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Abstract Title:

Differential inhibition of protein translation machinery by curcumin in normal, immortalized, and malignant oral epithelial cells.

Abstract Source:

Cancer Prev Res (Phila). 2010 Mar;3(3):331-8. Epub 2010 Feb 9. PMID: 20145189

Abstract Author(s):

Nitin Chakravarti, Humam Kadara, Do-Jun Yoon, Jerry W Shay, Jeffrey N Myers, Dafna Lotan, Nahum Sonenberg, Reuben Lotan

Article Affiliation:

Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

Abstract:

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.

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Sayer Ji
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