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The chemopreventive agent ursodeoxycholic acid inhibits proliferation of colon carcinoma cells by suppressing c-Myc expression.
MedLine Citation:
PMID:  22395148     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Ursodeoxycholic acid (UDCA) can prevent chemical and colitis-associated colon carcinogenesis by unknown mechanism(s). One of the processes underlying the chemopreventive action could be the inhibition of proliferation by UDCA. To clarify the antiproliferative mechanism of UDCA, we used p53 colon carcinoma cell lines HCT8 and HCT116. UDCA-induced inhibition of proliferation was reversible and was associated with a decrease of the S-phase and an increase of G1 phase population, but not with apoptosis or senescence. The treatment suppressed the expression of c-Myc protein and, as a consequence, of several cell cycle regulatory molecules, including CDK4 and CDK6. Using the HCT8 cell line as a model, we show that UDCA suppresses c-Myc at the protein level. The suppression of c-Myc alone or a simultaneous suppression of CDK4 and of CDK6 kinase is sufficient to inhibit cell proliferation. In sum, we identified c-Myc as a primary UDCA target in colon carcinoma cells. The degradation of c-Myc protein decreases the expression of the cell cycle regulators CDK4 and CDK6, which reversibly slows down the cell cycle. The suppression of these proproliferatory molecules is the likely initial mechanism of antiproliferatory action of UDCA on colon cancer cells.
Authors:
Roser Peiró-Jordán; Santosh Krishna-Subramanian; Marie-Luise Hanski; Juliane Lüscher-Firzlaff; Martin Zeitz; Christoph Hanski
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-4
Journal Detail:
Title:  European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)     Volume:  -     ISSN:  1473-5709     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-3-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9300837     Medline TA:  Eur J Cancer Prev     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
aDepartment of Gastroenterology, Charité Campus Benjamin Franklin, Berlin, Germany bInstitute of Chemistry and Biochemistry, Free University Berlin, Berlin cInstitute of Biochemistry and Molecular Biology, University Clinic Aachen, Aachen, Germany.
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