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Correction: Novel Synthetic Oxazines Target NF-κB in Colon Cancer In Vitro and Inflammatory Bowel Disease In Vivo

Authors :
Anilkumar C. Nirvanappa
Chakrabhavi Dhananjaya Mohan
Shobith Rangappa
Hanumappa Ananda
Alexey Yu Sukhorukov
Muthu K. Shanmugam
Mahalingam S. Sundaram
Siddaiah Chandra Nayaka
Kesturu S. Girish
Arunachalam Chinnathambi
M. E. Zayed
Sulaiman Ali Alharbi
Gautam Sethi
null Basappa
Kanchugarakoppal S. Rangappa
Source :
PLoS ONE, Vol 12, Iss 4, p e0175659 (2017), PLoS ONE
Publication Year :
2017
Publisher :
Public Library of Science (PLoS), 2017.

Abstract

Aberrant activation of nuclear factor kappa B (NF-κB) has been linked with the pathogenesis of several proinflammatory diseases including number of cancers and inflammatory bowel diseases. In the present work, we evaluated the anticancer activity of 1,2-oxazines derivatives against colorectal cancer cell lines and identified 2-((2-acetyl-6,6-dimethyl-4-phenyl-5,6-dihydro-2H-1,2-oxazin-3-yl)methyl)isoindoline-1,3-dione (API) as the lead anticancer agent among the tested compounds. The apoptosis inducing effect of API was demonstrated using flow cytometry analysis and measuring the caspase 3/7 activity in API treated cells. Based on the literature on inhibition of NF-κB by oxazines, we evaluated the effect of 1,2-oxazines against the ability of NF-κB binding to DNA, NF-κB-dependent luciferase expression and IκBα phosphorylation. We found that, API abrogate constitutive activation of NF-κB and inhibits IκBα phosphorylation in HCT116 cells. Our in silico analysis revealed the binding of oxazines to the hydrophobic cavity that present between the interface of p65 and IκBα. Given the relevance with aberrant activation of NF-κB in inflammation bowel disease (IBD), we evaluated the effect of API on dextran sulphate sodium-induced IBD mice model. The treatment of IBD induced mice with API decreased the myeloperoxidase activity in colonic extract, modulated the colon length and serum levels of pro- and anti-inflammatory cytokines such as TNF-α, IFN-γ, IL-6, IL-1β and IL-10. Furthermore, the histological analysis revealed the restoration of the distorted cryptic epithelial structure of colon in the API treated animals. In conclusion, we comprehensively validated the NF-κB inhibitory efficacy of API that targets NF-κB in in vitro colon cancer and an in vivo inflammatory bowel disease model.

Details

Language :
English
ISSN :
19326203
Volume :
12
Issue :
4
Database :
OpenAIRE
Journal :
PLoS ONE
Accession number :
edsair.doi.dedup.....39922d5a334191cec9de806be09c01cf