start-ver=1.4
cd-journal=joma
no-vol=5
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2014
dt-pub=20141120
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Nuclear factor-kappaB sensitizes to benzyl isothiocyanate-induced antiproliferation in p53-deficient colorectal cancer cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Benzyl isothiocyanate (BITC), a dietary isothiocyanate derived from cruciferous vegetables, inhibits the proliferation of colorectal cancer cells, most of which overexpress β-catenin as a result of mutations in the genes for adenomatous polyposis coli or mutations in β-catenin itself. Because nuclear factor-κB (NF-κB) is a plausible target of BITC signaling in inflammatory cell models, we hypothesized that it is also involved in BITC-inhibited proliferation of colorectal cancer cells. siRNA-mediated knockdown of the NF-κB p65 subunit significantly decreased the BITC sensitivity of human colorectal cancer HT-29 cells with mutated p53 tumor suppressor protein. Treating HT-29 cells with BITC induced the phosphorylation of IκB kinase, IκB-α and p65, the degradation of IκB-α, the translocation of p65 to the nucleus and the upregulation of NF-κB transcriptional activity. BITC also decreased β-catenin binding to a positive cis element of the cyclin D1 promoter and thus inhibited β-catenin-dependent cyclin D1 transcription, possibly through a direct interaction between p65 and β-catenin. siRNA-mediated knockdown of p65 confirmed that p65 negatively affects cyclin D1 expression. On the other hand, when human colorectal cancer HCT-116 cells with wild-type p53 were treated with BITC, translocation of p65 to the nucleus was inhibited rather than enhanced. p53 knockout increased the BITC sensitivity of HCT-116 cells in a p65-dependent manner, suggesting that p53 negatively regulates p65-dependent effects. Together, these results identify BITC as a novel type of antiproliferative agent that regulates the NF-κB pathway in p53-deficient colorectal cancer cells.
en-copyright=
kn-copyright=

en-aut-name=AbeN
en-aut-sei=Abe
en-aut-mei=N
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=HouD-X
en-aut-sei=Hou
en-aut-mei=D-X
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MunemasaS
en-aut-sei=Munemasa
en-aut-mei=S
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MurataY
en-aut-sei=Murata
en-aut-mei=Y
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kn-aut-mei=
aut-affil-num=4
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en-aut-name=NakamuraY
en-aut-sei=Nakamura
en-aut-mei=Y
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

affil-num=1
en-affil=
kn-affil=Graduate School of Environmental and Life Science, Okayama University

affil-num=2
en-affil=
kn-affil=Department of Biochemical Science and Technology, Faculty of Agriculture, Kagoshima University

affil-num=3
en-affil=
kn-affil=Graduate School of Environmental and Life Science, Okayama University

affil-num=4
en-affil=
kn-affil=Graduate School of Environmental and Life Science, Okayama University

affil-num=5
en-affil=
kn-affil=Graduate School of Environmental and Life Science, Okayama University
END