Abstract
BackgroundRecently, Abeliophyllum distichum Nakai (A. distichum) has been reported to exert the inhibitory effect on angiotensin converting enzyme. However, no specific pharmacological effects from A. distichum have been described. We performed in vitro study to evaluate anti-cancer properties of A. distichum and then elucidate the potential mechanisms.MethodsCell viability was measured by MTT assay. ATF3 expression level was evaluated by Western blot or RT-PCR and ATF3 transcriptional activity was determined using a dual-luciferase assay kit after the transfection of ATF3 promoter constructs. In addition, ATF3-dependent apoptosis was evaluated by Western blot after ATF3 knockdown using ATF3 siRNA.ResultsExposure of ethyl acetate fraction from the parts of A. distichum including flower, leaf and branch to human colorectal cancer cells, breast cancer cells and hepatocellular carcinoma reduced the cell viability. The branch extracts from A. distichum (EAFAD-B) increased the expression of activating transcription factor 3 (ATF3) and promoter activity, indicating transcriptional activation of ATF3 gene by EAFAD-B. In addition, our data showed that EAFAD-B-responsible sites might be between -147 and -85 region of the ATF3 promoter. EAFAD-B-induced ATF3 promoter activity was significantly decreased when the CREB site was deleted. However, the deletion of Ftz sites did not affect ATF3 promoter activity by EAFAD-B. We also observed that inhibition of p38MAPK and GSK3β attenuated EAFAD-B-mediated ATF3 promoter activation. Also, EAFAD-B contributes at least in part to increase of ATF3 accumulation.ConclusionThese findings suggest that the anti-cancer activity of EAFAD-B may be a result of ATF3 promoter activation and subsequent increase of ATF3 expression.
Highlights
Abeliophyllum distichum Nakai (A. distichum) has been reported to exert the inhibitory effect on angiotensin converting enzyme
A. distichum induces reduction of cell viability against various cancer cells The effects of the ethyl acetate fraction from the parts of A. distichum on cell viability were evaluated in human breast cancer cells (MCF-7 and MDA-MB-231), colorectal cancer cells (HCT116 and SW480), hepatocellular carcinoma cells (HepG-2) and colon normal cells (CCD-18co) by MTT assay
To identify the role of each cis-acting element affecting EAFAD-B-mediated activating transcription factor 3 (ATF3) transcriptional activation, each site-deleted ATF3 promoter constructs were transfected into HCT116 and SW480 cells and we found that EAFAD-B-induced ATF3 promoter activity was significantly decreased when the CREB site was deleted
Summary
Abeliophyllum distichum Nakai (A. distichum) has been reported to exert the inhibitory effect on angiotensin converting enzyme. A. distichum has been reported to exert the inhibitory effect on angiotensin converting enzyme [1]. There are growing evidences to suggest that ATF3 is expressed in cells treated with serum and growth factor and induces DNA synthesis and expression of cyclin D1 in hepatocytes [5,6]. ATF3 activates the canonical Wnt/β-catenin pathway in human breast cancer cell [7]. ATF3 activation promotes a proapoptotic response, as there are evidences to suggest that ATF3 overexpression induced apoptosis in human colorectal cancer cells [8,9,10]. It is suggested that ATF3 activation may be a promising cancer preventive and therapeutic target in human colorectal cancer
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