The in vitro renal cell toxicity of some unconventional anticancer phenanthroline-based platinum(II) complexes.

The in vitro renal cell toxicity of some unconventional anticancer phenanthroline-based platinum(II) complexes.
J Inorg Biochem. 2017 Nov 30;179:97-106
Authors: Ng NS, Wu MJ, Myers SJ, Aldrich-Wright JR
Abstract
The cytotoxicity of platinum(II) complexes coordinated to a chiral diamine, 1S,2S-diaminocyclohexane or 1R,2R-diaminocyclohexane and 1,10-phenanthroline or 3,4,7,8-tetramethyl-1,10-phenanthroline has been investigated in the renal proximal tubule HK-2 cell line. All platinum(II) complexes exhibited lower cytotoxicity in HK-2 cells (IC50 1.7-25μM) than in A2780 ovarian cancer cells or cisplatin-resistant A2780cisR cells (IC50 0.2-2.1μM) (at 48h). PHENSS ([Pt(1,10-phenanthroline)(1S,2S-dach)]2+) induced apoptosis and necrosis in ovarian cancer cells at concentrations that are relatively cytostatic to renal cells. Cisplatin was similarly or more cytotoxic to renal cells than ovarian cancer cells. Similar trends were reflected with shorter term exposure (1.5h). PHENSS demonstrated a comparatively cytostatic mode of action in renal cell cultures than cisplatin, as demonstrated by lower toxicity at higher concentrations (90μM). PHENSS induced an elongated renal cell morphology, cytoskeletal stress fibre thickening, and increased β-galactosidase activity, but no detectable change in reactive oxygen species generation or cell cycle distribution. In contrast, cisplatin treatment was associated with increased oxidative stress, cell...

Source: Journal of Inorganic Biochemistry - November 30, 2017 Category: Biochemistry Authors: Ng NS, Wu MJ, Myers SJ, Aldrich-Wright JR Tags: J Inorg Biochem Source Type: research