title: Metal Zn(II), Cu(II), Ni (II) complexes of ursodeoxycholic acid as putative anticancer agents.
abstract: The aim of the study was to evaluate the influence of metal [Zn(II), Cu(II), Ni(II)] complexes with ursodeoxycholic acid (UDCA) on the viability and proliferation of tumour and non-tumour cells. Cell lines established from retrovirus-transformed chicken hepatoma (LSCC-SF-Mc29) and rat sarcoma (LSR-SF-SR) as well as from human cancers of the breast (MCF-7), uterine cervix (HeLa), lung (A549) and liver (HepG2) were used as model systems. Non-tumour human embryo (Lep-3) cells were also included in some of the experiments. The investigations were carried out by the thiazolyl blue tetrazolium bromide (MTT) test, neutral red uptake cytotoxicity assay, crystal violet staining, double staining with acridine orange and propidium iodide and the colony-forming method. The results obtained revealed that: (1) UDCA and its metal complexes in the tested concentrations decreased (to a varying degree) the viability and proliferation of the treated cells in a time- and concentration-dependent manner; (2) chicken hepatoma (LSCC-SF-Mc29) cells were most sensitive to the cytotoxic and antiproliferative action of the compounds tested, followed by rat sarcoma (LSR-SF-SR) cells; (3) Cu‒UDCA and Ni‒UDCA were more effective against animal LSCC-SF-Mc29 and LSR-SF-SR cells, while Zn‒UDCA significantly decreased the viability and proliferation of human tumour cell lines; (4) applied independently, UDCA expressed lower cytotoxic/cytostatic activity as compared to metal complexes; and (5) the sensitivity of the non-tumour embryonic Lep-3 cells to the effects of UDCA and its metal complexes was comparable or even higher than those of the human tumour cells.
authors.affiliation: Institute of Neurobiology, Department of Synaptic Signaling and Communications, Bulgarian Academy of Sciences , Sofia , Bulgaria.
authors.forename: Lora
authors.initials: L
authors.lastname: Dyakova
authors.affiliation: Institute of Physical Chemistry 'Ilie Murgulescu', Romanian Academy , Bucharest , Romania.
authors.forename: Daniela-Cristina
authors.initials: DC
authors.lastname: Culita
authors.affiliation: Institute of Physical Chemistry 'Ilie Murgulescu', Romanian Academy , Bucharest , Romania.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Marinescu
authors.affiliation: Institute of Experimental Morphology, Pathology and Anthropology with Museum, Department of Pathology, Bulgarian Academy of Sciences , Sofia , Bulgaria.
authors.forename: Marin
authors.initials: M
authors.lastname: Alexandrov
authors.affiliation: Institute of Neurobiology, Department of Synaptic Signaling and Communications, Bulgarian Academy of Sciences , Sofia , Bulgaria.
authors.forename: Reni
authors.initials: R
authors.lastname: Kalfin
authors.affiliation: Institute of Physical Chemistry 'Ilie Murgulescu', Romanian Academy , Bucharest , Romania.
authors.forename: Luminita
authors.initials: L
authors.lastname: Patron
authors.affiliation: Institute of Experimental Morphology, Pathology and Anthropology with Museum, Department of Pathology, Bulgarian Academy of Sciences , Sofia , Bulgaria.
authors.forename: Radostina
authors.initials: R
authors.lastname: Alexandrova
keywords: cell lines; cytotoxic/cytostatic activity; metal complexes; pharmaceutical biotechnology; ursodeoxycholic acid