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PURITAN MEDICAL

Tumor Growth Blocked in Mice by Suppressing Antioxidants in Cancer Cells

By BiotechDaily International staff writers
Posted on 11 Dec 2013
Many cancers have adapted to deal with the 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 the December 2, 2013, issue of the Journal of Clinical Investigation, Dr. Navdeep Chandel and colleagues from Northwestern University (Evanston, IL, USA) reported the effects of a SOD1 pharmacologic suppressor on non-small-cell lung cancer (NSCLC) cells. The inhibitor, called ATN-224, blocked the growth of human NSCLC cells in culture, and triggered their death. The researchers also discovered that ATN-224 inhibited other antioxidant proteins, which caused high levels of hydrogen peroxide inside the cells. Cancer cells’ capability to generate hydrogen peroxide was required for ATN-224-dependent effects, because hydrogen peroxide activated cell death pathways.

ATN-224, moreover, triggered cancer cell death and decreased tumor sizes in a mouse model of lung adenocarcinoma. ATN-224-dependent effects in lab mice were enhanced when the inhibitor was used in combination with another drug that activates programmed cell death.

These new findings indicate that antioxidant suppression may be a feasible chemotherapeutic strategy.

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