RRC ID 61782
Author Sonoki H, Tanimae A, Endo S, Matsunaga T, Furuta T, Ichihara K, Ikari A.
Title Kaempherol and Luteolin Decrease Claudin-2 Expression Mediated by Inhibition of STAT3 in Lung Adenocarcinoma A549 Cells.
Journal Nutrients
Abstract Claudin-2 is highly expressed in human lung adenocarcinoma tissues and may be a novel target for cancer chemotherapy because knockdown of claudin-2 decreases cell proliferation. We found that flavonoids including kaempferol, chrysin, and luteolin concentration-dependently decrease claudin-2 expression in lung adenocarcinoma A549 cells. Claudin-2 expression is up-regulated by mitogen-activated protein kinase kinase (MEK)/ extracellular signal-regulated kinase (ERK)/c-Fos and phosphoinositide 3-kinase (PI3K)/Akt/nuclear factor-κB (NF-κB) pathways, but these activities were not inhibited by kaempferol, chrysin, and luteolin. Promoter deletion assay using luciferase reporter vector showed that kaempferol and luteolin inhibit the function of transcriptional factor that binds to the region between -395 and -144 of claudin-2 promoter. The decrease in promoter activity was suppressed by mutation in signal transducers and activators of transcription (STAT)-binding site, which is located between -395 and -144. The phosphorylation level of STAT3 was not decreased, but the binding of STAT3 on the promoter region is suppressed by kaempferol and luteolin in chromatin immunoprecipitation assay. The inhibition of cell proliferation caused by kaempferol and luteolin was partially recovered by ectopic claudin-2 expression. Taken together, kaempferol and luteolin decreased claudin-2 expression and proliferation in A549 cells mediated by the inhibition of binding of STAT3 on the promoter region of claudin-2. The intake of foods and nutrients rich in these flavonoids may prevent lung adenocarcinoma development.
Volume 9(6)
Published 2017-6-13
DOI 10.3390/nu9060597
PII nu9060597
PMID 28608828
PMC PMC5490576
MeSH A549 Cells Adenocarcinoma / metabolism* Antineoplastic Agents / administration & dosage Antineoplastic Agents / pharmacology Claudins / genetics Claudins / metabolism* Gene Expression Regulation, Neoplastic / drug effects Humans Kaempferols / pharmacology* Lung Neoplasms / metabolism* Luteolin / pharmacology* STAT3 Transcription Factor / genetics STAT3 Transcription Factor / metabolism*
IF 4.546
Human and Animal Cells A549