"Targeting the cellular redox environment in the treatment of lymphoma"
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Abstract: The cellular redox environment is determined from the balance between the production of prooxidant species and the removal of these by antioxidant defenses. Evidence that the cellular redox environment impacts the risk of cancer includes: 1) environmental toxins that generate prooxidants in cells can initiate and promote carcinogenesis; 2) chronic inflammation and infections that produce a prooxidant state are associated with the development of cancer; and 3) an increased intake of dietary antioxidants is associated with a reduced cancer incidence. Lymphoma is a cancer of lymphocytes; these cells play a vital role in the immune system. Working in collaboration with other research groups, my laboratory has investigated the mechanisms by which an altered redox environment in lymphoma cells confers cancer phenotypes. Microarray analyses of 240 lymphoma tumor specimens showed a significant correlation between altered expression of redox-related genes and short survival time following standard therapy. Our results from in vitro studies clearly show that the sensitivity of lymphoma cells to chemotherapy-induced apoptosis depends on the cellular redox environment. Lymphoma cells with an altered redox environment show changes in glucose metabolism and in the expression of genes regulated by redox-sensitive transcription factors. Levels of the Bcl-2 family of proteins are not significantly altered. Preliminary data indicate that drugs which target the cellular redox environment may well improve the efficacy of lymphoma treatments.