Meme kanserinde B13-klorokin uygulamasıyla in vitro tedavi araştırması

Abstract

Kanser hastalığı hala halk sağlığı için ciddi bir tehdit olmaya devam edmektedir. Meme kanseri tedavisi için yeni tedavi yaklaşımlarına ve yan etkisi düşük ajanlara ihtiyaç duyulmaktadır. Bunlara dayanarak, burada bir seramidaz inhibitörü (B13) ve bir otofaji inhibitörü (klorokin) içeren bir kombinasyonun insan meme kanseri hücre hattı üzerindeki sitotoksisitesinin araştırılması amaçlanmıştır. Antiproliferatif aktivite, Sulforhodamine B ve ATP canlılık deneyleri ile test edilmiştir. MCF-7 hücrelerinin ince yapısal ve morfolojik değişiklikleri ve apoptotik belirtileri için TEM ve konfokal mikroskopi teknikleri kullanılmıştır. Sonuçlar, kombinasyonun yüksek sitotoksik ve antiproliferatif aktivitelerinin yanı sıra apoptozu gösteren ince yapısal ve morfolojik değişikliklere neden olduğunu göstermiştir. B13+Klorokin kombinasyonunun MCF-7 hücrelerinde ölümü tetiklediği, antiproliferatif ve sitotoksik etkilere neden olduğu saptanmıştır. Sonuç olarak, yeni kombinasyonun antikanser bir ajan olarak ileri araştırmalar için iyi bir aday olduğu ortaya konulmuştur.

Keywords

• MCF-7
• kombine terapi
• sitotoksisite
• B13
• klorokin

In vitro therapy investigation for breast cancer by B13-chloroquine application

Abstract

Cancer disease still remains to be strong treat for public health. New treatment approaches and agents with low side effects are needed for the treatment of breast cancer. Based on these, herein was aimed to investigate the cytotoxicity of a combination comprising a ceramidase inhibitor (B13) and an autophagy inhibitor (chloroquine) on human breast cancer cell line. The antiproliferative activity was tested by Sulforhodamine B and ATP viability assays. For ultrastructural and morphological changes and apoptotic signs of MCF-7 cells were used TEM and confocal microscopy techniques. Results showed the high cytotoxic and antiproliferative activities of the combination along with the ultrastructural and morphological changes indicating apoptosis. B13+Chloroquine combinations found to be effective on inducing cell death on MCF-7 cells and antiproliferative and cytotoxic effects on cells. Consequently, the new combination is suggested as good candidate for further investigations to be an anti-cancer agent.

Keywords

• MCF-7
• combination therapy
• cytotoxicity
• B13
• chloroquine

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