 12.5, 16.2, and 20.8 mM borax for 24 hours resulted in a concentration-dependent decrease in GPx4 levels and an increase in ACSL4 levels. We also found that increased borax administration to HTC-116 cells caused lipid peroxidation and DNA damage with a significant increase in MDA and 8-OHdG levels compared to control p0.05. Conclusion: In line with our experimental data, borax showed anti-proliferative effects by inducing ferroptosis as a potential anti-cancer agent in human CRC cells.

 Aim: Colorectal cancer CRC ranks third in terms of malignancy and second in cancer-related deaths, accounting for approximately 10 of cancer-related deaths. Ferroptosis is a potential iron-induced cell death pathway that could increase the anti-cancer efficacy of therapeutics in preventing drug resistance in the treatment of many cancers, including CRC. In this study, we aimed to investigate the anti-proliferative effects of borax via ferroptosis signaling pathway in CRC cells. Material and Methods: Firstly, we determined the cytotoxic concentrations of borax range 0 to 64 mM with the 3-4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide MTT assay. Subsequently, glutathione peroxidase 4 GPx4, acyl-CoA synthetase long chain family member 4 ACSL4, malondialdehyde MDA and 8-hydroxydeoxyguanosine 8-OHdG levels were determined in HCT-116 cells incubated with cytotoxic borax concentrations for 24 hours. Results: Borax at 1 and 4 mM concentrations did not affect cell viability, while borax at 8 mM and above concentrations significantly reduced viability in HTC-116 cells p0.05. According to MTT results, IC25 and IC50 concentrations of borax were determined as 12.5 mM and 20.8 mM, respectively. In HTC-116 cells, exposure to 12.5, 16.2, and 20.8 mM borax for 24 hours resulted in a concentration-dependent decrease in GPx4 levels and an increase in ACSL4 levels. We also found that increased borax administration to HTC-116 cells caused lipid peroxidation and DNA damage with a significant increase in MDA and 8-OHdG levels compared to control p0.05. Conclusion: In line with our experimental data, borax showed anti-proliferative effects by inducing ferroptosis as a potential anti-cancer agent in human CRC cells.

 Amaç: Kolorektal kanser CRC, kansere bağlı ölümlerin yaklaşık 10unu oluşturmasıyla, malignite yönünden üçüncü ve kansere bağlı ölümlerde ikinci sırada yer almaktadır. Ferroptoz, CRC dahil çok sayıda kanserin tedavisinde ilaç direncini önlemede terapötiklerin anti-kanser etkinliğini arttırabilecek potansiyel demire bağlı hücre ölüm yolağıdır. Bu çalışmada CRC hücrelerinde ferroptozu sinyal yolağı üzerinden boraksın anti-proliferatif etkilerini araştırmak amaçlandı. Gereç ve Yöntemler: Öncelikle, boraksın sitotoksik konsantrasyonları 0-64 mM aralığında 3-4,5-dimetiltiazol-2-il-2,5-difenil tetrazolyum bromür MTT testi ile belirlendi. Daha sonra sitotoksik boraks konsantrasyonları ile 24 saat inkübe edilen HCT-116 hücrelerinde glutatyon peroksidaz 4 GPx4, açil-KoA sentetaz uzun zincirli aile üyesi 4 ACSL4, malondialdehit MDA ve 8-hidroksideoksiguanozin 8-OHdG seviyeleri belirlendi. Bulgular: 1 ve 4 mM boraks konsantrasyonları hücre canlılığını etkilemezken, 8 mM ve üzerindeki boraks konsantrasyonları HTC-116 hücrelerinde canlılığı anlamlı şekilde düşürmüştür p0,05. MTT sonuçlarına göre, boraksın IC25 ve IC50 konsantrasyonları sırasıyla 12,5 mM ve 20,8 mM olarak belirlendi. HTC-116 hücrelerinde 24 saat boyunca 12.5, 16,2 ve 20,8 mM boraks maruziyeti GPx4 seviyelerinde konsantrasyon bağlım şekilde düşüş olurken, ACSL4 seviyelerinde artış olmuştur. Ayrıca, HTC-116 hücrelerine artan boraks uygulamasının, kontrole kıyasla MDA ve 8-OHdG seviyelerinde önemli bir artış ile lipit peroksidasyonuna ve DNA hasarına neden olduğu bulundu p0,05. Sonuç: Deneysel verilerimiz doğrultusunda, boraks insan CRC hücrelerinde potansiyel bir anti-kanser ajanı olarak ferroptozu indükleyerek anti-proliferatif etkiler göstermiştir.

Makale detayları

Cytotoxic Effects of Borax via GPx4/ACSL4 Signaling Pathway in Colorectal Cancer Cells

Yazarlar:

Ceyhan Hacıoğlu | Fatih Davran

Yayıncı:

Duzce University

Ana Başlıklar:

Klinik Tıp Bilimleri

Dergi:

Sağlık Bilimlerinde Değer Vol.13 Issue 1, pp.54-60

Belge Tipi:

Makale

Yayın Tarihi:

1/2023

Belge Dili:

Türkçe

Document ID (Org No.):

2001281924

pISSN:

2792-0542

Borax

DNA damage

ferroptosis

HTC-116

lipid peroxidation

Boraks

DNA hasarı

ferroptoz

HTC-116

lipit peroksidasyonu

Sayı

Makale detayları

Yazarlar: Ceyhan Hacıoğlu | Fatih Davran

Yayıncı: Duzce University

Ana Başlıklar: Klinik Tıp Bilimleri

Dergi: Sağlık Bilimlerinde Değer Vol.13 Issue 1, pp.54-60

Belge Tipi: Makale

Yayın Tarihi: 1/2023

Belge Dili: Türkçe

Document ID (Org No.): 2001281924

pISSN: 2792-0542

Sayı

Yazarlar:

Ceyhan Hacıoğlu | Fatih Davran

Yayıncı:

Duzce University

Ana Başlıklar:

Klinik Tıp Bilimleri

Dergi:

Sağlık Bilimlerinde Değer Vol.13 Issue 1, pp.54-60

Belge Tipi:

Makale

Yayın Tarihi:

1/2023

Belge Dili:

Türkçe

Document ID (Org No.):

2001281924

pISSN:

2792-0542