Transcriptional induction of Nur77 by indomethacin that results in apoptosis of colon cancer cells

Non-steroidal anti-inflammatory drugs (NSAIDs) have cancer preventive and t umor regressive effects in the human colon, perhaps due to their capability to induce apoptosis of the colon cancer cells. Here, we report that indome thacin induced the expression of Nur77 which has been implicated in activat ion-induced apoptosis of T-lymphocytes, in a colon cancer cell line, HCT-15 . The transcript- and protein-level, the transcriptional activity of Nur77 promoter, and the DNA binding of Nur77 were significantly induced following indomethacin treatment. Among the two potential trans-acting factors that activate Nur77-promoter, indomethacin induced DNA binding and reporter gene activity of AP-1, but not that of related serum response factor (RSRF), su ggesting that the transcriptional induction of Nur77 may be mediated throug h activation of AP-1, Further, we showed that all-trans-RA repressed the in duction of Nur77 as well as the apoptosis-induced by indomethacin, providin g evidence that transcriptional induction of Nur77 may be an important mech anism by which indomethacin induces apoptosis in colon cancer cells.