Document Detail

The mechanisms of nadroparin-mediated inhibition of proliferation of two human lung cancer cell lines.
MedLine Citation:
PMID:  23106301     Owner:  NLM     Status:  In-Data-Review    
OBJECTIVES: Clinical data suggest that heparin treatment improves survival of lung cancer patients, but the mechanisms involved are not fully understood. We investigated whether low molecular weight heparin nadroparin, directly affects lung cancer cell population growth in conventionally cultured cell lines.
MATERIALS AND METHODS: A549 and CALU1 cells' viability was assessed by MTT and trypan blue exclusion assays. Cell proliferation was assessed using 5-bromo-2-deoxyuridine incorporation. Apoptosis and cell-cycle distribution were analysed by flow cytometry; cyclin B1, Cdk1, p-Cdk1 Cdc25C, p-Cdc25C and p21 expressions were analysed by western blotting. mRNA levels were analysed by real time RT-PCR.
RESULTS: Nadroparin inhibited cell proliferation by 30% in both cell lines; it affected the cell cycle in A549, but not in CALU-1 cells, inducing arrest in the G(2) /M phase. Nadroparin in A549 culture inhibited cyclin B1, Cdk1, Cdc25C and p-Cdc25C, while levels of p-Cdk1 were elevated; p21 expression was not altered. Dalteparin caused a similar reduction in A549 cell population growth; however, it did not alter cyclin B1 expression as expected, based on previous reports. Fondaparinux caused minimal inhibition of A549 cell population growth and no effect on either cell cycle or cyclin B1 expression.
CONCLUSIONS: Nadroparin inhibited proliferation of A549 cells by inducing G(2) /M phase cell-cycle arrest that was dependent on the Cdc25C pathway, whereas CALU-1 cell proliferation was halted by as yet not elucidated modes.
Y Carmazzi; M Iorio; C Armani; S Cianchetti; F Raggi; T Neri; C Cordazzo; S Petrini; R Vanacore; F Bogazzi; P Paggiaro; A Celi
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cell proliferation     Volume:  45     ISSN:  1365-2184     ISO Abbreviation:  Cell Prolif.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-10-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9105195     Medline TA:  Cell Prolif     Country:  England    
Other Details:
Languages:  eng     Pagination:  545-56     Citation Subset:  IM    
Copyright Information:
© 2012 Blackwell Publishing Ltd.
Laboratory of Respiratory Cell Biology, Cardiac, Thoracic and Vascular Department, University of Pisa and University Hospital of Pisa, Pisa, Italy.
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