Please use this identifier to cite or link to this item: https://doi.org/10.18632/oncotarget.14606
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dc.titleA novel benzimidazole derivative, MBIC inhibits tumor growth and promotes apoptosis via activation of ROS-dependent JNK signaling pathway in hepatocellular carcinoma
dc.contributor.authorDai X.
dc.contributor.authorWang L.
dc.contributor.authorDeivasigamni A.
dc.contributor.authorLooi C.Y.
dc.contributor.authorKarthikeyan C.
dc.contributor.authorTrivedi P.
dc.contributor.authorChinnathambi A.
dc.contributor.authorAlharbi S.A.
dc.contributor.authorArfuso F.
dc.contributor.authorDharmarajan A.
dc.contributor.authorGoh B.C.
dc.contributor.authorHui K.M.
dc.contributor.authorKumar A.P.
dc.contributor.authorMustafa M.R.
dc.contributor.authorSethi G.
dc.date.accessioned2020-09-01T00:59:03Z
dc.date.available2020-09-01T00:59:03Z
dc.date.issued2017
dc.identifier.citationDai X., Wang L., Deivasigamni A., Looi C.Y., Karthikeyan C., Trivedi P., Chinnathambi A., Alharbi S.A., Arfuso F., Dharmarajan A., Goh B.C., Hui K.M., Kumar A.P., Mustafa M.R., Sethi G. (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) : 12831-12842. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.14606
dc.identifier.issn19492553
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/173807
dc.description.abstractA 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.sourceUnpaywall 20200831
dc.subjectacetylcysteine
dc.subjectbenzimidazole derivative
dc.subjectcaspase 3
dc.subjectmethyl 2 (5 fluoro 2 hydroxyphenyl) 1h benzo[d]imidazole 5 carboxylate
dc.subjectreactive oxygen metabolite
dc.subjectstress activated protein kinase
dc.subjectunclassified drug
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectantineoplastic activity
dc.subjectapoptosis
dc.subjectArticle
dc.subjectcancer inhibition
dc.subjectcell invasion
dc.subjectcell migration
dc.subjectcell viability
dc.subjectcontrolled study
dc.subjectfemale
dc.subjectflow cytometry
dc.subjecthuman
dc.subjecthuman cell
dc.subjectliver cell carcinoma
dc.subjectmitochondrion
dc.subjectmouse
dc.subjectnonhuman
dc.subjectsignal transduction
dc.subjectWestern blotting
dc.typeArticle
dc.contributor.departmentDEPT OF PHARMACY
dc.contributor.departmentDEPT OF PHARMACOLOGY
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.description.doi10.18632/oncotarget.14606
dc.description.sourcetitleOncotarget
dc.description.volume8
dc.description.issue8
dc.description.page12831-12842
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