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

Title The in vitro renal cell toxicity of some unconventional anticancer phenanthroline-based platinum(II) complexes.
Authors N.S. Ng; M.J. Wu; S.J. Myers; J.R. Aldrich-Wright
Journal J Inorg Biochem
DOI 10.1016/j.jinorgbio.2017.11.021

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 1.7-25?M) than in A2780 ovarian cancer cells or cisplatin-resistant A2780cisR cells (IC50 0.2-2.1?M) (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 (90?M). PHENSS induced an elongated renal cell morphology, cytoskeletal stress fibre thickening, and increased ?-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, cellular enlargement, G2/M arrest and apoptosis. The cytotoxicity of all platinum(II) complexes in both renal and ovarian cell lines were reduced in the presence of organic cation transporter (OCT) inhibitors cimetidine, disopyramide and amantadine. PHENSS and analogues demonstrated low level genotoxicity in an in vitro micronuclei assay compared to cisplatin or etoposide. These findings highlight PHENSS and other phen-based unconventional platinum(II) complexes as promising anticancer agents with alternative modes of action that induce lower kidney cell toxicity and genotoxicity, while demonstrating greater cisplatin-resistant ovarian cancer cell toxicity.

Citation N.S. Ng; M.J. Wu; S.J. Myers; J.R. Aldrich-Wright.The in vitro renal cell toxicity of some unconventional anticancer phenanthroline-based platinum(II) complexes.. J Inorg Biochem. 2018;179:97106. doi:10.1016/j.jinorgbio.2017.11.021

Related Elements


See more Platinum products. Platinum (atomic symbol: Pt, atomic number: 78) is a Block D, Group 10, Period 6 element with an atomic weight of 195.084. The number of electrons in each of platinum's shells is [2, 8, 18, 32, 17, 1] and its electron configuration is [Xe] 4f14 5d9 6s1. The platinum atom has a radius of 139 pm and a Van der Waals radius of 175 pm. Platinum Bohr ModelElemental PlatinumPlatinum was discovered and first isolated by Antonio de Ulloa in 1735. It is one of the rarest elements in the earth's crust, occurring at a concentration of only 0.005 ppm. Platinum is found uncombined as a free element and alloyed with iridium as platiniridium. In its elemental form, platinum has a grayish white appearance. It is highly resistant to corrosion: the metal does not oxidize in air at any temperature. It is generally non-reactive, even at high temperatures. The origin of the name "platinum" comes from the Spanish word platina, meaning silver.

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