Investigation of D-e-MAPP-derived Cytotoxicity on Human Prostate Cancer Cells

Hüseyin İZGÖRDÜ, (Eskisehir Technical University)
Canan VEJSELOVA SEZER, (Eskisehir Technical University)
Emre ÇÖMLEKÇİ, (Eskisehir Technical University)
Hatice Mehtap KUTLU (Eskisehir Technical University)
Bilecik Şeyh Edebali Üniversitesi Fen Bilimleri Dergisi
3 0
Yıl: 2019 Cilt: 6 Sayı: 1a Sayfa Aralığı: 204 - 212 Metin Dili: İngilizce DOI: 10.35193/bseufbd.597942 İndeks Tarihi: 09-01-2020

Investigation of D-e-MAPP-derived Cytotoxicity on Human Prostate Cancer Cells

Öz:
Sphingolipids play critical role in biological processes such cell death, survival and drug resistancein many cancers. Ceramide and dihydroceramide are proliferation and death associated sphingolipids.Recent cancer research are focused on clarifying cancer-sphingolipid metabolism. In last years, ceramide asa key molecule in sphingolipid metabolism relationship has been investigated for its anticancer activity viaaugmenting its intracellular level by ceramidase inhibitor application. Prostate cancer is among the most frequenthuman cancers and is reported as second most common cancer-related death cause. Prostate cancer is common atages older than 65. The aim of this study was to investigate the potential cytotoxic activity of a ceramidase inhibitor(1S,2R)-D-erythro-2-(N-Myristoylamino)-1-phenyl-1-propanol (D-erythro-MAPP) on human prostate cancer DU-145cells by using MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay, flow cytometry, confocaland TEM microscopy. MTT findings showed that D-erythro-MAPP caused toxicity in low doses on DU-145 cells.Confocal and TEM microscopy findings indicated hole formation in cytoskeleton, chromatin condensation, horseshoeshaped cell nuclei as morphological changes and blebbings on cell membrane, fragmentation of nuclei, chromatincondensation and loss of cristae as ultrastructural changes, respectively. Flow cytometry findings showed that Derythro-MAPP triggered apoptosis in short-term application of 24 hours on DU-145 cells. According to results it canbe concluded that D-erythro-MAPP decreased viability of DU-145 cells in dose-dependent manner. Our findingsstated the anti-cancer and cytotoxic potential of D-erythro-MAPP on DU-145 and this agent might be used in drugdeveloping for cancer treatment after the further in vitro and in vivo studies.
Anahtar Kelime:

İnsan Prostat Kanseri Hücrelerinde D-e-MAPP kaynaklı Sitotoksisitenin Araştırılması

