The in vitro and in vivo Characterization of MATLyLu Prostate Cancer Cell Line to Combined Treatment with the NADPH Oxidase Inhibitor Apocynin and Ionizing Radiation

Abstract

<p>It has been observed that the radiation response of a cell line may positively correlate with baseline levels of reactive oxygen species (ROS) generation, which is facilitated, in part, by the function ofNADPH oxidase membrane proteins. Apocynin has been successfully used to inhibit ROS generation via NADPH oxidase for other uses. Here, the effectiveness of apocynin to improve sensitivity to radiation in the MATLyLu cell line was examined. MATLyLu-implanted Cop/Hsd rats undergoing lOGy/SfX radiation treatment demonstrated improved tumour control, as measured by survival time (to predetennined endpoints), when given apocynin orally throughout their radiation treatment, but not when given apocynin only before radiation. Rats given apocynin without radiation did not demonstrate improved survival over controls. MA TLyLu cells given apocynin in vitro, however, did not demonstrate improved response to radiation or a reduction in baseline ROS production on a per cell basis, and apocynin was found to inhibit growth when given alone. These contradictory in vivo and in vitro findings may be explained by certain proposed mechanisms of action for apocynin which requires it to be first synthesized into its dimer, diapocynin, before it will inhibit NADPH oxidase, and this synthesis may occur during ingestion. Further investigations with diapocynin and the MATLyLu cell line are required. Therefore the mechanism is uncertain, but it was concluded that apocynin and radiation administered together in vivo improves radiation response as compared to either treatment alone.</p>