Novel 1,3,4-oxadiazole induces anticancer activity by targeting NF-KB in hepatocellular carcinoma cells

Mohan, C. D. and Anilkumar, N. C. and Rangappa, S. and Shanmugam, M. K. and Mishra, S. and Chinnathambi, A. and Alharbi, S. A. and Bhattacharjee, Atanu and Sethi, G. and Kumar, A. P. and Basappa and Rangappa, K. S. (2018) Novel 1,3,4-oxadiazole induces anticancer activity by targeting NF-KB in hepatocellular carcinoma cells. Frontiers in Oncology, 8 (42).

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Aberrant activation of NF-κB is linked with the progression of human malignancies including hepatocellular carcinoma (HCC), and blockade of NF-κB signaling could be a potential target in the treatment of several cancers. Therefore, designing of novel small molecule inhibitors that target NF-κB activation is of prime importance in the treatment of several cancers. In the present work, we report the synthesis of series of 1,3,4-oxadiazoles, investigated their anticancer potential against HCC cells, and identified 2-(3-chlorobenzo[b]thiophen-2-yl)-5-(3-methoxyphenyl)-1,3,4-oxadiazole (CMO) as the lead compound. Further, we examined the effect of CMO on cell cycle distribution (flow cytometry), apoptosis (annexin V-propidium iodide-FITC staining), and phosphorylation of NF-κB signaling pathway proteins (IκB and p65) in HCC cells. We found that CMO induced antiproliferative effect in dose- and time-dependent manner. Also, CMO significantly increased the percentage of sub-G1 cell population and induced apoptosis. Furthermore, CMO found to decrease the phosphorylation of IκB (Ser 32) in the cytoplasmic extract and p65 (Ser 536) in the nuclear extract of HCC cells. It also abrogated the DNA binding ability and transcriptional activity of NF-κB. CMO induced the cleavage of PARP and caspase-3 in a time-dependent manner. In addition, transfection with p65 small interfering RNA blocks CMO-induced caspase-3/7 activation. Molecular docking analysis revealed that CMO interacts with the hydrophobic region of p65 protein. Thus, we are reporting CMO as an inhibitor of NF-κB signaling pathway. © 2018 Mohan, Anilkumar, Rangappa, Shanmugam, Mishra, Chinnathambi, Alharbi, Bhattacharjee, Sethi, Kumar, Basappa and Rangappa.

Item Type: Article
Subjects: B Life Science > Molecular Biology
Divisions: Department of > Molecular Biology
Depositing User: Manjula P Library Assistant
Date Deposited: 07 Jan 2021 08:03
Last Modified: 20 Jun 2022 11:29

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