TY - JOUR
T1 - Anticancer activity of electron-deficient metal complexes against colorectal cancer in vitro models
AU - Azmanova, Maria
AU - Soldevila‐Barreda, Joan
AU - Hani, Hira Bani
AU - Lord, Rianne M.
AU - Pitto‐Barry, Anaïs
AU - Picksley, Steven M.
AU - Barry, Nicolas P. E.
PY - 2019/11/20
Y1 - 2019/11/20
N2 - 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.
AB - 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.
UR - https://doi.org/10.1002/cmdc.201900528
U2 - 10.1002/cmdc.201900528
DO - 10.1002/cmdc.201900528
M3 - Article
VL - 14
SP - 1887
EP - 1893
JO - ChemMedChem
JF - ChemMedChem
SN - 1860-7179
IS - 22
ER -