Document Detail


Additive inhibition of colorectal cancer cell lines by aspirin and bortezomib.
MedLine Citation:
PMID:  20397022     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: To investigate the effect of cyclooxygenase-2 (Cox-2) inhibitor aspirin (acetylsalicylic acid, ASA) and proteasome inhibitor bortezomib in the proliferation and apoptosis of colorectal cancer cell lines. METHODS: MTT assay, trypan blue exclusion and DNA fragmentation have been used to investigate cell proliferation and apoptosis in the presence of drugs. For the determination of Cox activity a colorimetric method was used. Western blotting was used for the measurement of the effect of the drugs in different proteins expression. RESULTS: Bortezomib together with aspirin inhibit the growth of colorectal cancer cell lines HCT116, HT-29, and CaCo2 more than each drug alone. In the first two cell lines ASA inhibitory effects are Cox-2 independent because HCT116 cells do not express the enzyme while in HT-29 cells, Cox-2 has no activity as shown by a Cox activity assay. In CaCo2 cells that express enzymatically active Cox-2 this activity is inhibited by ASA. ASA is also able to suppress the increase in Cox-2 activity induced by bortezomib in these cells. Cell cycle inhibitors p21 and p27 are induced in the three cell lines by bortezomib and the combination treatment. Akt1 kinase is down-regulated in all three lines by the same treatments. Transcription factor NF-kappaB is retained in the cytoplasm by drug treatment in cell lines HCT116 and HT-29, a fact that may play a role in their pro-apoptotic activity. Pro-apoptotic bcl-2 family member, bad is down-regulated in cell lines HCT116 and CaCo2 by bortezomib treatment, a neoplasia-promoting event that is reversed by combination treatment. CONCLUSION: The combination of bortezomib and ASA cooperates to decrease proliferation and induce apoptosis in three human colorectal cell lines with different genetic lesions. These effects are at least in some cases Cox-2 independent and involve common and diverse mechanisms in the three lines.
Authors:
Ioannis A Voutsadakis; Anna Patrikidou; Konstantinos Tsapakidis; Aristea Karagiannaki; Eleana Hatzidaki; Nikolaos E Stathakis; Christos N Papandreou
Publication Detail:
Type:  Journal Article     Date:  2010-04-16
Journal Detail:
Title:  International journal of colorectal disease     Volume:  25     ISSN:  1432-1262     ISO Abbreviation:  Int J Colorectal Dis     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-02     Completed Date:  2010-09-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8607899     Medline TA:  Int J Colorectal Dis     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  795-804     Citation Subset:  IM    
Affiliation:
Division of Medical Oncology, University Hospital of Larissa, Larissa, Greece. ivoutsadakis@yahoo.com
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects
Aspirin / pharmacology*
Blotting, Western
Boronic Acids / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
Colorectal Neoplasms / enzymology,  pathology*
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
Cyclin-Dependent Kinase Inhibitor p27 / metabolism
Cyclooxygenase 2 / metabolism
Down-Regulation / drug effects
Drug Synergism
Humans
NF-kappa B / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Pyrazines / pharmacology*
bcl-Associated Death Protein / metabolism
Chemical
Reg. No./Substance:
0/Boronic Acids; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/NF-kappa B; 0/Pyrazines; 0/bcl-Associated Death Protein; 0/bortezomib; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; 50-78-2/Aspirin; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/PTGS2 protein, human; EC 2.7.11.1/Proto-Oncogene Proteins c-akt

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


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