國家衛生研究院 NHRI:Item 3990099045/1265
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    Title: Nonsteroidal anti-inflammatory drugs induce colorectal cancer cell apoptosis by suppressing 14-3-3 epsilon
    Authors: Liou, JY;Ghelani, D;Yeh, S;Wu, KK
    Contributors: Center for Cardiovascular and Blood Research
    Abstract: To determine the role of 14-3-3 in colorectal cancer apoptosis induced by nonsteroidal anti-inflammatory drugs (NSAIDs), we evaluated the effects of sulindac on 14-3-3 epsilon protein expression in colorectal cancer cells. Sulindac sulfide inhibited 14-3-3 epsilon proteins in HT-29 and DLD-1 cells in a time- and concentration-dependent manner. Sulindac sulfone at 600 mu mol/L inhibited 14-3-3 epsilon protein expression in HT-29. Indomethacin and SC-236, a selective cyclooxygenase-2 (COX-2) inhibitor, exerted a similar effect as sulindac. Sulindac suppressed 14-3-3 epsilon promoter activity. As 14-3-3 epsilon promoter activation is mediated by peroxisome proliferator-activated receptor delta (PPAR delta), we determined the correlation between 14-3-3 epsilon inhibition and PPAR delta suppression by NSAIDs. Sulindac sulfide inhibited PPAR delta protein expression and PPAR delta transcriptional activity. Overexpression of PPAR delta by adenoviral transfer rescued 14-3-3 epsilon proteins from elimination by sulindac or indomethacin. NSAID-induced 14-3-3e suppression was associated with reduced cytosolic Bad with elevation of mitochondrial Bad and increase in apoptosis which was rescued by Ad-PPAR8 transduction. Stable expression of 14-3-3 epsilon in HT-29 significantly protected cells from apoptosis. Our findings shed light on a novel mechanism by which NSAIDs induce colorectal cancer apoptosis via the PPAR delta/14-3-3 epsilon transcriptional pathway. These results suggest that 14-3-3 epsilon is a target for the prevention and therapy of colorectal cancer.
    Keywords: Oncology
    Date: 2007-04-01
    Relation: Cancer Research. 2007 Apr;67(7):3185-3191.
    Link to: http://dx.doi.org/10.1158/0008-5472.CAN-06-3431
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0008-5472&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000245622900036
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=34248174248
    Appears in Collections:[Kenneth Kun-Yu Wu] Periodical Articles

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