İnsan yumurtalık kanseri hücrelerinde NOE’nin apoptotik etkilerinin araştırılması

Yıl 2021, Cilt: 14 Sayı: 1, 132 - 137, 15.04.2021

Mustafa Albayrak Hatice Mehtap Kutlu

https://doi.org/10.46309/biodicon.2021.898960

Öz

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.

Anahtar Kelimeler

NOE, OVCAR-3, sitotoksisite

Investigation of apoptotic activities of NOE on human ovarian cancer cells

Öz

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.

Anahtar Kelimeler

NOE, OVCAR-3, cytotoxicity

Kaynakça

• Gault, C. R., Obeid, L. M. & Hannun, Y. A. (2010). An overview of sphingolipid metabolism: from synthesis to breakdown. Advances in Experimental Medicine and Biology, 688, 1-23.
• Mashhadi Akbar Boojar, M., Mashhadi Akbar Boojar, M. & Golmohammad, S. (2018). Ceramide pathway: A novel approach to cancer chemotherapy. Egyptian Journal of Basic and Applied Sciences, 5, 237–244.
• Ogretmen, B. & Hannun, Y. A. (2004). Biologically active sphingolipids in cancer pathogenesis and treatment. Nature Reviews Cancer, 4(8), 604-616.
• Sugita, M., Williams, M., Dulaney, J. T. & Moser, H. W. (1975). Ceramidase and ceramide synthesis in human kidney and cerebellum. Biochimicu et Biophysics Acta, 398, 125-131.
• López-Rodríguez, M., Viso, A., Ortega-Gutiérrez, S., Díaz-Laviada, I., López-Rodríguez, M. L., Viso, A. & Díaz-Laviada, I. (2005). Involvement of cannabinoids in cellular proliferation. Mini-Reviews in Medicinal Chemistry, 5(1), 97-106.
• Liu, X., Cheng, J. C., Turner, L. S., Elojeimy, S., Beckham, T. H., Bielawska, A. & Norris, J. S. (2009). Acid ceramidase upregulation in prostate cancer: role in tumor development and implications for therapy. Expert Opinion on Therapeutic Targets, 13(12), 1449-1458.
• Saied, E. M. & Arenz, C. (2016). Inhibitors of ceramidases. Chemistry and Physics of Lipids journal, 197, 60-68.
• Kitatani, K., Usui, T., Sriraman, S. K., Toyoshima, M., Ishibashi, M., Shigeta, S., Nagase, S., Sakamoto, M., Ogiso, H., Okazaki, T., Hannun, Y. A., Torchilin, V. P. & Yaegashi, N. (2016). Ceramide limits phosphatidylinositol-3-kinase C2β-controlled cell motility in ovarian cancer: potential of ceramide as a metastasis-suppressor lipid. Oncogene. 2801-2812. Lengyel, E. (2010). Ovarian cancer development and metastasis. Am. J. Pathol., 177,1053–1064.
• Banerjee, S. & Kaye, S. B. (2013). New strategies in the treatment of ovarian cancer: current clinical perspectives and future potential. Clin. Cancer. Res., 19, 961–968.
• Yamazaki, D., Kurisu,. S. & Takenawa, T. (2005). Regulation of cancer cell motility through actin reorganization. Cancer Sci., 96, 379–386.
• Çömlekçi, E., Kutlu, H. M. & Vejselova Sezer, C. (2020). A new agent for the treatment of lung cancer: B13 loaded solid lipid nanoparticles. Advances in Natural Sciences: Nanoscience and Nanotechnology, 11 (4), 11 045014.
• Vejselova Sezer, C. (2021). Cytotoxic impacts of escin via inducing apoptosis and morphological changes on human prostate cancer cells. Biological Diversity and Conservation, 14 (1), 82-87.
• Kitatani, K., Idkowiak-Baldys, J. & Hannun, Y. A. (2008). The sphingolipid salvage pathway in ceramide metabolism and signaling. Cell Signal., 20, 1010–1018.
• Ogretmen, B., Pettus, B. J., Rossi, M. J., Wood, R., Usta, J., Szulc, Z., Bielawska, A., Obeid, L. M. & Hannun, Y. A. (2002). Biochemical mechanisms of the generation of endogenous long chain ceramide in response to exogenous short chain ceramide in the A549 human lung adenocarcinoma cell line. Role for endogenous ceramide in mediating the action of exogenous ceramide. J. Biol. Chem., 277, 12960–12969.