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TÜMÖR HÜCRELERİ APOPTOZ FAKTÖRÜ (TCApF)’NÜN İNSAN PROSTAT VE MEME KANSERİ HÜCRE HATLARI ÜZERİNE SİTOTOKSİK VE GENOTOKSİK ETKİLERİNİN BELİRLENMESİ

Antikanser peptidler (ACP), moleküler hedefli kanser ilaç keşif ve gelişim süreci için önemli bir strateji olarak görülmektedir. ACP’ler kullanılarak normal hücrelere toksik etkileri azaltılmış yeni terapötik ilaçların tasarlanabileceği öngörülmektedir. Tümör hücreleri apoptoz faktörü (TCApF), 84 aminoasit uzunluğunda peptid yapısına sahip yeni bir hormondur. Bu hormon üzerine yapılan az sayıdaki araştırma TCApF’nin potansiyel bir ACP olabileceğini bildirmektedir. Bu çalışmanın amacı, insan meme (MCF-7) ve prostat kanseri (PC-3) hücre hatları üzerine TCApF’nin muhtemel sitotoksik ve genotoksik etkilerini belirlemektir. Çalışmada insan meme ve prostat kanser hücre hatları üzerine TCApF’nin 1, 10 ve 100 ve 1000 ng/ml’lik konsantrasyonları ile referans ilaç (5-Fluorourasil) 24 ve 48 saat süreyle uygulandı. Uygulamayı takiben TCApF’nin hücre canlılıkları üzerine etkileri MTT yöntemiyle, DNA hasarına etkisi ise tek hücre jel elektroforezi yöntemi (Comet Assay) ile belirlendi. Sonuç olarak uygulanan 1000 ng/ml’lik dozun her iki hücre hattında da hücre canlılığını azalttığını ve düşük seviyede DNA hasarına neden olduğunu tespit ettik. Bu sonuçlar TCApF’nin potansiyel bir ACP olabileceğini ancak düşük dozlarda etki sergilemediğini göstermektedir.

Anahtar Kelimeler:

Antikanser peptid, Genotoksisite, Meme kanseri, Prostat kanseri, Sitotoksisite, TCApF

Determination of Cytotoxic and Genotoxic Effects of Tumor Cells Apoptosis Factor (TCApF) on Human Prostate and Breast Cancer Cell Lines

Anticancer peptides (ACP) are thought as an important strategy for molecular targeted cancer drug discovery and development process. It is predicted that new therapeutic drugs with reduced toxic effects to normal cells can be designed by using ACPs. Tumor cells apoptosis factor (TCApF) is a new peptide structured hormone with a length of 84 amino acids. Few studies on this hormone report that TCApF may be a potential ACP. The aim of this study is to determine the possible cytotoxic and genotoxic effects of TCApF on human breast (MCF-7) and prostate cancer (PC-3) cell lines. In the present study, concentrations of 1, 10 and 100 and 1000 ng/ml of TCApF, as well as a reference drug (5- fluorouracil), were applied on human breast and prostate cancer cell lines for 24 and 48 hours. Following the application, the effects of TCApF on cell viability were determined by MTT method, and the effect on DNA damage was determined by single cell gel electrophoresis method (Comet Assay). As the result, we determined that the applied dose of 1000 ng/ml reduces cell viability in both cell lines and causes low level of DNA damage. These results show that TCApF may be a potential ACP, but it does not exhibit effect at low doses.

Keywords:

Anticancer peptide, Breast cancer, Genotoxicity, Prostate cancer, TCApF,

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