Increase in oxidative stress via glutathione reductase inhibition as a novel approach to enhance cancer sensitivity to radiation

MEDI 341

Yong Zhao, yzhao1788@jacks.sdstate.edu, Teresa Seefeldt, Teresa.Seefeldt@sdstate.edu, Wei Chen, Laura Carlson, Adam Stoebner, Sarah Hanson, Ryan Foll, Srinath Palakurthi, and Xiangming Guan. Department of Pharmaceutical Sciences, South Dakota State University, Brookings, SD 57007
Radiation is one of the major therapies in cancer treatment. The main obstacle in treating cancer by radiation is cancer resistance. Therefore, developing novel approaches to reverse cancer resistance or to increase cancer sensitivity to radiation is an ongoing research effort. In this poster, we would like to report that an increase in oxidative stress by inhibition of glutathione reductase (GR) significantly increased the sensitivity of OVCAR-3 cells, a human ovarian cancer cell line, to radiation. When the cells were treated with 2-acetylamino-3-[4-(2-acetylamino-2-carboxyethylsulfanylthiocarbonyl-amino)phenylthiocarbamoylsulfanyl]propionic acid (2-AAPA), an irreversible GR inhibitor developed in this laboratory, followed by radiation in a 96 well plate, a significant synergistic effect was observed suggesting that inhibition of GR could be a novel approach to increase ovarian cancer sensitivity to radiation. The synergistic effect was correlated with an increase in cell oxidative stress which was measured by the levels of intracellular reduced glutathione and oxidized glutathione.
 

Poster Session
7:00 PM-9:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Medicinal Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007