Öz:
- Sfingolipidler, birçok kanserde hücre ölümü, hayatta kalma ve ilaç direnci gibi biyolojik işlemlerde kritik rol oynamaktadır. Seramid ve dihidroseramid, proliferasyon ve ölüme bağlı olan sfingolipidlerdir. Son kanser araştırmaları, kanser-sfingolipid metabolizmasının netleştirilmesine odaklanmıştır. Son yıllarda, sfingolipid metabolizması ilişkisinde kilit bir molekül olarak seramid, antikanser aktivitesi için seramidaz inhibitör uygulaması ile hücre içi seviyesini arttırarak araştırılmıştır. Prostat kanseri, en sık görülen insan kanserleri arasındadır ve kansere bağlı en yaygın ikinci ölüm nedeni olarak rapor edilmektedir. Prostat kanseri, 65 yaşından büyüklerde yaygındır. Bu çalışmanın amacı, bir seramidaz inhibitörü olan (1S,2R)-D-erythro-2-(N-Myristoylamino)- 1-phenyl-1-propanol’un (D-eritro-MAPP) insan prostat kanseri DU-145 hücreleri üzerindeki potansiyel sitotoksik aktivitesini MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) testi, akış sitometrisi, konfokal ve TEM mikroskopisi kullanarak araştırmaktır. MTT bulguları D-eritro-MAPP'nin DU-145 hücrelerinde düşük dozlarda toksisiteye neden olduğunu göstermiştir. Konfokal ve TEM mikroskopi bulguları, hücre iskeletinde delik oluşumunu, kromatin yoğunlaşmasını, morfolojik değişiklikler olarak at nalı şeklindeki hücre çekirdeklerini ve hücre zarı üzerindeki tomurcuklanmaları, çekirdeklerin parçalanmasını, kromatin yoğunlaşmasını ve ultra yapısal değişiklikler olarak krista kaybını göstermiştir. Akış sitometrisi bulguları, D-eritro-MAPP'in DU-145 hücrelerine 24 saatlik kısa süreli uygulamasında apoptozu tetiklediğini göstermiştir. Elde edilen sonuçlara göre, D-eritro-MAPP'in DU-145 hücrelerinin canlılığını doza bağlı bir şekilde azalttığı söylenebilir. Bulgularımız, D-eritro-MAPP'in DU-145 hücreleri üzerindeki anti-kanser ve sitotoksik potansiyelini ortaya koymuştur ve bu ajanın, in vitro ve in vivo çalışmalardan sonra kanser tedavisi için ilaç geliştirmede kullanılabileceği belirtilmiştir.
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
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APA İZGÖRDÜ D, VEJSELOVA SEZER C, Çömlekçi E, KUTLU H (2019). Investigation of D-e-MAPP-derived Cytotoxicity on Human Prostate Cancer Cells. , 204 - 212. 10.35193/bseufbd.597942
Chicago İZGÖRDÜ Dr. Hüseyin,VEJSELOVA SEZER Canan,Çömlekçi Emre,KUTLU HATİCE MEHTAP Investigation of D-e-MAPP-derived Cytotoxicity on Human Prostate Cancer Cells. (2019): 204 - 212. 10.35193/bseufbd.597942
MLA İZGÖRDÜ Dr. Hüseyin,VEJSELOVA SEZER Canan,Çömlekçi Emre,KUTLU HATİCE MEHTAP Investigation of D-e-MAPP-derived Cytotoxicity on Human Prostate Cancer Cells. , 2019, ss.204 - 212. 10.35193/bseufbd.597942
AMA İZGÖRDÜ D,VEJSELOVA SEZER C,Çömlekçi E,KUTLU H Investigation of D-e-MAPP-derived Cytotoxicity on Human Prostate Cancer Cells. . 2019; 204 - 212. 10.35193/bseufbd.597942
Vancouver İZGÖRDÜ D,VEJSELOVA SEZER C,Çömlekçi E,KUTLU H Investigation of D-e-MAPP-derived Cytotoxicity on Human Prostate Cancer Cells. . 2019; 204 - 212. 10.35193/bseufbd.597942
IEEE İZGÖRDÜ D,VEJSELOVA SEZER C,Çömlekçi E,KUTLU H "Investigation of D-e-MAPP-derived Cytotoxicity on Human Prostate Cancer Cells." , ss.204 - 212, 2019. 10.35193/bseufbd.597942
ISNAD İZGÖRDÜ, Dr. Hüseyin vd. "Investigation of D-e-MAPP-derived Cytotoxicity on Human Prostate Cancer Cells". (2019), 204-212. https://doi.org/10.35193/bseufbd.597942
APA İZGÖRDÜ D, VEJSELOVA SEZER C, Çömlekçi E, KUTLU H (2019). Investigation of D-e-MAPP-derived Cytotoxicity on Human Prostate Cancer Cells. Bilecik Şeyh Edebali Üniversitesi Fen Bilimleri Dergisi, 6(1a), 204 - 212. 10.35193/bseufbd.597942
Chicago İZGÖRDÜ Dr. Hüseyin,VEJSELOVA SEZER Canan,Çömlekçi Emre,KUTLU HATİCE MEHTAP Investigation of D-e-MAPP-derived Cytotoxicity on Human Prostate Cancer Cells. Bilecik Şeyh Edebali Üniversitesi Fen Bilimleri Dergisi 6, no.1a (2019): 204 - 212. 10.35193/bseufbd.597942
MLA İZGÖRDÜ Dr. Hüseyin,VEJSELOVA SEZER Canan,Çömlekçi Emre,KUTLU HATİCE MEHTAP Investigation of D-e-MAPP-derived Cytotoxicity on Human Prostate Cancer Cells. Bilecik Şeyh Edebali Üniversitesi Fen Bilimleri Dergisi, vol.6, no.1a, 2019, ss.204 - 212. 10.35193/bseufbd.597942
AMA İZGÖRDÜ D,VEJSELOVA SEZER C,Çömlekçi E,KUTLU H Investigation of D-e-MAPP-derived Cytotoxicity on Human Prostate Cancer Cells. Bilecik Şeyh Edebali Üniversitesi Fen Bilimleri Dergisi. 2019; 6(1a): 204 - 212. 10.35193/bseufbd.597942
Vancouver İZGÖRDÜ D,VEJSELOVA SEZER C,Çömlekçi E,KUTLU H Investigation of D-e-MAPP-derived Cytotoxicity on Human Prostate Cancer Cells. Bilecik Şeyh Edebali Üniversitesi Fen Bilimleri Dergisi. 2019; 6(1a): 204 - 212. 10.35193/bseufbd.597942
IEEE İZGÖRDÜ D,VEJSELOVA SEZER C,Çömlekçi E,KUTLU H "Investigation of D-e-MAPP-derived Cytotoxicity on Human Prostate Cancer Cells." Bilecik Şeyh Edebali Üniversitesi Fen Bilimleri Dergisi, 6, ss.204 - 212, 2019. 10.35193/bseufbd.597942
ISNAD İZGÖRDÜ, Dr. Hüseyin vd. "Investigation of D-e-MAPP-derived Cytotoxicity on Human Prostate Cancer Cells". Bilecik Şeyh Edebali Üniversitesi Fen Bilimleri Dergisi 6/1a (2019), 204-212. https://doi.org/10.35193/bseufbd.597942
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23-04-2024 9:45

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