İnsan yumurtalık kanseri hücrelerinde NOE’nin apoptotik etkilerinin araştırılması

Abstract

Yumurtalık kanseri, kadınların üreme sistemindeki en kötü huylu kanserlerden biridir. Diğer kanser türleri ile birlikte yumurtalık kanseri, klasik kemoterapötiklerin sınırlı etkinliği ve güçlü yan etkileri ve uzun tedavi süreci nedeniyle tedavi için alternatif ajanlara ihtiyaç duymaktadır. Son zamanlarda, kanser araştırmaları, kanser tedavisi için hücre içi hedeflere odaklanmaktadır. Sfingolipid molekülleri, özellikle seramidler, kanser tedavisi için güçlü hedefler olarak gösterilmektedir. Seramidlerin kanser hücrelerinde artan miktarları, apoptozu indüklemektedir ve bu artış, seramidazların yeni nesil enzim inhibitörleri yoluyla baskılanmasından kaynaklanabilmektedir. Bu çalışmada, insan yumurtalık kanseri hücreleri OVCAR-3'te sitotoksisiteye yol açmak ve apoptozu indüklemek için bir seramidaz inhibitörü olan NOE (Oleoyl ethanolamide) kullanılmıştır. Sonuçlarımız, NOE'nin hücre canlılığını önemli ölçüde azalttığını ve akış sitometri sonuçları ile kanıtlanmış apoptozu gösteren morfolojik değişikliklerle birlikte sitotoksisiteye neden olduğunu açıkça göstermiştir. NOE, daha ileri araştırmalardan sonra anti-kanser ajanı tasarlanması için aday olarak tarafımızdan önerilmektedir.

Keywords

• NOE
• OVCAR-3
• sitotoksisite

Investigation of apoptotic activities of NOE on human ovarian cancer cells

Abstract

Ovarian cancer is one of the most malignan cancers of the reproductive system of womans. Along with the other cancer types, ovarian cancer requires alternative agents for treatment due to the limited efficiency and strong side effects of classical chemotherapeutics and long treatment process. Recently, cancer investigations are focused on intracellular targets for cancer therapy. Sphingolipid molecules, especially ceramides of them are reported as potent targets for cancer therapy. İncreased leves of ceramides into the cancer cells induce apoptosis and this increase can be caused by supressing ceramidases via new generation inhibitors of the enzymes. In this study, NOE (Oleoyl ethanolamide), a ceramidase inhibitor was used to cause cytotoxicity and induce apoptosis in human ovarian cancer cells, OVCAR-3. Our results clearly showed that NOE significantly reduced cell viability and caused cytotoxicity together with morphological changes indicating apoptosis that is proved with the flow cytometry results. NOE is proposed for a candicate for designing anti-cancer agent after further investigations.

Keywords

• NOE
• OVCAR-3
• cytotoxicity

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