Document Detail


YC-1 targeting of hypoxia-inducible factor-1α reduces RGC-5 cell viability and inhibits cell proliferation.
MedLine Citation:
PMID:  22736948     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: The survival of retinal ganglion cells (RGCs) is a hallmark of many optic neurodegenerative diseases such as glaucoma. YC-1, a potential anticancer drug, is known to be able to decrease the stability and protein expression of hypoxia-inducible factor (HIF)-1α that is triggered by hypoxia and related to RGC survival. We hypothesized that YC-1 may alter RGC cell viability through the down-regulation of HIF-1α.
METHODS: Cell viability of the RGC-5 cell line was measured with a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Flow cytometry, a LIVE/DEAD viability assay, and high-content screening (HCS) with MKI67 (K(i)-67) monoclonal antibodies were used to detect cell death and cellular proliferation.
RESULTS: We found that cells treated with 20 µM YC-1 for 24 h decreased the HIF-1α level in an RGC-5 cell line using immunoblotting and reduced the live cell number in an MTT assay. Results of flow cytometry and HCS demonstrated that reducing the cell proliferation of RGC-5 cells, not cell death, led to the decreased level in the MTT assay.
CONCLUSIONS: Our findings demonstrate that YC-1-induced down-regulation of HIF-1α might reduce RGC cell proliferation and viability under normoxia, which implies a role of YC-1 in the neuroprotective effect for further clinical applications.
Authors:
Leo Tsui; Tsorng-Harn Fong; I-Jong Wang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-06-15
Journal Detail:
Title:  Molecular vision     Volume:  18     ISSN:  1090-0535     ISO Abbreviation:  Mol. Vis.     Publication Date:  2012  
Date Detail:
Created Date:  2012-06-27     Completed Date:  2012-11-13     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  9605351     Medline TA:  Mol Vis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1594-603     Citation Subset:  IM    
Affiliation:
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
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MeSH Terms
Descriptor/Qualifier:
Antibodies / pharmacology
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Cell Line
Cell Proliferation / drug effects
Cell Survival / drug effects
Dose-Response Relationship, Drug
Down-Regulation / drug effects*,  genetics
Humans
Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors*,  genetics
Indazoles / pharmacology*
Ki-67 Antigen / metabolism
RNA, Messenger / biosynthesis
Retinal Ganglion Cells / cytology,  drug effects*,  metabolism
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / drug effects
Chemical
Reg. No./Substance:
0/Antibodies; 0/Antineoplastic Agents; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/Indazoles; 0/Ki-67 Antigen; 0/RNA, Messenger; 154453-18-6/3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole
Comments/Corrections

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


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