Please use this identifier to cite or link to this item:
https://doi.org/10.18632/oncotarget.14606
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dc.title | A novel benzimidazole derivative, MBIC inhibits tumor growth and promotes apoptosis via activation of ROS-dependent JNK signaling pathway in hepatocellular carcinoma | |
dc.contributor.author | Dai X. | |
dc.contributor.author | Wang L. | |
dc.contributor.author | Deivasigamni A. | |
dc.contributor.author | Looi C.Y. | |
dc.contributor.author | Karthikeyan C. | |
dc.contributor.author | Trivedi P. | |
dc.contributor.author | Chinnathambi A. | |
dc.contributor.author | Alharbi S.A. | |
dc.contributor.author | Arfuso F. | |
dc.contributor.author | Dharmarajan A. | |
dc.contributor.author | Goh B.C. | |
dc.contributor.author | Hui K.M. | |
dc.contributor.author | Kumar A.P. | |
dc.contributor.author | Mustafa M.R. | |
dc.contributor.author | Sethi G. | |
dc.date.accessioned | 2020-09-01T00:59:03Z | |
dc.date.available | 2020-09-01T00:59:03Z | |
dc.date.issued | 2017 | |
dc.identifier.citation | Dai 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.issn | 19492553 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/173807 | |
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.source | Unpaywall 20200831 | |
dc.subject | acetylcysteine | |
dc.subject | benzimidazole derivative | |
dc.subject | caspase 3 | |
dc.subject | methyl 2 (5 fluoro 2 hydroxyphenyl) 1h benzo[d]imidazole 5 carboxylate | |
dc.subject | reactive oxygen metabolite | |
dc.subject | stress activated protein kinase | |
dc.subject | unclassified drug | |
dc.subject | animal experiment | |
dc.subject | animal model | |
dc.subject | animal tissue | |
dc.subject | antineoplastic activity | |
dc.subject | apoptosis | |
dc.subject | Article | |
dc.subject | cancer inhibition | |
dc.subject | cell invasion | |
dc.subject | cell migration | |
dc.subject | cell viability | |
dc.subject | controlled study | |
dc.subject | female | |
dc.subject | flow cytometry | |
dc.subject | human | |
dc.subject | human cell | |
dc.subject | liver cell carcinoma | |
dc.subject | mitochondrion | |
dc.subject | mouse | |
dc.subject | nonhuman | |
dc.subject | signal transduction | |
dc.subject | Western blotting | |
dc.type | Article | |
dc.contributor.department | DEPT OF PHARMACY | |
dc.contributor.department | DEPT OF PHARMACOLOGY | |
dc.contributor.department | DUKE-NUS MEDICAL SCHOOL | |
dc.contributor.department | CANCER SCIENCE INSTITUTE OF SINGAPORE | |
dc.description.doi | 10.18632/oncotarget.14606 | |
dc.description.sourcetitle | Oncotarget | |
dc.description.volume | 8 | |
dc.description.issue | 8 | |
dc.description.page | 12831-12842 | |
Appears in Collections: | Staff Publications Elements |
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