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A trans-platinum(II) complex induces apoptosis in cancer stem cells of breast cancer

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Date

2017

Author

Aztopal, Nazlihan
Karakas, Didem
Cevatemre, Buse
Ari, Ferda
Icsel, Ceyda
Daidone, Maria G.
Ulukaya, Engin

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Citation

Aztopal, N., Karakas, D., Cevatemre, B., Ari, F., Icsel, C., Daidone, M. G., & Ulukaya, E. (2017). A trans-platinum(II) complex induces apoptosis in cancer stem cells of breast cancer. Bioorganic and Medicinal Chemistry, 25(1), 269–276. https://doi.org/10.1016/j.bmc.2016.10.032

Abstract

Recent accumulating evidence has supported the notion that tumors have hierarchically organized heterogeneous cell populations and a small subpopulation of cells, termed cancer stem cells (CSCs), are responsible for tumor initiation, maintenance as well as drug resistance. Therefore, targeting the CSCs along with the other cancer cells has been the most important topic during the last decade. In the present study, we evaluated the cytotoxic activity of trans-[PtCl2(2-hepy) 2] [2-hepy = 2-(2-hydroxyethyl) pyridine] complex and the mechanism of cell death in breast CSCs. Stemness markers, Oct-4 and Sox2, were determined in mammospheres by western blotting. Cytotoxicity was assessed using the ATP viability assay. Cell death was fluorescently visualized and further confirmed by flow cytometry as well as gene expression analysis. The Pt(II) complex significantly reduced the cell viability, prevented mammosphere formation and disrupted mammosphere structures in a dose-dependent manner (0100 lM). The mode of cell death was apoptosis and it was shown by the presence of caspase 3/7 activity, Annexin V-FITC positivity, decreased mitochondrial membrane potential and increased expressions of pro-apoptotic genes (TNFRSF10A and HRK). Interestingly, necroptosis was also observed by the evidence of increased MLKL expression. In conclusion, the Pt(II) complex seems to be a highly promising anticancer compound due to its promising cytotoxic activity on CSCs. Therefore, it deserves in vivo further studies for the proof-of-concept. (C) 2016 Elsevier Ltd. All rights reserved.

Source

Bioorganic & Medicinal Chemistry

Volume

25

Issue

1

URI

https://doi.org/10.1016/j.bmc.2016.10.032
https://hdl.handle.net/20.500.12713/923

Collections

  • PubMed İndeksli Yayınlar Koleksiyonu [1153]
  • Scopus İndeksli Yayınlar Koleksiyonu [1892]
  • Temel Tıp Bilimleri Bölümü Makale Koleksiyonu [235]
  • WoS İndeksli Yayınlar Koleksiyonu [1970]



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