Document Detail

Differential inhibition of protein translation machinery by curcumin in normal, immortalized, and malignant oral epithelial cells.
MedLine Citation:
PMID:  20145189     Owner:  NLM     Status:  MEDLINE    
Curcumin has shown some promise in the prevention of oral carcinogenesis by mechanism(s) that are still not completely resolved. Messenger RNA translation is mediated in eukaryotes by the eIF4F complex composed of eukaryotic translation initiation factors eIF4E, eIF4G, and eIF4A. Overexpression of some of these components or the inactivation of initiation repressor proteins (4E-BP1) has been implicated in cancer development including oral carcinogenesis by affecting cell survival, angiogenesis, and tumor growth and invasion. In this study, we examined the possibility that curcumin affects the translational machinery differently in normal, immortalized normal, leukoplakia, and malignant cells. Curcumin treatment in vitro inhibited the growth of immortalized oral mucosa epithelial cells (NOM9-CT) and the leukoplakia cells (MSK-Leuk1s) as well as in the UMSCC22B and SCC4 cells derived from head and neck squamous cell carcinoma. Curcumin only exerted minor effects on the growth of normal oral epithelial cells (NOM9). In the immortalized, leukoplakia, and cancer cells, curcumin inhibited cap-dependent translation by suppressing the phosphorylation of 4E-BP1, eIF4G, eIF4B, and Mnk1, and also reduced the total levels of eIF4E and Mnk1. Our findings show that immortalized normal, leukoplakia, and malignant oral cells are more sensitive to curcumin and show greater modulation of protein translation machinery than the normal oral cells, indicating that targeting this process may be an important approach to chemoprevention in general and for curcumin in particular.
Nitin Chakravarti; Humam Kadara; Do-Jun Yoon; Jerry W Shay; Jeffrey N Myers; Dafna Lotan; Nahum Sonenberg; Reuben Lotan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-02-09
Journal Detail:
Title:  Cancer prevention research (Philadelphia, Pa.)     Volume:  3     ISSN:  1940-6215     ISO Abbreviation:  Cancer Prev Res (Phila)     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-05     Completed Date:  2010-06-08     Revised Date:  2014-05-02    
Medline Journal Info:
Nlm Unique ID:  101479409     Medline TA:  Cancer Prev Res (Phila)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  331-8     Citation Subset:  IM    
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MeSH Terms
Adaptor Proteins, Signal Transducing / antagonists & inhibitors,  metabolism
Antineoplastic Agents / pharmacology*
Blotting, Western
Cell Line, Transformed / cytology,  drug effects*
Cell Proliferation / drug effects
Cells, Cultured
Curcumin / pharmacology*
Eukaryotic Initiation Factor-4G / antagonists & inhibitors,  metabolism
Eukaryotic Initiation Factors / antagonists & inhibitors,  metabolism
Intracellular Signaling Peptides and Proteins / antagonists & inhibitors,  metabolism
Mouth Mucosa / drug effects*
Peptide Chain Initiation, Translational / drug effects*
Phosphoproteins / antagonists & inhibitors,  metabolism
Phosphorylation / drug effects
Precancerous Conditions / drug therapy*,  pathology
Protein Biosynthesis / drug effects
Protein-Serine-Threonine Kinases / antagonists & inhibitors,  metabolism
Grant Support
CA106451/CA/NCI NIH HHS; P01 CA106451/CA/NCI NIH HHS; P01 CA106451-01/CA/NCI NIH HHS
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Antineoplastic Agents; 0/EIF4EBP1 protein, human; 0/EIF4G1 protein, human; 0/Eukaryotic Initiation Factor-4G; 0/Eukaryotic Initiation Factors; 0/Intracellular Signaling Peptides and Proteins; 0/Phosphoproteins; 0/eIF-4B; EC 2.7.1.-/MKNK1 protein, human; EC Kinases; IT942ZTH98/Curcumin

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

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