A trans-platinum(II) complex induces apoptosis in cancer stem cells of breast cancer
Yükleniyor...
Dosyalar
Tarih
2017
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Pergamon-Elsevier Science Ltd
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
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.
Açıklama
Anahtar Kelimeler
Anti-Growth Effect, Apoptosis, Breast Cancer Stem Cells, Necroptosis, Platinum
Kaynak
Bioorganic & Medicinal Chemistry
WoS Q Değeri
Q2
Scopus Q Değeri
Q2
Cilt
25
Sayı
1
Künye
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
