PhTAD-Substituted Dihydropyrrole Compounds Regulate Apoptotic Cell Death in MCF-7 Cells

Year 2021, , 737 - 750, 31.08.2021

Burak Yazgan , Seda Mesci , Masuk Aksahın , Arif Ayar , Melek Gül , Tuba Yıldırım

https://doi.org/10.18185/erzifbed.894125

Abstract

Breast cancer is the most common type of cancer amongst women. Apoptosis is known as a programmed cell death and this mechanism induces cancer cell death. Dihydropyrrole compounds contain a heterocyclic structure and these molecules have many biological effects including functioning as antioxidants and anticancer molecules.
In this regard, the aim of this research was to investigate how PhTAD-substituted dihydropyrrole compounds affect the expression of apoptotic cell death proteins in the MCF-7 cells. The levels of Bax, Bcl-2, and cleaved caspase-3 proteins in the MCF-7 cells were measured using the ELISA method.
The results revealed that CI, CII, CIII, CV, CVII, CVIII, CXI and CXII increased Bax, while CXIII and CXIV markedly decreased Bax. In addition, compounds CI, CII, CIII, CVII, CVIII, CXI and CXII upregulated Bcl2. Conversely, CIV, and CXIV downregulated Bcl2. Moreover, CIV and CXIV increased the Bax/Bcl2 ratio. However, CVIII and CXIII decreased Bax/Bcl2 ratio. In addition, CI, CIV, CIX and CXII treatment increased cleaved caspase-3 in MCF-7 cells compared to the negative control. These findings indicate that the PhTAD-substituted dihydropyrrole derivative molecules induced apoptotic proteins as a potential regulator of cancer cell death.

Keywords

Breast Cancer, PhTAD-Dihydropyrrole, Apoptosis, BCL2 family, Caspase 3

Supporting Institution

Amasya University

Project Number

FMB-BAP 18-0334

Thanks

The authors thank the Amasya University Central Research Laboratory (AUMAULAB) for their kind understanding of using their facilities.

PhTAD-Sübstitüe Dihidropirol Bileşikleri MCF-7 Hücrelerinde Apoptotik Hücre Ölümünü Düzenler

Abstract

Meme kanseri, kadınlar arasında en sık görülen kanser türüdür. Apoptoz, programlanmış hücre ölümü olarak bilinir ve bu mekanizma kanser hücrelerinin ölümünü indükler. Dihidropirol bileşikleri heterosiklik bir yapı içerir ve bu moleküllerin antioksidan ve antikanser gibi birçok biyolojik etkisi vardır.
Bu noktada, Çalışmamızın amacı, PhTAD türevli dihidropirol bileşiklerinin MCF-7 hücrelerindeki apoptotik hücre ölüm proteinlerinin ifadesini nasıl etkilediğini araştırmaktır.
Bax, Bcl-2 ve kesilmiş kaspaz 3'ün protein miktarları, MCF-7 hücre hattında ELISA yöntemi ile ölçülmüştür.
Sonuçlarımız, bileşik (B)I, BII, BIII, BV, BVII, BVIII, BXI ve BXII'nin Bax'ı artırdığını, BXIII ve BXIV'ün ise Bax'ı önemli ölçüde azalttığını ortaya koymuştur. Ek olarak, BI, BII, BIII, BVII, BVIII, BXI ve BXII’nin Bcl2'yi yukarı regüle ederken BIV, BXIII ve BXIV’ün Bcl2'yi aşağı regüle ettiği tespit edilmiştir. Ayrıca, BIV ve BXIV’ün Bax / Bcl2 oranını arttırdığı, BVIII ve BXIII’ün ise Bax / Bcl2 oranını düşürdüğü belirlenmiştir. Negatif kontrole kıyasla BI, BIV, BIX ve BXII uygulanan MCF-7 hücrelerinde kesilmiş kaspaz 3 ekspresyonunun arttığı tespit edilmiştir.
Bulgularımız, PhTAD ile türevlendirilmiş dihidropirol moleküllerinin, kanser hücresi ölümünün potansiyel bir düzenleyicisi olarak apoptotik proteinleri indüklediğine işaret etmektedir.

Keywords

Meme Kanseri, PhTAD-dihidropirol, Apoptoz, Bcl2 ailesi, Kaspaz 3

Project Number

FMB-BAP 18-0334

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