Anticancer Activity of Electron-Deficient Metal Complexes against Colorectal Cancer in vitro Models.

Autor: Azmanova M; School of Chemistry and Biosciences, University of Bradford, Richmond Road, BD7 1DP, Bradford, UK., Soldevila-Barreda J; School of Chemistry and Biosciences, University of Bradford, Richmond Road, BD7 1DP, Bradford, UK., Bani Hani H; School of Chemistry and Biosciences, University of Bradford, Richmond Road, BD7 1DP, Bradford, UK., Lord RM; School of Chemistry and Biosciences, University of Bradford, Richmond Road, BD7 1DP, Bradford, UK., Pitto-Barry A; School of Chemistry and Biosciences, University of Bradford, Richmond Road, BD7 1DP, Bradford, UK., Picksley SM; School of Chemistry and Biosciences, University of Bradford, Richmond Road, BD7 1DP, Bradford, UK., Barry NPE; School of Chemistry and Biosciences, University of Bradford, Richmond Road, BD7 1DP, Bradford, UK.
Jazyk: angličtina
Zdroj: ChemMedChem [ChemMedChem] 2019 Nov 20; Vol. 14 (22), pp. 1887-1893. Date of Electronic Publication: 2019 Oct 04.
DOI: 10.1002/cmdc.201900528
Abstrakt: An evaluation of the in vitro cytotoxicity of nine electron-deficient half-sandwich metal complexes towards two colorectal cancer cell lines (HCT116 p53+/+, HCT116 p53-/-) and one normal prostate cell line (PNT2) is presented herein. Three complexes were found to be equally cytotoxic towards both colorectal cancer cell lines, suggesting a p53-independent mechanism of action. These complexes are 12 to 34× more potent than cisplatin against HCT116 p53+/+ and HCT116 p53-/- cells. Furthermore, they were found to exhibit little or no cytotoxicity towards PNT2 normal cells, with selectivity ratios greater than 50. To gain an insight into the potential mechanisms of action of the most active compounds, their effects on the expression levels of a panel of genes were measured using qRT-PCR against treated HCT116 p53+/+ and HCT116 p53-/- cells, and cell-cycle analysis was carried out.
(© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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