title: Novel Palladium(II) Complexes that Influence Prominin-1/CD133 Expression and Stem Cell Factor Release in Tumor Cells.
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) complexes1and2(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. Complex1has an outstanding inhibitory effect against BRAF-mutant colon carcinoma and hepatocarcinoma cell growth;1and2are 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 to1and2. 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) complexes1and2exhibit 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.
authors.affiliation: "I. Chiricuta" Institute of Oncology, Republicii 34-36, RO-400015 Cluj-Napoca, Romania. fischer.eva@iocn.ro.|Medfuture Research Center for Advanced Medicine "Iuliu Hatieganu", University of Medicine and Pharmacy, Babes 8, RO-400012 Cluj-Napoca, Romania. fischer.eva@iocn.ro.
authors.forename: Eva
authors.initials: E
authors.lastname: Fischer-Fodor
authors.affiliation: Department of Chemical Theory of Drugs, Faculty of Pharmacy, Comenius University in Bratislava, Kalinčiakova 8, 83104 Bratislava, Slovakia. virag.piroska@yahoo.com.
authors.forename: Roman
authors.initials: R
authors.lastname: Mikláš
authors.affiliation: Department of Chemical Theory of Drugs, Faculty of Pharmacy, Comenius University in Bratislava, Kalinčiakova 8, 83104 Bratislava, Slovakia. pmariaida@yahoo.com.
authors.forename: Lucia
authors.initials: L
authors.lastname: Rišiaňová
authors.affiliation: Biotechnology Research Center, University of Agricultural Science and Veterinary Medicine, 400372 Cluj-Napoca, Romania. ciprian.tomuleasa@umfcluj.ro.
authors.forename: Mihai
authors.initials: M
authors.lastname: Cenariu
authors.affiliation: National Institute for Research and Development of Isotopic and Molecular Technologies, RO-400293 Cluj-Napoca, Romania. Ioana.neagoe@umfcluj.ro.
authors.forename: Ioana-Georgeta
authors.initials: IG
authors.lastname: Grosu
authors.affiliation: "I. Chiricuta" Institute of Oncology, Republicii 34-36, RO-400015 Cluj-Napoca, Romania. miklas@fpharm.uniba.sk.
authors.forename: Piroska
authors.initials: P
authors.lastname: Virag
authors.affiliation: "I. Chiricuta" Institute of Oncology, Republicii 34-36, RO-400015 Cluj-Napoca, Romania. lucia.risianova@gmail.com.
authors.forename: Maria
authors.initials: M
authors.lastname: Perde-Schrepler
authors.affiliation: "I. Chiricuta" Institute of Oncology, Republicii 34-36, RO-400015 Cluj-Napoca, Romania. devinsky@fpharm.uniba.sk.|Medfuture Research Center for Advanced Medicine "Iuliu Hatieganu", University of Medicine and Pharmacy, Babes 8, RO-400012 Cluj-Napoca, Romania. devinsky@fpharm.uniba.sk.
authors.forename: Ciprian
authors.initials: C
authors.lastname: Tomuleasa
authors.affiliation: "I. Chiricuta" Institute of Oncology, Republicii 34-36, RO-400015 Cluj-Napoca, Romania. Mihai.cenariu@usamvcluj.ro.|Medfuture Research Center for Advanced Medicine "Iuliu Hatieganu", University of Medicine and Pharmacy, Babes 8, RO-400012 Cluj-Napoca, Romania. Mihai.cenariu@usamvcluj.ro.
authors.forename: Ioana
authors.initials: I
authors.lastname: Berindan-Neagoe
authors.affiliation: Department of Chemical Theory of Drugs, Faculty of Pharmacy, Comenius University in Bratislava, Kalinčiakova 8, 83104 Bratislava, Slovakia. grosu.ioana@gmail.com.
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Devínsky
authors.affiliation: Department of Chemical Theory of Drugs, Faculty of Pharmacy, Comenius University in Bratislava, Kalinčiakova 8, 83104 Bratislava, Slovakia. miklasova@fpharm.uniba.sk.
authors.forename: Natalia
authors.initials: N
authors.lastname: Miklášová
mesh_terms: D000071916:AC133 Antigen / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms; D004354:Drug Screening Assays, Antitumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D008113:Liver Neoplasms; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010165:Palladium / Q000737:chemistry*; D019089:Stem Cell Factor / Q000378:metabolism*
chemical_list: D000071916:AC133 Antigen; D009942:Organometallic Compounds; C000606023:PROM1 protein, human; D019089:Stem Cell Factor; D010165:Palladium
keywords: colorectal cancer; curcuminoids; cytotoxicity; palladium complexes; prominin-1 expression; stem cell factor