[Home ] [Archive]   [ فارسی ]  
:: Main :: About :: Current Issue :: Archive :: Search :: Submit :: Contact ::
Main Menu
Home::
Journal Information::
Articles archive::
For Authors::
For Reviewers::
Registration::
Contact us::
Site Facilities::
Indexing & Abstracting::
Publication Ethics::
::
Search in website

Advanced Search
..
Receive site information
Enter your Email in the following box to receive the site news and information.
..
Indexing & Abstracting
DOAJ
GOOGLE SCHOLAR
..
:: Volume 26, Issue 3 (7-2021) ::
__Armaghane Danesh__ 2021, 26(3): 351-370 Back to browse issues page
The Effect of Podophyllotoxin as an Inducer of Apoptosis Using Molecular Docking Method
MS Talebianpoor1 , H Bardania1 , M Mansourian 2
1- Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran
2- Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran , mahboubehmansourian90@gmail.com
Abstract:   (1553 Views)
Background and aim: Podophyllotoxin is used as one of the main treatments for genital warts. It is a precursor of etoposide and teniposide, which is used in the treatment of various cancers. Despite a large number of cancer studies, the exact mechanism of podophyllotoxin remains unknown. Suppression of enzymatic activity of adult caspases occurs in cancer cells in the presence of specific members of the inhibitor of apoptosis proteins (IAPs) family such as X-linked inhibitor of apoptosis protein (XIAP), cellular inhibitor of apoptosis proteins (cIAP1), and Survivin. By specifically binding a second mitochondria-derived activator of caspases-mimetics (Smac-mimetics) to negative apoptosis regulators, inhibition of IAPs-mediated caspases is eliminated and apoptosis is induced. The aim of the present study was used to determine the mechanism of action of podophyllotoxin as an inducer of apoptosis using molecular docking method.
 
Methods: The present bioinformatics study was conducted in 2020. Molecular docking method was used to calculate the molecular interaction of podophyllotoxin with proteins associated with initiator and effector caspases including baculovirus IAP repeat (BIR3) of XIAP / cAIP1 and Survivin, as well as B-cell lymphoma-2 (Bcl-2) and epidermal growth factor receptor (EGFR). The theoretical binding site of podophyllotoxin on these anti-apoptotic proteins was determined as an inhibitor to obtain information on the initial interaction, free binding energy and inhibition constant by molecular docking method. The collected data were analyzed using different software and compared with the results of related articles.
 
Results: The proapoptotic activity of podophyllotoxin as an apoptotic-inducing agent is associated with the signaling pathways of caspases 3, 7, 8, and 9. The key activation mechanisms of these caspases may be due to podophyllotoxin binding and induction of conformational changes at active sites of the XIAP / cAIP1-BIR3 and Survivin located near or at the same Smac-mimetics binding site. Three strong hydrogen bonds with the amino acids Tyr108, Ser117 and Glu118 play important roles in the stabilization of the Bcl-2-podophyllotoxin complex. Podophyllotoxin, similar to EGFR inhibitors, forms several hydrophobic interactions and two strong hydrogen bonds with Thr830 and Met769 with a bond-free energy of -7.85 kcal / mol and an inhibition constant of Ki = 1.76 µM.
 
Conclusion: Induction of apoptosis in cancer cells by podophyllotoxin can be attributed to several different mechanisms. Predicted binding conformations showed that podophyllotoxin had valuable inhibitory potential. Therefore, podophyllotoxin may be considered as an effective anticancer agent for further research into drug development.
Keywords:    Podophyllotoxin, Cancer, Apoptosis, Molecular docking 
Full-Text [PDF 1056 kb]   (590 Downloads)    
Type of Study: Research | Subject: Special
Received: 2021/02/11 | Accepted: 2021/05/11 | Published: 2021/07/6
Send email to the article author

Add your comments about this article
Your username or Email:

CAPTCHA



XML   Persian Abstract   Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Talebianpoor M, Bardania H, Mansourian M. The Effect of Podophyllotoxin as an Inducer of Apoptosis Using Molecular Docking Method. armaghanj 2021; 26 (3) :351-370
URL: http://armaghanj.yums.ac.ir/article-1-3032-en.html


Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Volume 26, Issue 3 (7-2021) Back to browse issues page
ارمغان دانش Armaghane Danesh
Persian site map - English site map - Created in 0.05 seconds with 39 queries by YEKTAWEB 4645