Both NFκB and AP-1 are well characterized families of transcription factors that are involved in many disease states, including cancer, diabetes, and Alzheimer's disease. It is well known that these transcription factors are prosurvival and proinflammatory factors and are therefore considered promising targets for development of new therapeutics. Recent research has focused on curcumin as an inhibitor of the activation of both NFκB and AP-1. Curcumin is a natural product utilized throughout the world as a spice, a paste for wounds, as well as being used for many autoimmune diseases, such as rheumatoid arthritis. In addition, it has powerful antioxidant activity. Previous research from our laboratory has focused on the abilities of curcumin as its analogues to inhibit the activation of NFκB. The focus of the present work was to test curcumin and its analogues as inhibitors of the activation of AP-1 and whether activation of AP-1 and NFκB is inhibited by the same analogues, which might point towards a common target. Curcumin and 84 analogues were tested by using AP-1 293 cell line co transfected with a luciferase reporter. Cells were then induced with PMA (phorbol 12-myristate 13-acetate) and inhibition of NFκB and AP-1 was then assayed with a luminometer. The seven most active inhibitory compounds were the same for both AP-1 and NFκB. In addition, some of the compounds acted to enhance the activation of AP-1. The results of this research indicate that there may be a common upstream target for both NFκB and AP-1. Further research will serve to better understand the activation and inhibition of these proinflammatory and oncogenic transcription families.
This work supported in part by NIH grant EY13695 from the National Eye Institute and grant BC043125 from the US Army/DOD Breast Cancer Program.
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