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Molecules 2017, 22(4), 561; doi:10.3390/molecules22040561

Novel Palladium(II) Complexes that Influence Prominin-1/CD133 Expression and Stem Cell Factor Release in Tumor Cells

1
“I. Chiricuta” Institute of Oncology, Republicii 34-36, RO-400015 Cluj-Napoca, Romania
2
Medfuture Research Center for Advanced Medicine “Iuliu Hatieganu”, University of Medicine and Pharmacy, Babes 8, RO-400012 Cluj-Napoca, Romania
3
Department of Chemical Theory of Drugs, Faculty of Pharmacy, Comenius University in Bratislava, Kalinčiakova 8, 83104 Bratislava, Slovakia
4
Biotechnology Research Center, University of Agricultural Science and Veterinary Medicine, 400372 Cluj-Napoca, Romania
5
National Institute for Research and Development of Isotopic and Molecular Technologies, RO-400293 Cluj-Napoca, Romania
*
Author to whom correspondence should be addressed.
Academic Editors: Arnaud Gautier and Diego Muñoz-Torrero
Received: 20 February 2017 / Revised: 19 March 2017 / Accepted: 23 March 2017 / Published: 30 March 2017
View Full-Text   |   Download PDF [4740 KB, uploaded 17 April 2017]   |  

Abstract

New Pd(II) complexes of 1,7-bis(2-methoxyphenyl)hepta-1,6-diene-3,5-dione were synthesized and structurally characterized. The complexes were tested in vitro on human colon and hepatic carcinoma cell lines, normal hepatic cells and hematopoietic progenitor cells. Biological tests proved that Pd(II) complexes 1 and 2 (containing a curcumin derivative) exhibit a strong in vitro antitumor effect against the cells derived from human colorectal carcinoma and the hepatic metastasis of a colorectal carcinoma. Complex 1 has an outstanding inhibitory effect against BRAF-mutant colon carcinoma and hepatocarcinoma cell growth; 1 and 2 are both more active than the free ligand and have the capacity to trigger early apoptotic processes. By flow cytometric measurements, an important decrease of prominin-1 (CD133) molecule expression on tumor cells membrane was identified in cell populations subjected to 1 and 2. Quantitative immune enzymatic assay proved restrictions in stem cell factor (SCF) release by treated tumor cells. Although less cytotoxic, the free ligand inhibits the surface marker CD133 expression in hepatocarcinoma cells, and in HT-29 colon carcinoma. The new synthesized Pd(II) complexes 1 and 2 exhibit an important potential through their selective cytotoxic activity and by targeting the stem-like tumor cell populations, which leads to the tumor growth arrest and prevention of metastasis. View Full-Text
Keywords: palladium complexes; curcuminoids; colorectal cancer; prominin-1 expression; cytotoxicity; stem cell factor palladium complexes; curcuminoids; colorectal cancer; prominin-1 expression; cytotoxicity; stem cell factor
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Fischer-Fodor, E.; Mikláš, R.; Rišiaňová, L.; Cenariu, M.; Grosu, I.G.; Virag, P.; Perde-Schrepler, M.; Tomuleasa, C.; Berindan-Neagoe, I.; Devínsky, F.; Miklášová, N. Novel Palladium(II) Complexes that Influence Prominin-1/CD133 Expression and Stem Cell Factor Release in Tumor Cells. Molecules 2017, 22, 561.

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