Effect of Flavopiridol on Cell Cycle, Apoptosis and Biomolecule Structure Changes in Breast Cancer Stem Cells
Yıl: 2020 Cilt: 8 Sayı: 3 Sayfa Aralığı: 275 - 281 Metin Dili: İngilizce DOI: 10.14235/bas.galenos.2019.3491 İndeks Tarihi: 14-11-2020
Effect of Flavopiridol on Cell Cycle, Apoptosis and Biomolecule Structure Changes in Breast Cancer Stem Cells
Öz: Objective: Cancer stem cells (CSCs) are a small population incancer, which are responsible for therapeutic resistance, relapse andmetastasis. Flavopiridol has antitumor activity against various typesof cancer cells. The mechanism of action of flavopiridol on CD44+/CD24- breast CSCs has not yet been fully elucidated. The aim ofthis study was to evaluate the mechanism of action of flavopiridolon breast CSCs (BCSC) in terms of apoptosis, cell cycle andbiomolecular changes.Methods: In human breast cancer, cells with CD44+/CD24−markers were isolated from MCF-7 cell line using flow cytometry.The induction of apoptosis was investigated by Annexin-V. Theeffect of flavopiridol on cell cycle arrest was determined and thepercent of cell populations at G0/G1, S and G2/M cycles wereidentified. The effect of the drug on three-dimensional cell cultureswas investigated using a multicellular tumor spheroid model.In addition, the effect of flavopiridol on biomolecules has beenevaluated using Fourier transform infrared (FTIR) spectroscopy,which has recently been used effectively in various scientific fields.Results: Flavopiridol especially induced early apoptosis. Cell cycleanalyses revealed that flavopiridol induced cell cycle arrest in G0/G1phase. Decreased number and diameter of spheroids was observedfollowing flavopiridol treatment. ATR-FTIR data showed thattreatment with flavopiridol led to significant changes in nucleicacids.Conclusion: According to the data obtained in this study,flavopiridol exhibits anticancer effects by altering the structure/expression level of nucleic acids and changing cell cycle progressionand inducing apoptosis. These finding reveals that flavopiridol canbe an effective antitumor agent for the treatment of breast cancerafter in vivo and phase studies are completed.
Anahtar Kelime: Meme Kanseri Kök Hücrelerinde Flavopiridolün Hücre Döngüsü, Apoptozis ve Biyomolekül Yapı Değişimleri Üzerine Etkisi
Öz: Amaç: Kanser kök hücreleri (KKH) terapötik direnç, relaps ve metastazdan sorumlu olan oldukça küçük bir hücre popülasyondan oluşmaktadır. Flavopiridol (Alvocidib), çeşitli KKH’lerine karşı anti-tümör aktiviteye sahiptir. Flavopiridolün CD44+/CD24- meme KKH (MKKH) üzerindeki etki mekanizması henüz tam olarak aydınlatılamamıştır. Bu çalışmada, apoptozis, hücre döngüsü ve biyomoleküler değişiklikler dahil olmak üzere flavopiridolün MKKH üzerindeki etki mekanizmasının çeşitli şekillerde değerlendirilmesi amaçlanmıştır. Yöntemler: MCF-7 KKH hattı içerisindeki CD44+/CD24- yüzey belirteç özelliklerine sahip MKKH, akış sitometrisi kullanılarak izole edilmiştir. Apoptozis indüksiyonu Annexin-V yöntemi ile incelenmiştir. Flavopiridolün hücre döngüsü tutulumu üzerine etkisi Muse Cell Analyzer ile belirlenmiş ve G0/G1, S ve G2/M döngüsündeki hücre populasyonları yüzde olarak ifade edilmiştir. İlacın üç boyutlu hücre kültürlerindeki etkisi multiselüler tümör sferoid modeli kullanılarak incelenmiştir. Buna ek olarak, flavopiridolün biyomoleküller üzerindeki etkisi, son zamanlarda çeşitli alanlarda oldukça etkin bir şekilde kullanılan Fourier dönüşüm kızılötesi (FTIR) spektroskopisi kullanılarak değerlendirilmiştir. Bulgular: Flavopiridol spesifik olarak erken apoptozu indüklemiştir. Hücre döngü analizleri, flavopiridolün G0/G1 arrestine yol açtığını ortaya koymuştur. Flavopiridol uygulamasından sonra sferoid sayısı ve çapında azalma tespit edilmiştir. ATR-FTIR verileri, flavopiridol uygulamasının hücre içindeki nükleik asitlerde önemli değişimlere yol açtığını göstermiştir. Sonuç: Elde edilen bulgular, flavopiridolün nükleik asitlerin yapısını/expresyon seviyesini ve hücre döngüsünü değiştirdiğini ve apoptozu indükleyerek anti-kanser etkiler sergilediğini göstermektedir. Bu veriler, in vivo ve faz çalışmaları tamamlandıktan sonra flavopiridolün meme kanser tedavisi için etkili bir terapötik molekül olabileceğini ortaya koymaktadır.
