Increase in thiol oxidative stress via glutathione reductase inhibition as a novel approach to enhance cancer sensitivity to X-ray irradiation.

Depletion of the reduced form of glutathione (GSH) has been extensively studied for its effect on sensitizing cancer to radiation. However, little is known about the effects of thiol oxidative stress created through an increase in glutathione disulfide (GSSG) on cancer sensitivity to radiation. In this study, an increase in GSSG was effectively created using 2-acetylamino-3-[4-(2-acetylamino-2-carboxyethylsulfanylthiocarbonylamino)phenylthiocarbamoylsulfanyl]propionic acid (2-AAPA), an irreversible glutathione reductase (GR) inhibitor.

Effects of glutathione reductase inhibition on cellular thiol redox state and related systems.

Although inhibition of glutathione reductase (GR) has been demonstrated to cause a decrease in reduced glutathione (GSH) and increase in glutathione disulfide (GSSG), a systematic study of the effects of GR inhibition on thiol redox state and related systems has not been noted. By employing a monkey kidney cell line as the cell model and 2-acetylamino-3-[4-(2-acetylamino-2-carboxy-ethylsulfanylthio carbonylamino)phenylthiocarbamoylsulfanyl]propionic acid (2-AAPA) as a GR inhibitor, an investigation of the effects of GR inhibition on cellular thiol redox state and related systems was conducted. Our study demonstrated that, in addition to a decrease in GSH and increase in GSSG, 2-AAPA increased the ratios of NADH/NAD(+) and NADPH/NADP(+).

Effects of dietary flaxseed on intestinal tumorigenesis in Apc(Min) mouse.

Dietary flaxseed has been shown to prevent azoxymethane (AOM)-induced colorectal cancers in male Fisher rats. The present study was designed to investigate the chemopreventive effects of dietary flaxseed on the development of intestinal tumors in Apc(Min) mice. Apc(Min) mice were divided into five different groups, fed with control (AIN-93M meal), corn meal, flaxseed meal, corn oil, and flaxseed oil supplemented diets.

Chemopreventive effects of dietary flaxseed oil on colon tumor development.

Fatty acid composition of dietary fat, primarily the levels of omega-3 and omega-6 polyunsaturated fatty acids, has shown profound effect on colon tumor development in animal studies. Fats containing omega-6 fatty acids (for example, corn oil) enhanced and omega-3 fatty acids (for example, fish oil and mustard oil) reduced chemically induced colon tumors in rats. The purpose of this study was to investigate the effects of dietary flaxseed oil (containing alpha-linolenic acid, an omega-3 polyunsaturated fatty acid) on azoxymethane-induced colon tumor in rats and how it compared with the dietary corn oil-treated group.