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dc.contributor.authorManu, K.
dc.contributor.authorShanmugam, M.
dc.contributor.authorOng, T.
dc.contributor.authorSubramahniam, A.
dc.contributor.authorSiveen, K.
dc.contributor.authorPerumal, E.
dc.contributor.authorSamy, R.
dc.contributor.authorBist, P.
dc.contributor.authorLim, L.
dc.contributor.authorKumar, Alan Prem
dc.contributor.authorHui, K.
dc.contributor.authorSethi, G.
dc.date.accessioned2017-01-30T10:55:43Z
dc.date.available2017-01-30T10:55:43Z
dc.date.created2013-03-18T20:00:47Z
dc.date.issued2013
dc.date.submitted2013-11-14
dc.identifier.citationManu, Kanjoormana Aryan and Shanmugam, Mathu K. and Ong, Tina H. and Subramahniam, Aruljothi and Siveen, Kodappullly Sivaraman and Perumal, Ekambaram and Samy, Ramar Perumal and Bist, Pradeep and Lim, Lina H.K. and Kumar, Alan Prem and Hui, Kam M. and Sethi, Gautam. 2013. Emodin suppresses migration and invasion through the modulation of CXCR4 expression in an orthotopic model of human hepatocellular carcinoma. PLoS ONE. 8 (3): pp. e57015.
dc.identifier.urihttp://hdl.handle.net/20.500.11937/6812
dc.identifier.doi10.1371/journal.pone.0057015
dc.description.abstract

Accumulating evidence(s) indicate that CXCL12-CXCR4 signaling cascade plays an important role in the process of invasion and metastasis that accounts for more than 80% of deaths in hepatocellular carcinoma (HCC) patients. Thus, identification of novel agents that can downregulate CXCR4 expression and its associated functions have a great potential in the treatment of metastatic HCC. In the present report, we investigated an anthraquinone derivative, emodin for its ability to affect CXCR4 expression as well as function in HCC cells. We observed that emodin downregulated the expression of CXCR4 in a dose-and time-dependent manner in HCC cells. Treatment with pharmacological proteasome and lysosomal inhibitors did not have substantial effect on emodin-induced decrease in CXCR4 expression. When investigated for the molecular mechanism(s), it was observed that the suppression of CXCR4 expression was due to downregulation of mRNA expression, inhibition of NF-κB activation, and abrogation of chromatin immunoprecipitation activity. Inhibition of CXCR4 expression by emodin further correlated with the suppression of CXCL12-induced migration and invasion in HCC cell lines. In addition, emodin treatment significantly suppressed metastasis to the lungs in an orthotopic HCC mice model and CXCR4 expression in tumor tissues. Overall, our results show that emodin exerts its anti-metastatic effect through the downregulation of CXCR4 expression and thus has the potential for the treatment of HCC.

dc.publisherPublic Library of Science
dc.titleEmodin suppresses migration and invasion through the modulation of CXCR4 expression in an orthotopic model of human hepatocellular carcinoma
dc.typeJournal Article
dcterms.dateSubmitted2013-03-19
dcterms.source.volume8
dcterms.source.number3
dcterms.source.startPage1
dcterms.source.endPage11
dcterms.source.issn19326203
dcterms.source.titlePLoS ONE
curtin.digitool.pid190235
curtin.note

This article is published under the Open Access publishing model and distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0/. Please refer to the licence to obtain terms for any further reuse or distribution of this work.

curtin.pubStatusPublished
curtin.department
curtin.identifier.scriptidPUB-HEA-SBS-JT-72761
curtin.accessStatusOpen access


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