title: Dietary phytochemicals as potent chemotherapeutic agents against breast cancer: Inhibition of NF-κB pathway via molecular interactions in rel homology domain of its precursor protein p105.
abstract: BACKGROUND
  Dietary phytochemicals consist of a wide variety of biologically active compounds that are ubiquitous in plants, many of which have been reported to have anti-tumor as well as anti-inflammatory properties.
  
  
  OBJECTIVE
  In the present study, we aimed to validate these findings by using docking protocols and explicate the possible mechanism of action for a dataset of nine phytochemicals namely boswellic acid, 1-caffeoylquinic acid, ellagic acid, emodin, genistein, guggulsterone, quercetin, resveratrol, and sylibinin from different plants against the nuclear factor- kappaB (NF-κB) precursor protein p105, an important transcription factor reported to be overexpressed in breast cancer.
  
  
  METHODS
  2-D structures of all phytochemicals were retrieved from PubChem Compound database and their subsequent conversion into 3-D structures was performed by using online software system CORINA. The X-ray crystallographic structure of the NF-κB precursor p105 was extracted from Brookhaven Protein Data Bank. Molecular docking simulation study was carried out by using AutoDock Tools 4.0.
  
  
  RESULTS
  Our results showed significant binding affinity of different phytochemicals with the Rel homology domain of the NF-κB precursor protein p105. Quercetin and 1-caffeoylquinic acid were found to be very effective inhibitors against target molecule as they showed binding energy of -12.11 and -11.50 Kcal/mol, respectively. The order of affinity of other ligands with p105 was found as follows: guggulsterone > sylibinin > emodin > resveratrol > genistein > boswellic acid > ellagic acid.
  
  
  CONCLUSIONS
  Our in silico study has explored the possible chemopreventive mechanism of these phytochemicals against the NF-κB precursor protein p105 and deciphered that quercetin, 1-caffeoylquinic acid and guggulsterone were the potent inhibitors against target molecule. In addition, large scale preclinical and clinical trials are needed to explore the role of these chemotherapeutic molecules against the NF-κB precursor protein p105 in cure and prevention of breast cancer.
authors: Department of Biotechnology, Microbiology and Bioinformatics, Integral University, Lucknow, Uttar Pradesh, India.
authors: Mohammad K A
authors: MK
authors: Khan
authors: Irfan A
authors: IA
authors: Ansari
authors: M Salman
authors: MS
authors: Khan
authors: Jamal M
authors: JM
authors: Arif
keywords: 1-Caffeoylquinic acid; NF-κB; boswellic acid; breast cancer; emodin; guggulsterone; molecular docking; rel homology domain; sylibinin
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