Antiproliferative effects of phenylaminonaphthoquinones are increased by ascorbate and associated with the appearance of a senescent phenotype in human bladder cancer cells.

Quinone-containing molecules have been developed against cancer mainly for their redox cycling ability leading to reactive oxygen species (ROS) formation. We have previously shown that donor-acceptor phenylaminonaphthoquinones are biologically active against a panel of cancer cells. In this report, we explored the mechanisms involved in cancer cell growth inhibition caused by two phenylaminonaphthoquinones, namely Q7 and Q9, with or without ascorbate (ASC). The results show that Q7 and Q9 are both redox cyclers able to form ROS, which strongly inhibit the proliferation of T24 cells. Q9 was a better redox cycler than Q7 because of marked stabilization of the semiquinone radical species arising from its reduction by ascorbate. Indeed, ASC dramatically enhances the inhibitory effect of Q9 on cell proliferation. Q9 plus ASC impairs the cell cycle, causing a decrease in the number of cells in the G2/M phase without involving other cell cycle regulating key proteins. Moreover, Q9 plus ASC influences the MAPK signaling pathways, provoking the appearance of a senescent cancer cell phenotype and ultimately leading to necrotic-like cell death. Because cellular senescence limits the replicative capacity of cells, our results suggest that induction of senescence may be exploited as a basis for new approaches to cancer therapy.

Experimental determination of the radial dose distribution in high gradient regions around 192Ir wires: comparison of electron paramagnetic resonance imaging, films, and Monte Carlo simulations.

PURPOSE: The experimental determination of doses at proximal distances from radioactive sources is difficult because of the steepness of the dose gradient. The goal of this study was to determine the relative radial dose distribution for a low dose rate 192Ir wire source using electron paramagnetic resonance imaging (EPRI) and to compare the results to those obtained using Gafchromic EBT film dosimetry and Monte Carlo (MC) simulations. METHODS: Lithium formate and ammonium formate were chosen as the EPR dosimetric materials and were used to form cylindrical phantoms. The dose distribution of the stable radiation-induced free radicals in the lithium formate and ammonium formate phantoms was assessed by EPRI. EBT films were also inserted inside in ammonium formate phantoms for comparison. MC simulation was performed using the MCNP4C2 software code. RESULTS: The radical signal in irradiated ammonium formate is contained in a single narrow EPR line, with an EPR peak-to-peak linewidth narrower than that of lithium formate (approximately 0.64 and 1.4 mT, respectively). The spatial resolution of EPR images was enhanced by a factor of 2.3 using ammonium formate compared to lithium formate because its linewidth is about 0.75 mT narrower than that of lithium formate. The EPRI results were consistent to within 1% with those of Gafchromic EBT films and MC simulations at distances from 1.0 to 2.9 mm. The radial dose values obtained by EPRI were about 4% lower at distances from 2.9 to 4.0 mm than those determined by MC simulation and EBT film dosimetry. CONCLUSIONS: Ammonium formate is a suitable material under certain conditions for use in brachytherapy dosimetry using EPRI. In this study, the authors demonstrated that the EPRI technique allows the estimation of the relative radial dose distribution at short distances for a 192Ir wire source.