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

Year 2020, , 356 - 366, 21.06.2020

Yavuz Erden , Sevilay Günay

https://doi.org/10.33715/inonusaglik.723439

Cited By: 2

Abstract

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.

Keywords

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

Supporting Institution

Bartın Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi

Project Number

2019-FEN-A-003

Thanks

Bu çalışma Bartın Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi tarafından desteklenmiştir (Proje No: 2019-FEN-A-003).

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

Abstract

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

Project Number

2019-FEN-A-003

References

• Ali R, Rani R, Kumar S. New peptide based therapeutic approaches, Advances in Protein Chemistry. Jeddah: OMICS Group eBooks, 2013.
• Blanco-Miguez A, Gutierrez-Jacome A, Perez-Perez M, Perez-Rodriguez G, Catalan-Garcia S, Fdez-Riverola F, Lourenco A, Sanchez B. From amino acid sequence to bioactivity: The biomedical potential of antitumor peptides, Protein Sci, 2016; 25(6): 1084-1095.
• Boohaker RJ, Lee MW, Vishnubhotla P, Perez JM, Khaled AR. The use of therapeutic peptides to target and to kill cancer cells, Curr Med Chem, 2012; 19(22): 3794-3804.
• Cicero AFG, Fogacci F, Colletti A. Potential role of bioactive peptides in prevention and treatment of chronic diseases: a narrative review, Br J Pharmacol, 2017; 174(11): 1378-1394.
• Domingo-Calap P, Delgado-Martínez J. Bacteriophages: protagonists of a post-antibiotic era, Antibiotics, 2018; 7(3): 66.
• Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation, Cell, 2011; 144(5): 646-674.
• Hayashi M, Ducancel F, Konno K. Natural Peptides with Potential Applications in Drug Development, Diagnosis, and/or Biotechnology, Int J Pept, 2012a; 2012: 757838.
• Hayashi MA, Ducancel F, Konno K. Natural peptides with potential applications in drug development, diagnosis, and/or biotechnology, International journal of peptides, 2012b; 2012.
• Hilchie AL, Sharon AJ, Haney EF, Hoskin DW, Bally MB, Franco OL, Corcoran JA, Hancock RE. Mastoparan is a membranolytic anti-cancer peptide that works synergistically with gemcitabine in a mouse model of mammary carcinoma, Biochimica Et Biophysica Acta (BBA)-Biomembranes, 2016; 1858(12): 3195-3204.
• Jackson AL, Loeb LA. The contribution of endogenous sources of DNA damage to the multiple mutations in cancer, Mutat Res, 2001; 477(1-2): 7-21.
• Jang M, Kim SS, Lee J. Cancer cell metabolism: implications for therapeutic targets, Exp Mol Med, 2013; 45: e45.
• Koran K, Tekin Ç, Çalışkan E, Tekin S, Sandal S, Görgülü AO. Synthesis, structural and thermal characterizations and in vitro cytotoxic activities of new cyclotriphosphazene derivatives, Phosphorus, Sulfur, and Silicon and the Related Elements, 2017; 192(9): 1002-1011.
• Li F-M, Wang X-Q. Identifying anticancer peptides by using improved hybrid compositions, Scientific reports, 2016; 6: 33910.
• Marqus S, Pirogova E, Piva TJ. Evaluation of the use of therapeutic peptides for cancer treatment, Journal of biomedical science, 2017a; 24(1): 21.
• Marqus S, Pirogova E, Piva TJ. Evaluation of the use of therapeutic peptides for cancer treatment, J Biomed Sci, 2017b; 24(1): 21.
• McGregor DP. Discovering and improving novel peptide therapeutics, Curr Opin Pharmacol, 2008; 8(5): 616-619.
• Meisel C, Bonhagen K, Lohning M, Coyle AJ, Gutierrez-Ramos JC, Radbruch A, Kamradt T. Regulation and function of T1/ST2 expression on CD4+ T cells: induction of type 2 cytokine production by T1/ST2 cross-linking, J Immunol, 2001; 166(5): 3143-3150.
• Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays, J Immunol Methods, 1983; 65(1-2): 55-63.
• Ohana J, Sandler U, Kass G, Stemmer SM, Devary Y. dTCApFs, a derivative of a novel human hormone peptide, induces apoptosis in cancer cells through a mechanism involving loss of Golgi function, Mol Clin Oncol, 2017; 7(6): 991-999.
• Sandler U, Devary O, Braitbard O, Ohana J, Kass G, Rubinstein AM, Friedman ZY, Devary Y. NEROFE--a novel human hormone-peptide with anti-cancer activity, J Exp Ther Oncol, 2010; 8(4): 327-339.
• Singh NP, McCoy MT, Tice RR, Schneider EL. A simple technique for quantitation of low levels of DNA damage in individual cells, Exp Cell Res, 1988; 175(1): 184-191.
• Stemmer SM, Benjaminov O, Silverman MH, Sandler U, Purim O, Sender N, Meir C, Oren-Apoteker P, Ohana J, Devary Y. A phase I clinical trial of dTCApFs, a derivative of a novel human hormone peptide, for the treatment of advanced/metastatic solid tumors, Mol Clin Oncol, 2018; 8(1): 22-29.
• Tekin S, Erden Y, Sandal S, Yilmaz B. Is irisin an anticarcinogenic peptide?, Med-Science, 2015; 4(2): 2172-2180.
• Tominaga S. A putative protein of a growth specific cDNA from BALB/c-3T3 cells is highly similar to the extracellular portion of mouse interleukin 1 receptor, FEBS Lett, 1989; 258(2): 301-304.
• Tyagi A, Kapoor P, Kumar R, Chaudhary K, Gautam A, Raghava G. In silico models for designing and discovering novel anticancer peptides, Scientific reports, 2013; 3: 2984.
• Wagner PD, Srivastava S. New paradigms in translational science research in cancer biomarkers, Transl Res, 2012; 159(4): 343-353.
• Wang X, Kaczor-Urbanowicz KE, Wong DT. Salivary biomarkers in cancer detection, Med Oncol, 2017; 34(1): 7.
• Xu D, Chan WL, Leung BP, Huang F, Wheeler R, Piedrafita D, Robinson JH, Liew FY. Selective expression of a stable cell surface molecule on type 2 but not type 1 helper T cells, J Exp Med, 1998; 187(5): 787-794.