RRC ID 56160
Author Sonoki H, Tanimae A, Furuta T, Endo S, Matsunaga T, Ichihara K, Ikari A.
Title Caffeic acid phenethyl ester down-regulates claudin-2 expression at the transcriptional and post-translational levels and enhances chemosensitivity to doxorubicin in lung adenocarcinoma A549 cells.
Journal J Nutr Biochem
Abstract Claudin-2 is highly expressed in human lung adenocarcinoma cells and involved in the promotion of proliferation. Here, we searched for a compound, which can decrease claudin-2 expression using lung adenocarcinoma A549 cells. In the screening using compounds included in royal jelly and propolis, the protein level of claudin-2 was dose-dependently decreased by caffeic acid phenethyl ester (CAPE), whereas the mRNA level and promoter activity were only decreased by 50 μM CAPE. These results suggest that CAPE down-regulates claudin-2 expression mediated by two different mechanisms. CAPE (50 μM) decreased the level of p-NF-κB, whereas it increased that of IκB. The CAPE-induced decrease in promoter activity of claudin-2 was blocked by the mutation in an NF-κB-binding site. The inhibition of NF-κB may be involved in the decrease in mRNA level of claudin-2. The CAPE (10 μM)-induced decrease in claudin-2 expression was inhibited by chloroquine, a lysosomal inhibitor. CAPE increased the expression and activity of protein phosphatase (PP) 1 and 2A. The CAPE-induced decrease in claudin-2 expression was blocked by cantharidin, a potent PPs inhibitor. The cell proliferation was suppressed by CAPE, which was partially rescued by ectopic expression of claudin-2. In addition, the toxicity and accumulation of doxorubicin in 3D spheroid cells were enhanced by CAPE, which was inhibited by ectopic expression of claudin-2. Taken together, CAPE down-regulates claudin-2 expression at the transcriptional and post-translational levels, and enhances sensitivity of cells to doxorubicin in 3D culture conditions. CAPE may be a useful adjunctive compound in the treatment of lung adenocarcinoma.
Volume 56
Pages 205-214
Published 2018-6
DOI 10.1016/j.jnutbio.2018.02.016
PII S0955-2863(17)30782-9
PMID 29597147
MeSH A549 Cells Adenocarcinoma of Lung / drug therapy Adenocarcinoma of Lung / metabolism* Caffeic Acids / chemistry* Cantharidin / chemistry Cell Line, Tumor Cell Proliferation Chloroquine / chemistry Claudins / metabolism* Down-Regulation Doxorubicin / chemistry Doxorubicin / pharmacology* Drug Synergism Fatty Acids / chemistry Gene Expression Regulation* Humans Lung Neoplasms / drug therapy Lung Neoplasms / metabolism* Lysosomes / chemistry Permeability Phenylethyl Alcohol / analogs & derivatives* Phenylethyl Alcohol / chemistry Promoter Regions, Genetic Propolis / chemistry RNA, Messenger / metabolism Tight Junctions
IF 4.414
Times Cited 3
Human and Animal Cells A549