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Author Correction: Novel Indole-fused benzo-oxazepines (IFBOs) inhibit invasion of hepatocellular carcinoma by targeting IL-6 mediated JAK2/STAT3 oncogenic signals

Authors :
Biswanath Maity
Amit Rai
Sudipta Saha
Archana S. Bhadauria
Anand Prakash
Pranesh Kumar
Sneha Nath
Vinit Raj
Dinesh Kumar
Umesh Kumar
Amit K Keshari
Ashok K. Singh
Source :
Scientific Reports, Scientific Reports, Vol 10, Iss 1, Pp 1-2 (2020)
Publication Year :
2020
Publisher :
Springer Science and Business Media LLC, 2020.

Abstract

Inspired by the well-documented tumor protecting ability of paullones, recently, we synthesized novel paullone-like scaffolds, indole-fused benzo-oxazepines (IFBOs), and screened them against hepatocellular carcinoma (HCC) specific Hep-G2 cells. Three of the synthesized compounds significantly attenuated the progression of HCC in vitro. By computational studies, we further discovered that IFBOs exhibited a stable binding complex with the IL-6 receptor. In this context, we investigated in vivo study using the nitrosodiethyl amine (NDEA)-induced HCC model, which strengthened our previous findings by showing the blockade of the IL-6 mediated JAK2/STAT3 oncogenic signaling pathway. Treatment with IFBOs showed remarkable attenuation of cellular proliferation, as evidenced through a decrease in the number of nodules, restoration of body weight, oxidative stress parameters, liver marker enzymes and histological architecture. Interestingly, using a metabolomic approach we further discovered that IFBOs can restore the perturbed metabolic profile associated with the HCC condition to normalcy. Particularly, the efficacy of compound 6a for an anti-HCC response was significantly better than the marketed chemotherapeutic drug, 5-fluorouracil. Altogether, these remarkable findings open up possibilities of developing IFBOs as novel future candidate molecules for plausible alternatives for HCC treatment.

Details

ISSN :
20452322
Volume :
10
Database :
OpenAIRE
Journal :
Scientific Reports
Accession number :
edsair.doi.dedup.....b2b73d9cbb4c19bdc1cb1eba33543a19
Full Text :
https://doi.org/10.1038/s41598-020-59134-9