Curcumin modulates eukaryotic initiation factors in human lung adenocarcinoma epithelial cells.
Curcumin, a polyphenolic compound, is the active component of Curcuma longa and has been extensively investigated as an anticancer drug that modulates multiple pathways. Eukaryotic initiation factors (eIFs) have been known to play important roles in translation initiation, which controls cell growth and proliferation. Little is known about the effects of curcumin on eIFs in lung cancer. The objective of this study was to exam the curcumin cytotoxic effect and modulation of two major rate-limiting translation initiation factors, including eIF2α and eIF4E protein expression levels in lung adenocarcinoma epithelial cell line A549. Cytotoxicity was measured by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and protein changes were determined by Western blot. A549 cells were treated with 0-240 μM curcumin for 4-96 h. The inhibitory effects of curcumin on cytotoxicity were dose- and time-dependent (P < 0.001). The 50% inhibitory curcumin concentrations (IC50s) at 24, 48, 72, and 96 h were 93, 65, 40, and 24 μM, respectively. Protein expressions of eIF2α, eIF4E, Phospho-4E-BP1 were down-regulated, while Phospho-eIF2α and Phospho-eIF4E were up-regulated after A549 cells were treated with 20 and 40 μM curcumin for 24 h. In addition, the effects of curcumin on these protein expression changes followed a significant dose-response (P < 0.05, trend test). These findings suggest that curcumin could reduce cell viability through prohibiting the initiation of protein synthesis by modulating eIF2α and eIF4E.
Chen
Lixia
L
Department of Environmental Toxicology and The Institute of Environmental and Human Health, Texas Tech University, Lubbock, TX 79409, USA.
Tian
Guoqing
G
Shao
Changxia
C
Cobos
Everardo
E
Gao
Weimin
W
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D039642:Eukaryotic Initiation Factors / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D015852:Eukaryotic Initiation Factor-2; D039561:Eukaryotic Initiation Factor-4E; D039642:Eukaryotic Initiation Factors; D010750:Phosphoproteins; D003474:Curcumin