DNA damage induction and antiproliferative activity of vanadium(V) oxido monoperoxido complex containing two bidentate heteroligands

Abstract

Several peroxidovanadium(V) complexes have been shown as a potent anticancer agents. The aim of this study was to investigate the interaction of monoperoxidovanadium(V) complex Pr4N[VO(O2)(ox)(phen)], (Vphen), [phen=1,10-phenantroline, ox=oxalate(2−) and Pr4N=tetra(n-propyl)ammonium(1+)] with DNA. UV–Vis spectrophotometry and the alkaline single-cell gel electrophoresis (SCGE, the comet assay) were used to examine the possibility of the vanadium(V) complex to induce changes in DNA. The interaction of Vphen with calf thymus DNA resulted in absorption hyperchromicity in DNA spectrum and shift of the absorption band of DNA to longer wavelengths for the [complex]/[DNA] concentration ratio equals to 4 and after 60min of incubation. The rise in DNA absorption (by 34%) and bathochromic shift (Δλmax=6nm) are indicative of the interaction between DNA and the complex molecules. DNA strand breaks in cellular DNA were investigated using the comet assay. The human lymphocytes were exposed to various concentrations of Vphen for 30min. The results revealed that Vphen contributed to the DNA damage expressed as DNA strand breaks in concentration dependent manner. The used concentrations of Vphen (ranging from 0.1 to 100μmol/L) caused higher DNA damage in lymphocytes compared to untreated cells (from 1.2 times for 0.1μmol/L to 1.8 times for 100μmol/L). Vphen was screened for its potential antitumor activity towards murine leukemia cell line L1210. Vphen exhibited significant antiproliferative activity depending on its concentration and time of exposure. The IC50 values were 0.247μg/mL (0.45μmol/L) for 24h, 0.671μg/mL (1.21μmol/L) for 48h and 0.627μg/mL (1.13μmol/L) for 72h.