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NSAID‐activated gene‐1 as a molecular target for capsaicin‐induced apoptosis through a novel molecular mechanism involving GSK3beta, C/EBPbeta, and ATF3
Author(s) -
Lee SeongHo,
Krisanapun Chutwadee,
Baek Seung Joon
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.928.11
Subject(s) - transactivation , capsaicin , apoptosis , cancer research , chemistry , atf3 , microbiology and biotechnology , gene knockdown , gene expression , gene , biology , promoter , biochemistry , receptor
NSAID‐activated gene‐1 (NAG‐1) is a cytokine associated with pro‐apoptotic and anti‐tumorigenic property in colon and lung cancer. Capsaicin, a natural product of the Capsicum species of red peppers, is known to induce apoptosis in colon cancer cells. This study was performed to determine molecular mechanism by which capsaicin activates transactivation of NAG‐1 gene in human colorectal cancer cells. Capsaicin increases apoptosis, and up‐regulates NAG‐1 gene expression at the transcriptional level through C/EBPbeta‐mediated pathway. We identified C/EBPbeta binding sites in the NAG‐1 promoter responsible for capsaicin‐induced NAG‐1 transactivation and EMSA and ChIP assay confirmed binding of C/EBPbeta to the NAG‐1 promoter. Capsaicin treatment increased C/EBPbeta phosphorylation, and enhanced binding of C/EBPbeta with GSK3beta, and ATF3. Knockdown of C/EBPbeta, GSK3beta or ATF3 ameliorates NAG‐1 expression induced by capsaicin treatment. These data indicate that C/EBPbeta phosphorylation through binding to GSK3beta may mediate capsaicin‐induced expression of NAG‐1 and apoptosis through cooperation with ATF3 in human colorectal cancer cells. Grant Funding Source : NIH, American Cancer Society