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Molecular mechanism of interaction of mitocurcumin-1 with Akt1 and STAT3: An <i>In silico</i> approach

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Title Molecular mechanism of interaction of mitocurcumin-1 with Akt1 and STAT3: An In silico approach
 
Creator Vasagiri, Nagarjuna
Kutala, Vijay Kumar
 
Subject Molecular modeling
Curcumin
Mitocurcumin-1
Apoptosis
Cancer cells
Akt1
STAT3
 
Description 308-313
The bioavailability of curcumin is the
limiting factor for its effective use in anti-cancer therapy. Recently, we
reported a novel approach to enhance the
cellular uptake by conjugating curcumin with triphenyl phosphonium, named
mitocurcumin-1. We found that such conjugation significantly increased
the uptake of curcumin in various cancer cells and caused cancer cell death by
inducing apoptosis by decreasing the phosphorylation of Akt1 (Thr308) and STAT3
(Tyr705). In this study, a molecular mechanistic model deciphering the
regulation of phosphorylation of Akt1 and STAT3 by mitocurcumin-1 was
investigated and compared with curcumin. The protein structures were obtained
from protein data bank data base and protein-ligand interaction studies were
performed with mitocurcumin-1 and curcumin. Docking interaction studies of
mitocurcumin-1 with Akt1 and STAT3 active sites showed a strong binding
affinity of -60.4107 Kcal/mol and
-51.1734 Kcal/mol respectively, suggesting mitocurcumin-1 interacted with the
residues at the active sites of phosphorylation of these molecules. Further, a Chi
rotationary root mean square deviation of 1.468 Å and 3.965 Å at the active
sites in Akt1 and STAT3, respectively indicated that changes in the
conformation of protein structure at the active site resulted in the inhibition
of phosphorylation of these molecules. To conclude, by using molecular modeling
approaches for the first time, we demonstrated the inhibition of Akt1 and STAT3
phosphorylation by mitocurcumin-1.
 
Date 2014-09-03T04:21:00Z
2014-09-03T04:21:00Z
2014-08
 
Type Article
 
Identifier 0975-0959 (Online); 0301-1208 (Print)
http://hdl.handle.net/123456789/29325
 
Language en_US
 
Rights CC Attribution-Noncommercial-No Derivative Works 2.5 India
 
Publisher NISCAIR-CSIR, India
 
Source IJBB Vol.51(4) [August 2014]