화학공학소재연구정보센터
Biochemical and Biophysical Research Communications, Vol.468, No.4, 574-579, 2015
24-Methylenecycloartanyl ferulate, a major compound of gamma-oryzanol, promotes parvin-beta expression through an interaction with peroxisome proliferator-activated receptor-gamma 2 in human breast cancer cells
Parvin-beta is an adaptor protein that binds to integrin-linked kinase (ILK) and is significantly down-regulated in breast tumors and breast cancer cell lines. We treated the breast cancer cell line MCF7 with 24-methylenecycloartanyl ferulate (24-MCF), a gamma-oryzanol compound. We observed upregulation of parvin-beta (GenBank Accession No. AF237769) and peroxisome proliferator-activated receptor (PPAR)-gamma 2 (GenBank Accession No. NM_015869). Among gamma-oryzanol compounds, only treatment with 24-MCF led to the formation of reverse transcription-PCR products of parvin-beta (650 and 500 bp) and PPAR-gamma 2 (580 bp) in MCF7 cells, but not in T47D, SK-BR-3, or MDA-MB-231 cells. 24-MCF treatment increased the mRNA and protein levels of parvin-beta in MCF7 cells in a dose-dependent manner. We hypothesized that there is a correlation between parvin-beta expression and induction of PPAR-gamma 2. This hypothesis was investigated by using a promoter-reporter assay, chromatin immunoprecipitation, and an electrophoretic mobility shift assay. 24-MCF treatment induced binding of PPAR-gamma 2 to a peroxisome proliferator response element-like cis-element (ACTAGGACAAAGGACA) in the parvin-beta promoter in MCF7 cells in a dose-dependent manner. 24-MCF treatment significantly decreased anchorage-independent growth and inhibited cell movement in comparison to control treatment with dimethyl sulfoxide. 24-MCF treatment reduced the levels of GTP-bound Racl and Cdc42. Evaluation of Alai inhibition by 24-MCF revealed that the half maximal effective concentration was 33.3 mu M. Docking evaluations revealed that 24-MCF binds to the ATP-binding site of Aktl(PDB ID: 30CB) and the compound binding energy is -8.870 kcal/mol. Taken together, our results indicate that 24-MCF treatment increases parvin-beta expression, which may inhibit ILK downstream signaling. (C) 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).