Anahtar Kelime: Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
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| APA | Acikgoz E, Güler G, Öktem G (2020). Effect of Flavopiridol on Cell Cycle, Apoptosis and Biomolecule Structure Changes in Breast Cancer Stem Cells. , 275 - 281. 10.14235/bas.galenos.2019.3491 |
| Chicago | Acikgoz Eda,Güler Günnur,Öktem Gülperi Effect of Flavopiridol on Cell Cycle, Apoptosis and Biomolecule Structure Changes in Breast Cancer Stem Cells. (2020): 275 - 281. 10.14235/bas.galenos.2019.3491 |
| MLA | Acikgoz Eda,Güler Günnur,Öktem Gülperi Effect of Flavopiridol on Cell Cycle, Apoptosis and Biomolecule Structure Changes in Breast Cancer Stem Cells. , 2020, ss.275 - 281. 10.14235/bas.galenos.2019.3491 |
| AMA | Acikgoz E,Güler G,Öktem G Effect of Flavopiridol on Cell Cycle, Apoptosis and Biomolecule Structure Changes in Breast Cancer Stem Cells. . 2020; 275 - 281. 10.14235/bas.galenos.2019.3491 |
| Vancouver | Acikgoz E,Güler G,Öktem G Effect of Flavopiridol on Cell Cycle, Apoptosis and Biomolecule Structure Changes in Breast Cancer Stem Cells. . 2020; 275 - 281. 10.14235/bas.galenos.2019.3491 |
| IEEE | Acikgoz E,Güler G,Öktem G "Effect of Flavopiridol on Cell Cycle, Apoptosis and Biomolecule Structure Changes in Breast Cancer Stem Cells." , ss.275 - 281, 2020. 10.14235/bas.galenos.2019.3491 |
| ISNAD | Acikgoz, Eda vd. "Effect of Flavopiridol on Cell Cycle, Apoptosis and Biomolecule Structure Changes in Breast Cancer Stem Cells". (2020), 275-281. https://doi.org/10.14235/bas.galenos.2019.3491 |
| APA | Acikgoz E, Güler G, Öktem G (2020). Effect of Flavopiridol on Cell Cycle, Apoptosis and Biomolecule Structure Changes in Breast Cancer Stem Cells. Bezmiâlem Science, 8(3), 275 - 281. 10.14235/bas.galenos.2019.3491 |
| Chicago | Acikgoz Eda,Güler Günnur,Öktem Gülperi Effect of Flavopiridol on Cell Cycle, Apoptosis and Biomolecule Structure Changes in Breast Cancer Stem Cells. Bezmiâlem Science 8, no.3 (2020): 275 - 281. 10.14235/bas.galenos.2019.3491 |
| MLA | Acikgoz Eda,Güler Günnur,Öktem Gülperi Effect of Flavopiridol on Cell Cycle, Apoptosis and Biomolecule Structure Changes in Breast Cancer Stem Cells. Bezmiâlem Science, vol.8, no.3, 2020, ss.275 - 281. 10.14235/bas.galenos.2019.3491 |
| AMA | Acikgoz E,Güler G,Öktem G Effect of Flavopiridol on Cell Cycle, Apoptosis and Biomolecule Structure Changes in Breast Cancer Stem Cells. Bezmiâlem Science. 2020; 8(3): 275 - 281. 10.14235/bas.galenos.2019.3491 |
| Vancouver | Acikgoz E,Güler G,Öktem G Effect of Flavopiridol on Cell Cycle, Apoptosis and Biomolecule Structure Changes in Breast Cancer Stem Cells. Bezmiâlem Science. 2020; 8(3): 275 - 281. 10.14235/bas.galenos.2019.3491 |
| IEEE | Acikgoz E,Güler G,Öktem G "Effect of Flavopiridol on Cell Cycle, Apoptosis and Biomolecule Structure Changes in Breast Cancer Stem Cells." Bezmiâlem Science, 8, ss.275 - 281, 2020. 10.14235/bas.galenos.2019.3491 |
| ISNAD | Acikgoz, Eda vd. "Effect of Flavopiridol on Cell Cycle, Apoptosis and Biomolecule Structure Changes in Breast Cancer Stem Cells". Bezmiâlem Science 8/3 (2020), 275-281. https://doi.org/10.14235/bas.galenos.2019.3491 |
