Document Detail

Sodium butyrate induces retinoblastoma protein dephosphorylation, p16 expression and growth arrest of colon cancer cells.
MedLine Citation:
PMID:  9823007     Owner:  NLM     Status:  MEDLINE    
Sodium butyrate causes alteration of colon cancer cell morphology and biology towards that of a more differentiated phenotype. The retinoblastoma gene encodes a nuclear phosphoprotein (pRb) present in a wide range of human cancer cell lines including colon cancer cell lines. pRB is synthesized throughout the cell cycle and phosphorylated in a phase specific manner: the predominant proteins in G0/G1 are the unphosphorylated species (110 kD) whereas phosphorylated pRb (112-114 kD) are in S and G2. 110 kD pRb binds transcription factors and prevents transcription of responsive genes such as the gene for thymidine kinase, which are expressed in late G1. The precise mechanisms controlling cell arrest are unknown, but recent data suggest that cyclin-dependent kinase inhibitors such as p16 may play a role. The aim of the present study was to assess the effect of sodium butyrate on cell cycle staging, thymidine kinase activity, phosphorylation of the pRb protein and expression of p16. We show that sodium butyrate treatment induces differentiation of LS174T colon cancer cells, inhibits thymidine kinase activity concomitantly with induction of pRb dephosphorylation, p16 transcription and cell cycle arrest at G0/G1. Initial dephosphorylation was observed 24 h after treatment of LS174T cells with sodium butyrate, whereas complete shift to the dephosphorylated form was observed 3 days after treatment. Induction of pRb dephosphorylation by sodium butyrate preceded inhibition of growth and the specific cell cycle arrest. RNase protection assay with a p16 specific riboprobe showed undetectable levels in proliferating cells to several fold increase in differentiated colonocytes. In conclusion, the results provide evidence for a specific cellular mechanism of butyrate induced growth arrest and differentiation of a colon cancer cell line.
B Schwartz; C Avivi-Green; S Polak-Charcon
Related Documents :
9458357 - P53-independent down-regulation of cyclin d1 and p21waf1 in the process of immortalizat...
10502407 - Lovastatin inhibits g1/s transition of normal human b-lymphocytes independent of apopto...
9284557 - Cyclins in a dinoflagellate cell cycle.
11243867 - Msx1 gene overexpression induces g1 phase cell arrest in human ovarian cancer cell line...
21552907 - Characterization of glioma-cells derived from human polyomavirus-induced brain-tumors i...
24338187 - The biology of zinc transport in mammary epithelial cells: implications for mammary gla...
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Molecular and cellular biochemistry     Volume:  188     ISSN:  0300-8177     ISO Abbreviation:  Mol. Cell. Biochem.     Publication Date:  1998 Nov 
Date Detail:
Created Date:  1999-02-05     Completed Date:  1999-02-05     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0364456     Medline TA:  Mol Cell Biochem     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  21-30     Citation Subset:  IM    
Institute of Biochemistry, Food Science and Nutrition, Faculty of Agriculture, Food and Environmental Quality Sciences, Hebrew University of Jerusalem, Israel.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Alkaline Phosphatase / metabolism
Butyric Acids / pharmacology*
Cell Differentiation / drug effects
Cell Division / drug effects
Colonic Neoplasms / pathology*,  ultrastructure
Cyclin-Dependent Kinase Inhibitor p16 / genetics,  metabolism*
Cyclin-Dependent Kinases / physiology
Growth Substances / pharmacology
Phosphorylation / drug effects
Retinoblastoma Protein / metabolism*
Transcription, Genetic / drug effects
Tumor Cells, Cultured
Reg. No./Substance:
0/Butyric Acids; 0/Cyclin-Dependent Kinase Inhibitor p16; 0/Growth Substances; 0/Retinoblastoma Protein; EC Kinases; EC Phosphatase

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

Previous Document:  Dissociation of vitamin D3 and anti-estrogen mediated growth regulation in MCF-7 breast cancer cells...
Next Document:  Regulation of adipocyte gene expression by polyunsaturated fatty acids.