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. 2019 Feb;120(2):1282-1293.
doi: 10.1002/jcb.27089. Epub 2018 Oct 28.

Investigation of the effect of telomerase inhibitor BIBR1532 on breast cancer and breast cancer stem cells

Fatma Doğan  1 , Neslihan Pınar Özateş  1 , Bakiye Göker Bağca  1 , Zeka Abbaszadeh  1 , Fatma Söğütlü  1 , Röya Gasımlı  1 , Cumhur Gündüz  1 , Çığır Biray Avcı  1
Affiliations

Investigation of the effect of telomerase inhibitor BIBR1532 on breast cancer and breast cancer stem cells

Fatma Doğan et al. J Cell Biochem. 2019 Feb.

Abstract

It is emphasized that cancer stem cells (CSCs) forming the subpopulation of tumour cells are responsible for tumour growth, metastasis, and cancer drug resistance. Inadequate response to conventional therapy in breast cancer leads researchers to find new treatment methods and literature surveys that support CSC studies. A selective anticancer agent BIBR1532 inhibits the telomerase enzyme. Many of the chemotherapeutic drugs used in clinical trials have harmful effects, but the advantage of telomerase-based inhibitors is that they are less toxic to healthy tissues. The phosphoinositide 3-kinase (PI3K)/serine/threonine kinase (Akt)/mammalian target of rapamycin (mTOR) pathway is common in breast cancer, and the interaction between the mTOR pathway and human telomerase reverse transcriptase (hTERT) is essential for the survival of cancer cells. In our study, we treated MCF-7, breast cancer stem cell (BCSC) and normal breast epithelial cell MCF10A with the BIBR1532 inhibitor. The IC 50 doses for the 48th hour of BIBR1532 treatment were detected as 34.59 μM in MCF-7, 29.91 μM in BCSCs, and 29.07 μM in MCF10A. It has been observed that this agent induces apoptosis in the BCSC and MCF-7 cell lines. According to the results of cell cycle analysis, G 2 /M phase accumulation was observed in BCSC and MCF-7 cell lines. It has also been shown that BIBR1532 suppresses telomerase activity in BCSC and MCF-7. The effect of BIBR1532 on the mTOR signalling pathway has been investigated for the first time in this study. It is thought that the telomerase inhibitor may bring a new approach to the treatment and it may be useful in the treatment of CSCs.

Keywords: BIBR1532; MCF-7; MCF10A; breast cancer stem cell; mTOR pathway; telomerase inhibitor.

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