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dc.contributor.authorDai, X.
dc.contributor.authorWang, L.
dc.contributor.authorDeivasigamni, A.
dc.contributor.authorLooi, C.
dc.contributor.authorKarthikeyan, C.
dc.contributor.authorTrivedi, P.
dc.contributor.authorChinnathambi, A.
dc.contributor.authorAlharbi, S.
dc.contributor.authorArfuso, Frank
dc.contributor.authorDharmarajan, Arunasalam
dc.contributor.authorGoh, B.
dc.contributor.authorHui, K.
dc.contributor.authorKumar, Alan Prem
dc.contributor.authorMustafa, M.
dc.contributor.authorSethi, Gautam
dc.date.accessioned2017-03-15T22:24:02Z
dc.date.available2017-03-15T22:24:02Z
dc.date.created2017-03-08T06:39:37Z
dc.date.issued2017
dc.identifier.citationDai, X. and Wang, L. and Deivasigamni, A. and Looi, C. and Karthikeyan, C. and Trivedi, P. and Chinnathambi, A. et al. 2017. A novel benzimidazole derivative, MBIC inhibits tumor growth and promotes apoptosis via activation of ROS-dependent JNK signaling pathway in hepatocellular carcinoma. Oncotarget. 8 (8): pp. 12831-12842.
dc.identifier.urihttp://hdl.handle.net/20.500.11937/50403
dc.identifier.doi10.18632/oncotarget.14606
dc.description.abstract

A prior screening programme carried out using MTT assay by our group identified a series of novel benzimidazole derivatives, among which Methyl 2-(5-fluoro-2- hydroxyphenyl)-1H- benzo[d]imidazole-5-carboxylate (MBIC) showed highest anticancer efficacy compared to that of chemotherapeutic agent, cisplatin. In the present study, we found that MBIC inhibited cell viability in different hepatocellular carcinoma (HCC) cell lines without exerting significant cytotoxic effects on normal liver cells. Annexin V-FITC/PI flow cytometry analysis and Western blotting results indicated that MBIC can induce apoptosis in HCC cells, which was found to be mediated through mitochondria associated proteins ultimately leading to the activation of caspase-3. The exposure to MBIC also resulted in remarkable impairment of HCC cell migration and invasion. In addition, treatment with MBIC led to a rapid generation of reactive oxygen species (ROS) and substantial activation of c-Jun-N-terminal kinase (JNK). The depletion of ROS by N-Acetyl cysteine (NAC) partially blocked MBIC-induced apoptosis and JNK activation in HCC cells. Finally, MBIC significantly inhibited tumor growth at a dose of 25 mg/kg in an orthotopic HCC mouse model. Taken together, these results demonstrate that MBIC may inhibit cell proliferation via ROS-mediated activation of the JNK signaling cascade in HCC cells.

dc.publisherImpact Journals LLC
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/
dc.titleA novel benzimidazole derivative, MBIC inhibits tumor growth and promotes apoptosis via activation of ROS-dependent JNK signaling pathway in hepatocellular carcinoma
dc.typeJournal Article
dcterms.source.volume8
dcterms.source.number8
dcterms.source.startPage12831
dcterms.source.endPage12842
dcterms.source.issn1949-2553
dcterms.source.titleOncotarget
curtin.departmentSchool of Biomedical Sciences
curtin.accessStatusOpen access


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