Blocking antioxidants in cancer cells reduces tumor growth in mice Dec. 2, 2013 - Many cancers have adapted to cope with high levels of immune system-produced free radicals, also referred to as reactive oxygen species, by overproducing antioxidant proteins. One of these proteins, superoxide dismutase 1 (SOD1), is overproduced in lung adenocarcinomas and has been implicated as a target for chemotherapy. In this issue of the Journal of Clinical Investigation, Navdeep Chandel and colleagues from Northwestern University report the effects of a SOD1 pharmacological inhibitor on non-small-cell lung cancer (NSCLC) cells. The inhibitor, called ATN-224, stunted the growth of human NSCLC cells in culture and induced their death. The researchers also found that ATN-224 inhibited other antioxidant proteins, which caused high levels of hydrogen peroxide inside the cells. The ability of cancer cells to produce hydrogen peroxide was required for ATN-224-dependent effects, because hydrogen peroxide activated cell death pathways. Furthermore, ATN-224 induced cancer cell death and reduced tumor sizes in a mouse model of lung adenocarcinoma. ATN-224 dependent effects in animals were improved when the inhibitor was used in combination with another drug that activates programmed cell death. This study suggests inhibition of antioxidants may be a viable chemotherapeutic option. The above story is based on materials provided by Journal of Clinical Investigation, via EurekAlert!, a service of AAAS. Andrea Glasauer, Laura A. Sena, Lauren P. Diebold, Andrew P. Mazar, Navdeep S. Chandel. Targeting SOD1 reduces experimental non-small-cell lung cancer. Journal of Clinical Investigation, 2013; DOI: 10.1172/JCI71714