Document Detail


D-4F, an apoA-I mimetic peptide, inhibits proliferation and tumorigenicity of epithelial ovarian cancer cells by upregulating the antioxidant enzyme MnSOD.
MedLine Citation:
PMID:  21425255     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We recently reported that apoA-I and apoA-I mimetic peptides prevent the development of flank tumors in immunocompetent C57BL/6J mice. To delineate the mechanism(s) of action of apoA-I mimetic peptides in tumor development, we examined the effect of D-4F (an apoA-I mimetic peptide) on the antioxidant status and on the gene expression and function of antioxidant enzymes in ID8 cells (a mouse epithelial ovarian cancer cell line) and in a mouse model. We demonstrate that D-4F treatment significantly reduces the viability and proliferation of ID8 cells, with a concomitant improvement of the antioxidant status of ID8 cells as measured by lipid peroxidation, protein carbonyl, superoxide anion, and hydrogen peroxide levels. D-4F treatment induces MnSOD (but not CuZnSOD) mRNA, protein, and activity. Inhibition of MnSOD in ID8 cells using shRNA vectors abrogates the inhibitory effects of D-4F on ID8 cell viability and proliferation. Moreover, tumor development from ID8 cells carrying shRNA for MnSOD were unaffected by D-4F treatment. Our results suggest that the inhibitory effects of D-4F on ID8 cell proliferation and tumor development are mediated, at least in part, by the induced expression and activity of MnSOD.
Authors:
Ekambaram Ganapathy; Feng Su; David Meriwether; Asokan Devarajan; Victor Grijalva; Feng Gao; Arnab Chattopadhyay; G M Anantharamaiah; Mohamad Navab; Alan M Fogelman; Srinivasa T Reddy; Robin Farias-Eisner
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-05-26
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  130     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2011-12-22     Completed Date:  2012-02-10     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1071-81     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 UICC.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antioxidants / pharmacology*
Apolipoprotein A-I / pharmacology*
Cell Proliferation / drug effects*
Cell Survival / drug effects
Cell Transformation, Neoplastic / drug effects*
Female
Humans
Mice
Neoplasms, Glandular and Epithelial / pathology*
Ovarian Neoplasms / pathology*
Oxidative Stress / drug effects,  physiology
Superoxide Dismutase / metabolism*
Up-Regulation
Grant Support
ID/Acronym/Agency:
HL-082823/HL/NHLBI NIH HHS; HL-30568/HL/NHLBI NIH HHS; P01 HL030568/HL/NHLBI NIH HHS; P01 HL030568-29/HL/NHLBI NIH HHS; R01 HL082823/HL/NHLBI NIH HHS; R01 HL082823-05/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Apolipoprotein A-I; 0/D-4F peptide; EC 1.15.1.1/Superoxide Dismutase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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