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Nitric Oxide induces Cancer Stem Cell-like Phenotypes in Human Lung Cancer Cells.
MedLine Citation:
PMID:  25411331     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Even though tremendous advances have been made in the treatment of cancers during the past decades, success rate among cancer patients is still dismal largely due to problems associated with chemo/radio-resistance and relapse. Emerging evidence has indicated that cancer stem cells (CSCs) are behind the resistance and recurrence problems, but our understanding of their regulation is limited. Rapid reversible changes of CSC-like cells within tumors may result from the effect of biological mediators found in tumor microenvironment. Here we show how nitric oxide (NO), a key cellular modulator whose level is elevated in many tumors, affects CSC-like phenotypes of human non-small-cell lung carcinoma (NSCLC) H292 and H460 cells. Exposure of NO gradually altered the cell morphology towards mesenchymal stem-like shape. NO exposure promoted CSC-like phenotype indicated by increased expression of known CSC markers, CD133 and ALDH1A1, in the exposed cells. This effect of NO on stemness was reversible after cessation of the NO treatment for 7 days. Furthermore, such effect was reproducible using another NO-donor, S-nitroso-N-acetylpenicillamine (SNAP). Importantly, inhibition of NO by known NO scavenger 2-(4-carboxy-phenyl)-4,4,5,5 tetramethylimidazoline-1-oxy-3-oxide (PTIO) strongly inhibited CSC-like aggressive cellular behavior and marker expression. Lastly, we unveiled the underlying mechanism of NO action through the activation of caveolin-1 (Cav-1) which is upregulated by NO and is responsible for the aggressive behavior of the cells, including anoikis resistance, anchorage-independent cell growth, and increased cell migration and invasion. These findings indicate a novel role of NO in CSC regulation and its importance in aggressive cancer behaviors through Cav-1 upregulation.
Authors:
Nuttida Yongsanguanchai; Varisa Pongrakhananon; Apiwat Mutirangura; Yon Rojanasakul; Pithi Chanvorachote
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-11-19
Journal Detail:
Title:  American journal of physiology. Cell physiology     Volume:  -     ISSN:  1522-1563     ISO Abbreviation:  Am. J. Physiol., Cell Physiol.     Publication Date:  2014 Nov 
Date Detail:
Created Date:  2014-11-20     Completed Date:  -     Revised Date:  2014-11-21    
Medline Journal Info:
Nlm Unique ID:  100901225     Medline TA:  Am J Physiol Cell Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  ajpcell.00187.2014     Citation Subset:  -    
Copyright Information:
Copyright © 2014, American Journal of Physiology - Cell Physiology.
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