Investigation of the cytotoxic/genotoxic potential of the combination of tamoxifen and fluoxetine applied to SKOV3 cells

Öz

Aim: Breast cancer is the most common malignancy in women, and tamoxifen has been used as an effective therapeutic agent for many years in estrogen receptor-positive cases. Fluoxetine is an antidepressant used in the treatment and management of depression and psychiatric disorders. People can be exposed to these drugs through various routes, primarily through medical use. This exposure can affect the genome. Multiple exposures of living organisms to chemicals may result in more severe consequences than single administrations. Therefore, the present study aimed to determine the cytotoxic and genotoxic potential of the combined use of tamoxifen and fluoxetine on ovarian cancer cells. Methods: Tamoxifen doses of 5, 10, 20, 40, and 60 μM and fluoxetine doses of 1, 5, 10, 15, and 20 μM were first administered individually to SKOV3 cells. Subsequently, SKOV3 cells were exposed to the drug combination. Cytotoxicity assessment after exposure was performed using the xCELLigence real-time cell analysis system, and genotoxicity assessment was performed using the alkaline comet assay. Results: Data obtained with the xCELLigence analysis showed that treatment with the drug combination resulted in higher cytotoxicity than single drug applications. Comet analysis showed that drug combinations increased the percentage of damaged cells and the genetic damage index almost twofold compared to single drug exposure. Conclusion: It has been determined that drug combinations can exhibit synergistic effects compared to single applications, leading to more severe toxic effects on human health. These findings necessitate evaluating the potential toxicity of various drug combinations and the synergistic effects of varying concentrations in different ecosystems, particularly wastewater.

Anahtar Kelimeler

• Fluoxetine
• genotoxicity
• cytotoxicity
• tamoxifen
• cancer

Proje Numarası

BAP 2019-1-TP2-3337

SKOV3 hücrelerine uygulanan tamoksifen ve floksetin kombinasyonunun sitotoksik/genotoksik potansiyelinin araştırılması

Öz

Amaç: Meme kanseri, kadınlarda en sık görülen malignite türü olup, bu hastalığın tedavisinde östrojen reseptör pozitif vakalar için tamoksifen uzun yıllardır etkili bir terapötik ajan olarak kullanılmaktadır. Floksetin ise depresyon ve psikiyatrik bozuklukların tedavisi ve kontrolünde kullanılan bir antidepresandır. İnsanlar bu ilaçlara medikal uygulamalar başta olmak üzere farklı yollarla maruz kalabilmektedirler. Bu maruziyet genomu etkileyebilmektedir. Canlıların kimyasallara çoklu maruziyeti tekli uygulamalardan daha riskli sonuçlar doğurabilir. Bu nedenle, sunulan bu çalışmada tamoksifen ve floksetinin beraber kullanımının ovaryum kanser hücreleri üzerindeki sitotoksisite ve genotoksisite potansiyelinin belirlenmesi amaçlanmıştır. Yöntem: Tamoksifenin 5, 10, 20, 40 ve 60 μM’lık dozları ve floksetinin 1, 5, 10, 15 ve 20 μM’lık dozları önce tekli olarak SKOV3 hücrelerine uygulanmıştır. Daha sonra, SKOV3 hücreleri kombinasyon halinde ilaçlara maruz bırakılmıştır. Maruziyetler sonrasında sitotoksisite değerlendirmesi xCELLigence gerçek zamanlı hücre analiz sistemi kullanılarak, genotoksisite değerlendirmesi ise alkalin komet testi kullanılarak gerçekleştirilmiştir. Bulgular: xCELLigence analiziyle elde edilen veriler, kombinasyon şeklindeki uygulamanın tekli ilaç uygulamalarından daha yüksek sitotoksisiteye neden olduğunu göstermiştir. Komet analizi sonucunda ise ilaç kombinasyonlarının hasarlı hücre yüzdesini ve genetik hasar indeksini tekli ilaç maruziyetine oranla neredeyse iki kat arttırdığı gözlemlenmiştir. Sonuç: İlaç kombinasyonlarının tekli uygulamalara kıyasla sinerjistik etki göstererek insan sağlığı üzerinde daha ciddi toksik etkilere yol açabileceği belirlenmiştir. Bu bulgular, farklı ilaç kombinasyonlarının potansiyel toksisitelerinin özellikle atık sular başta olmak üzere farklı ekosistemlerdeki, farklı konsantrasyonların sinerjistik etkilerinin değerlendirilmesini zorunlu kılmaktadır.

Anahtar Kelimeler

• Floksetin
• genotoksisite
• sitotoksisite
• tamoksifen
• kanser

Destekleyen Kurum

Mersin Üniversitesi

Proje Numarası

BAP 2019-1-TP2-3337

Teşekkür

Çalışmanın gerçekleşmesine mali destek sağlayan Mersin Üniversitesi Bilimsel Araştırmalar Projeleri Birimine teşekkür ederiz.

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