ID | 53019 |
フルテキストURL | |
著者 |
Abe, N
Graduate School of Environmental and Life Science, Okayama University
Hou, D-X
Department of Biochemical Science and Technology, Faculty of Agriculture, Kagoshima University
Munemasa, S
Graduate School of Environmental and Life Science, Okayama University
ORCID
Murata, Y
Graduate School of Environmental and Life Science, Okayama University
ORCID
Kaken ID
publons
researchmap
Nakamura, Y
Graduate School of Environmental and Life Science, Okayama University
ORCID
Kaken ID
publons
researchmap
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抄録 | 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.
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発行日 | 2014-11-20
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出版物タイトル |
Cell Death and Disease
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巻 | 5巻
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ISSN | 2041-4889
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資料タイプ |
学術雑誌論文
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言語 |
英語
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著作権者 | Ⓒ2014 Macmillan Publishers Limited All rights reserved 2041-4889/14
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論文のバージョン | publisher
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査読 |
有り
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DOI |