Anti-Cancer Activity of a Novel Small Molecule Compound That Simultaneously Activates p53 and Inhibits NF-kappa B Signaling
DC Field | Value | Language |
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dc.contributor.author | Hwang, Sun Gwan | - |
dc.contributor.author | Park, Jinah | - |
dc.contributor.author | Park, Joo Young | - |
dc.contributor.author | Park, Cheol Hyoung | - |
dc.contributor.author | Lee, Ki-Ho | - |
dc.contributor.author | Cho, Jeong Woo | - |
dc.contributor.author | Hwang, Jong-Ik | - |
dc.contributor.author | Seong, Jae Young | - |
dc.date.accessioned | 2021-09-06T15:40:43Z | - |
dc.date.available | 2021-09-06T15:40:43Z | - |
dc.date.created | 2021-06-18 | - |
dc.date.issued | 2012-09-13 | - |
dc.identifier.issn | 1932-6203 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/107463 | - |
dc.description.abstract | The p53 and NF-kappa B pathways play important roles in diverse cellular functions, including cell growth, apoptosis, and tumorigenesis. Mutations that inactivate the p53 gene and constitutive NF-kappa B pathway activation are common occurrences in human cancers. Although many drugs are being developed that selectively activate p53 or inhibit NF-kappa B, there are few drug candidates that can do both. Simultaneous activation of p53 and inhibition of the NF-kappa B pathway is therefore a prime target for new cancer drug development. This study is the first report of a high-throughput approach with mass compounds that concurrently target both pathways. Using a cell-based screening assay and a library of 200,000 synthetic compounds, we identified 9 small molecules that simultaneously inhibit NF-kappa B and activate p53. One of these compounds, N-2, increased the expression of p53 target genes, including p21 and GADD45a. In addition, N-2 inhibited the transcriptional activity of NF-kappa B, concomitantly repressing interleukin-6 and monocyte chemotactic protein-1 (MCP-1) expression. When cell lines derived from a diverse range of cancers were treated in vitro with N-2, we observed increased cell death. N-2 also significantly inhibited allograft growth in murine models of melanoma and lung carcinoma. Our findings suggest that N-2 may act as a bivalent anti-cancer agent through simultaneous modulation of NF-kappa B and p53 activities. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | PUBLIC LIBRARY SCIENCE | - |
dc.subject | ANCHORAGE-INDEPENDENT GROWTH | - |
dc.subject | TRANSCRIPTION FACTOR | - |
dc.subject | INDUCED PHOSPHORYLATION | - |
dc.subject | SESQUITERPENE LACTONE | - |
dc.subject | CELL-GROWTH | - |
dc.subject | CANCER | - |
dc.subject | APOPTOSIS | - |
dc.subject | RAS | - |
dc.subject | REQUIREMENT | - |
dc.subject | SUPPRESSION | - |
dc.title | Anti-Cancer Activity of a Novel Small Molecule Compound That Simultaneously Activates p53 and Inhibits NF-kappa B Signaling | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Hwang, Jong-Ik | - |
dc.contributor.affiliatedAuthor | Seong, Jae Young | - |
dc.identifier.doi | 10.1371/journal.pone.0044259 | - |
dc.identifier.scopusid | 2-s2.0-84866394311 | - |
dc.identifier.wosid | 000308788700017 | - |
dc.identifier.bibliographicCitation | PLOS ONE, v.7, no.9 | - |
dc.relation.isPartOf | PLOS ONE | - |
dc.citation.title | PLOS ONE | - |
dc.citation.volume | 7 | - |
dc.citation.number | 9 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.subject.keywordPlus | ANCHORAGE-INDEPENDENT GROWTH | - |
dc.subject.keywordPlus | TRANSCRIPTION FACTOR | - |
dc.subject.keywordPlus | INDUCED PHOSPHORYLATION | - |
dc.subject.keywordPlus | SESQUITERPENE LACTONE | - |
dc.subject.keywordPlus | CELL-GROWTH | - |
dc.subject.keywordPlus | CANCER | - |
dc.subject.keywordPlus | APOPTOSIS | - |
dc.subject.keywordPlus | RAS | - |
dc.subject.keywordPlus | REQUIREMENT | - |
dc.subject.keywordPlus | SUPPRESSION | - |
dc.subject.keywordAuthor | ANCHORAGE-INDEPENDENT GROWTH | - |
dc.subject.keywordAuthor | DNA-DAMAGE | - |
dc.subject.keywordAuthor | TRANSCRIPTION FACTOR | - |
dc.subject.keywordAuthor | CELL-GROWTH | - |
dc.subject.keywordAuthor | INDUCED PHOSPHORYLATION | - |
dc.subject.keywordAuthor | SESQUITERPENE LACTONE | - |
dc.subject.keywordAuthor | CANCER-THERAPY | - |
dc.subject.keywordAuthor | LUNG-CANCER | - |
dc.subject.keywordAuthor | APOPTOSIS | - |
dc.subject.keywordAuthor | MDM2 | - |
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