A Computational Approach with Biological Evaluation: Combinatorial Treatment of Curcumin and Exemestane Synergistically Regulates DDX3 Expression in Cancer Cell Lines.

Biomolecules
Shailima RampoguKeun Woo Lee

Abstract

DDX3 belongs to RNA helicase family that demonstrates oncogenic properties and has gained wider attention due to its role in cancer progression, proliferation and transformation. Mounting reports have evidenced the role of DDX3 in cancers making it a promising target to abrogate DDX3 triggered cancers. Dual pharmacophore models were generated and were subsequently validated. They were used as 3D queries to screen the InterBioScreen database, resulting in the selection of curcumin that was escalated to molecular dynamics simulation studies. In vitro anti-cancer analysis was conducted on three cell lines such as MCF-7, MDA-MB-231 and HeLa, which were evaluated along with exemestane. Curcumin was docked into the active site of the protein target (PDB code 2I4I) to estimate the binding affinity. The compound has interacted with two key residues and has displayed stable molecular dynamics simulation results. In vitro analysis has demonstrated that both the candidate compounds have reduced the expression of DDX3 in three cell lines. However, upon combinatorial treatment of curcumin (10 and 20 μM) and exemestane (50 μM) a synergism was exhibited, strikingly downregulating the DDX3 expression and has enhanced apoptosis in three cell li...Continue Reading

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Citations

May 28, 2021·Frontiers in Chemistry·Shailima Rampogu, Keun Woo Lee
Jun 28, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Shailima RampoguKeun Woo Lee

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Methods Mentioned

BETA
InterBioScreen
MDS
protein assay
electrophoresis
Feature Mapping

Software Mentioned

UCSF Chimera
MDS
Ligand Pharmacophore Mapping
GraphPad
GraphPad Prism
Image J
GROMACS
CHARMm
CDOCKER
visual dynamics ( VMD )

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