1. Addition Of Niclosamide To Palladium(Ii) Saccharinate Complex Of Terpyridine Results In Enhanced Cytotoxic Activity Inducing Apoptosis On Cancer Stem Cells Of Breast Cancer
- Author
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Veysel T. Yilmaz, Ferda Ari, Didem Karakas, Engin Ulukaya, Buse Cevatemre, Nazlihan Aztopal, Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü., Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Kimya Bölümü., Uludağ Üniversitesi/Tıp Fakültesi/Klinik Biyokimya Anabilim Dalı., Karakaş, Didem, Cevatemre, Buse, Aztopal, Nazlıhan, Arı, Ferda, Yılmaz, Veysel Turan, Ulukaya, Engin, L-6687-2018, K-5792-2018, AHD-2050-2022, L-7238-2018, L-6682-2018, AAG-7012-2021, and AAV-4886-2020
- Subjects
Platinum(II) complexes ,Unclassified drug ,Biochemistry & molecular biology ,Cytotoxicity ,Pyridine ,Clinical Biochemistry ,Enzyme linked immunosorbent assay ,Pharmaceutical Science ,Assay ,Apoptosis ,Pharmacology ,Real time polymerase chain reaction ,Biochemistry ,Gene ,Palladium(II) complex ,Agent ,Targeted therapy ,In-vitro ,Gene overexpression ,Breast cancer ,ATP viability assay ,TNFRSF10A gene ,Drug Discovery ,Breast cancer stem cell ,Pathology ,Cytotoxic T cell ,Cancer inhibition ,Flow cytometry ,Wnt Signaling Pathway ,Chemistry, organic ,Inhibition ,Hermes antigen ,ATG5 gene ,Fluorescence microscopy ,biology ,Chemistry ,Wnt signaling pathway ,Palladium saccharinate complex ,Vivo ,Necroptosis ,Palladium complex ,Neoplastic Stem Cells ,Molecular Medicine ,Niclosamide ,Female ,Autophagy protein 5 ,Stem cell ,Chemistry, medicinal ,Palladium ,Human ,CD24 antigen ,Cell death ,Programmed cell death ,Drug cytotoxicity ,Drug potentiation ,Breast Neoplasms ,FAS gene ,Article ,Cancer stem cell ,Upregulation ,Autophagy ,Humans ,Viability assay ,Terpyridine ,Molecular Biology ,Antigen expression ,Tumors ,Antineoplastic activity ,Drug effects ,Pharmacology & pharmacy ,Organic Chemistry ,CD44 ,Carcinoma ,Fas antigen ,Complex ,2-Phenylpyridine ,Drug efficacy ,MLKL gene ,biology.protein ,Cancer research ,Antitumor-activity ,Controlled study - Abstract
Wnt signaling is one of the core signaling pathways of cancer stem cells (CSCs). It is re-activated in CSCs and plays essential role in the survival, self-renewal and proliferation of these cells. Therefore, we aimed to evaluate the cytotoxic effects of palladium(II) complex which is formulated as [PdCl(terpy)](sac)2H(2)O and its combination with niclosamide which is an inhibitor of Wnt signaling pathway associated with breast cancer stem cells. Characteristic cell surface markers (CD44(+)/CD24(-)) were determined by flow cytometry in CSCs. ATP viability assay was used to determine the cytotoxic activity. The mode of cell death was evaluated morphologically using fluorescence microscopy and biochemically using M30 ELISA assay as well as performing qPCR. Our study demonstrated that the combination of niclosamide (1.5 mu M) and Pd(II) complex (12.5, 25 and 50 mu M) at 48 h has enhanced cytotoxic activity resulted from the induction of apoptosis (indicated by the presence of pyknotic nuclei, increments in M30 and over expression of proapoptotic genes of TNFRSF10A and FAS). Importantly, the addition of niclosamide resulted in the suppression of autophagy (proved by the decrease in ATG5 gene levels) that might have contributed to the enhanced cytotoxicity. In conclusion, the application of this combination may be regarded as a novel and effective approach for the treatment of breast cancer due to its promising cytotoxic effect on cancer stem cells that cause recurrence of the disease. (C) 2015 Elsevier Ltd. All rights reserved.
- Published
- 2015