Daurinol, a catalytic inhibitor of topoisomerase II alpha, suppresses SNU-840 ovarian cancer cell proliferation through cell cycle arrest in S phase
DC Field | Value | Language |
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dc.contributor.author | Kang, Kyungsu | - |
dc.contributor.author | Nho, Chu Won | - |
dc.contributor.author | Kim, Nam Doo | - |
dc.contributor.author | Song, Dae-Geun | - |
dc.contributor.author | Park, Young Gyun | - |
dc.contributor.author | Kim, Minkyun | - |
dc.contributor.author | Pan, Cheol-Ho | - |
dc.contributor.author | Shin, Dongyun | - |
dc.contributor.author | Oh, Seung Hyun | - |
dc.contributor.author | Oh, Ho-Suk | - |
dc.date.available | 2020-02-28T16:45:29Z | - |
dc.date.created | 2020-02-06 | - |
dc.date.issued | 2014-08 | - |
dc.identifier.issn | 1019-6439 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/12411 | - |
dc.description.abstract | Daurinol, a lignan from the ethnopharmacological plant Haplophyllum dauricum, was recently reported to be a novel topoisomerase II inhibitor and an alternative to the clinical anticancer agent etoposide based on a colorectal cancer model. In the present study, we elucidated the detailed biochemical mechanism underlying the inhibition of human topoisomerase II alpha by daurinol based on a molecular docking study and in vitro biochemical experiments. The computational simulation predicted that daurinol binds to the ATP-binding pocket of topoisomerase Ha. In a biochemical assay, daurinol (10-100 mu M) inhibited the catalytic activity of topoisomerase Ha in an ATP concentration-dependent manner and suppressed the ATP hydrolysis activity of the enzyme. However, daurinol did not inhibit topoisomerase I activity, most likely because topoisomerase I does not contain an ATP-binding domain. We also evaluated the anti-proliferative activity of daurinol in ovarian, small cell lung and testicular cancer cells, common target cancers treated with etoposide. Daurinol potently inhibited SNU-840 human ovarian cancer cell proliferation through cell cycle arrest in S phase, while etoposide induced G2/M phase arrest. Daurinol induced the increased expression of cyclin E, cyclin A and E2F-1, which are important proteins regulating S phase initiation and progression. Daurinol did not induce abnormal cell and nuclear enlargement in SNU-840 cells, in contrast to etoposide. Based on these data, we suggest that daurinol is a potential anticancer drug candidate for the treatment of human ovarian cancer with few side effects. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | SPANDIDOS PUBL LTD | - |
dc.relation.isPartOf | INTERNATIONAL JOURNAL OF ONCOLOGY | - |
dc.subject | ETOPOSIDE | - |
dc.subject | EXTENSION | - |
dc.subject | ENZYME | - |
dc.title | Daurinol, a catalytic inhibitor of topoisomerase II alpha, suppresses SNU-840 ovarian cancer cell proliferation through cell cycle arrest in S phase | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000338484600010 | - |
dc.identifier.doi | 10.3892/ijo.2014.2442 | - |
dc.identifier.bibliographicCitation | INTERNATIONAL JOURNAL OF ONCOLOGY, v.45, no.2, pp.558 - 566 | - |
dc.identifier.scopusid | 2-s2.0-84902583141 | - |
dc.citation.endPage | 566 | - |
dc.citation.startPage | 558 | - |
dc.citation.title | INTERNATIONAL JOURNAL OF ONCOLOGY | - |
dc.citation.volume | 45 | - |
dc.citation.number | 2 | - |
dc.contributor.affiliatedAuthor | Shin, Dongyun | - |
dc.contributor.affiliatedAuthor | Oh, Seung Hyun | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | daurinol | - |
dc.subject.keywordAuthor | topoisomerase II alpha inhibitor | - |
dc.subject.keywordAuthor | ovarian cancer | - |
dc.subject.keywordAuthor | ATP binding pocket | - |
dc.subject.keywordAuthor | secondary leukemia | - |
dc.subject.keywordPlus | ETOPOSIDE | - |
dc.subject.keywordPlus | EXTENSION | - |
dc.subject.keywordPlus | ENZYME | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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