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Open AccessArticle

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

1
Division of Life Sciences, Division of Applied Life Science (BK21 Plus), Plant Molecular Biology and Biotechnology Research Center (PMBBRC), Research Institute of Natural Science (RINS), Gyeongsang National University (GNU), 501 Jinju-daero, Jinju 52828, Korea
2
Research Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, 501 Jinju-daero, Jinju 52828, Korea
3
Department of Chemistry (BK 21 plus), Research Institute of Natural Science (RINS), Gyeongsang National University, Jinju, Gyeongnam 52828, Korea
*
Author to whom correspondence should be addressed.
Equal contribution.
Biomolecules 2020, 10(6), 857; https://doi.org/10.3390/biom10060857
Received: 31 March 2020 / Revised: 15 May 2020 / Accepted: 20 May 2020 / Published: 4 June 2020
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 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. View Full-Text
Keywords: DDX3; cancers; natural compounds; combinatorial treatment DDX3; cancers; natural compounds; combinatorial treatment
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MDPI and ACS Style

Rampogu, S.; Kim, S.M.; Son, M.; Baek, A.; Park, C.; Lee, G.; Kim, Y.; Kim, G.S.; Kim, J.H.; Lee, K.W. A Computational Approach with Biological Evaluation: Combinatorial Treatment of Curcumin and Exemestane Synergistically Regulates DDX3 Expression in Cancer Cell Lines. Biomolecules 2020, 10, 857. https://doi.org/10.3390/biom10060857

AMA Style

Rampogu S, Kim SM, Son M, Baek A, Park C, Lee G, Kim Y, Kim GS, Kim JH, Lee KW. A Computational Approach with Biological Evaluation: Combinatorial Treatment of Curcumin and Exemestane Synergistically Regulates DDX3 Expression in Cancer Cell Lines. Biomolecules. 2020; 10(6):857. https://doi.org/10.3390/biom10060857

Chicago/Turabian Style

Rampogu, Shailima; Kim, Seong M.; Son, Minky; Baek, Ayoung; Park, Chanin; Lee, Gihwan; Kim, Yumi; Kim, Gon S.; Kim, Ju H.; Lee, Keun W. 2020. "A Computational Approach with Biological Evaluation: Combinatorial Treatment of Curcumin and Exemestane Synergistically Regulates DDX3 Expression in Cancer Cell Lines" Biomolecules 10, no. 6: 857. https://doi.org/10.3390/biom10060857

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