World Library  


Add to Book Shelf
Flag as Inappropriate
Email this Book

Plos One : a Novel Mmp-2 Inhibitor 3-azidowithaferin a 3- Azidowa Abrogates Cancer Cell Invasion and Angiogenesis by Modulating Extracellular Par-4, Volume 7

By Nie, Daotai

Click here to view

Book Id: WPLBN0003932990
Format Type: PDF eBook :
File Size:
Reproduction Date: 2015

Title: Plos One : a Novel Mmp-2 Inhibitor 3-azidowithaferin a 3- Azidowa Abrogates Cancer Cell Invasion and Angiogenesis by Modulating Extracellular Par-4, Volume 7  
Author: Nie, Daotai
Volume: Volume 7
Language: English
Subject: Journals, Science, Medical Science
Collections: Periodicals: Journal and Magazine Collection (Contemporary)
Historic
Publication Date:
Publisher: Plos

Description
Description : Background : Withaferin A, which is a naturally derived steroidal lactone, has been found to prevent angiogenesis and metastasis in diverse tumor models. It has also been recognized by different groups for prominent anti-carcinogenic roles. However, in spite of these studies on withanolides, their detailed anti-metastatic mechanism of action remained unknown. The current study has poised to address the machinery involved in invasion regulation by stable derivative of Withaferin A, 3-azido Withaferin A (3-azidoWA) in human cervical HeLa and prostate PC-3 cells. Methods and Principal Findings : Sub-toxic concentration of 3-azidowithaferin A (3-azido WA) inhibited cancer cell motility and invasion in wound healing and Boyden chamber invasion by suppressing MMP-2 activity in gelatin zymography and its expression has proved to be a major obstacle in chemo-sensitivity. We have uncovered a novel mechanism of 3-azidoWA induced extracellular pro-apoptotic candidate tumor suppressor Par-4 protein stimulation in conditioned media and also noticed a concomitant marked reduction in pAkt and pERK signaling by immunoblot analysis. Furthermore, our zymography results suggest 3-azidoWA induced MMP-2 inhibition was mediated through secretory Par-4. The inhibition of apoptosis by 3-azidoWA could not restore MMP-2 gelatinase activity. In addition to this, our in vivo animal experiments data showed 3-azidoWA abrogated neovascularisation in dose dependent manner in mouse Matrigel plug assay. Conclusion/Significance : For this report, we found that 3-azidoWA suppressed motility and invasion of HeLa and PC-3 cells in MMP-2 dependent manner. Our in vitro result strongly suggests that sub-toxic doses of 3-azidoWA enhanced the secretion of extracellular Par-4 that abolished secretory MMP-2 expression and activity. Depletion of secretory Par-4 restored MMP-2 expression and invasion capability of HeLa and PC-3 cells. Further, our findings implied that 3-azidoWA attenuated internal phospho-ERK and phospho-Akt expression in a dose dependent manner might play a key role in inhibition of mouse angiogenesis by 3-azidoWA.

 

Click To View

Additional Books


  • Plos One : Mhc Class II Tetramers Made f... (by )
  • Plos One : Evaluation of Multiple-locus ... (by )
  • Plos One : Comparative Transcriptomic An... (by )
  • Plos One : Chemotherapeutic Potential of... (by )
  • Plos One : Gliadin Fragments and a Speci... (by )
  • Plos One : Joint Effect of Genetic and L... (by )
  • Plos One : Amelioration of Behavioral Ab... (by )
  • Plos One : Multivariate Analyses of Amyl... (by )
  • Plos One : Cops ; a Sensitive and Accura... (by )
  • Plos One : Random Effects Models and Mul... (by )
  • Plos One : N-acetylglucosamine Kinase, H... (by )
  • Plos One : Rad001 Enhances the Potency o... (by )
Scroll Left
Scroll Right

 



Copyright © World Library Foundation. All rights reserved. eBooks from World Library are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.