Detailed Information

Cited 16 time in webofscience Cited 15 time in scopus
Metadata Downloads

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

Authors
Rampogu, ShailimaKim, Seong MinSon, MinkyBaek, AyoungPark, ChaninLee, GihwanKim, YumiKim, Gon SupKim, Ju HyunLee, Keun Woo
Issue Date
Jun-2020
Publisher
MDPI
Keywords
DDX3; cancers; natural compounds; combinatorial treatment
Citation
BIOMOLECULES, v.10, no.6
Indexed
SCIE
SCOPUS
Journal Title
BIOMOLECULES
Volume
10
Number
6
URI
https://scholarworks.gnu.ac.kr/handle/sw.gnu/6561
DOI
10.3390/biom10060857
ISSN
2218-273X
2218-273X
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 mu M) and exemestane (50 mu M) a synergism was exhibited, strikingly downregulating the DDX3 expression and has enhanced apoptosis in three cell lines. The obtained results illuminate the use of curcumin as an alternative DDX3 inhibitor and can serve as a chemical scaffold to design new small molecules.
Files in This Item
There are no files associated with this item.
Appears in
Collections
자연과학대학 > 화학과 > Journal Articles
수의과대학 > Department of Veterinary Medicine > Journal Articles

qrcode

Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.

Related Researcher

Researcher Kim, Gon Sup photo

Kim, Gon Sup
수의과대학 (수의학과)
Read more

Altmetrics

Total Views & Downloads

BROWSE