Reference - Detail
| RRC ID | 45372 |
|---|---|
| Author | Abe N, Hou DX, Munemasa S, Murata Y, Nakamura Y. |
| Title | Nuclear factor-kappaB sensitizes to benzyl isothiocyanate-induced antiproliferation in p53-deficient colorectal cancer cells. |
| Journal | Cell Death Dis |
| 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. |
| Volume | 5(11) |
| Pages | e1534 |
| Published | 2014-11-20 |
| DOI | 10.1038/cddis.2014.495 |
| PII | cddis2014495 |
| PMID | 25412312 |
| PMC | PMC4260753 |
| MeSH | Antineoplastic Agents, Phytogenic / pharmacology* Apoptosis / drug effects Cell Proliferation / drug effects Cyclin D1 / genetics Cyclin D1 / metabolism Gene Expression Regulation, Neoplastic* HCT116 Cells HT29 Cells Humans I-kappa B Kinase / genetics I-kappa B Kinase / metabolism Isothiocyanates / pharmacology* Phosphorylation / drug effects Promoter Regions, Genetic Protein Transport / drug effects RNA, Small Interfering / genetics RNA, Small Interfering / metabolism Signal Transduction Transcription Factor RelA / genetics* Transcription Factor RelA / metabolism Tumor Suppressor Protein p53 / antagonists & inhibitors Tumor Suppressor Protein p53 / genetics* Tumor Suppressor Protein p53 / metabolism beta Catenin / genetics beta Catenin / metabolism |
| IF | 6.304 |
| Times Cited | 21 |
| WOS Category | CELL BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 12 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | LoVo(RCB1639) |