Modulation of HER2 expression by ferulic acid on human breast cancer MCF7 cells.
ABSTRACT The molecular mechanisms underlying the mitogenic effect of ferulic acid (FA), an active compound derived from Angelica sinensis, have never been elucidated. It was the aim of this study to investigate the proliferative effect of FA on human breast cancer cell lines and to elucidate its modulation mechanism on HER2 expression in MCF7 line.
By using MCF7 (oestrogen receptor-positive; ER+, HER2-low), BT474 (ER+, HER2-high), MDAMB231 (ER-, HER2-low) and SKBR3 (ER-, HER2-high) human breast cancer cell lines as in vitro models, the mitogenic effects of FA were assessed by trypan blue dye exclusion assay and DNA flow cytometry. Ferulic acid-modulated cell signalling and HER2 gene expression were evaluated in MCF7 line by Western blot and real-time RT-PCR analysis.
Ferulic acid ER-dependently stimulated cell proliferation on MCF7 cells in a concentration-dependent manner. The HER2 oncogene (one of the prognostic factors of breast cancer) and ESR1 gene (oestrogen receptor-alpha; ERalpha) transcription were markedly up-regulated by FA treatment. Besides, HER2 signalling and its downstream molecules such as AKT and ERK1/2 were involved in FA-modulated ERalpha and cyclin D1 synthesis. Addition of anti-HER2 antibody, trastuzumab, abrogated FA-enhanced proliferative effect on MCF7 cells, indicated a positive feedback control for the action of HER2 in this setting. The fact that the ER antagonist blocked most of the FA-up-regulated HER2 expression, and that trastuzumab down-regulated ERalpha gene expression, suggested a cross-talk between ERalpha and HER2 signalling on MCF7 cells.
The authors' conclude that FA causes human breast cancer cell proliferation by up-regulation of HER2 and ERalpha expression.
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ABSTRACT: A major part of the wineries’ wastes is composed of grape stems which are discarded mainly in open fields and cause environmental problems due mainly to their high polyphenolic content. The grape stem extracts’ use as a source of high added value polyphenols presents great interest because this combines a profitable venture with environmental protection close to wine-producing zones. In the present study, at first, the Total Polyphenolic Content (TPC) and the polyphenolic composition of grape stem extracts from four different Greek Vitis vinifera varieties were determined by HPLC methods. Afterwards, the grape stem extracts were examined for their ability to inhibit growth of colon (HT29), breast (MCF-7 and MDA-MB-23), renal (786-0 and Caki-1) and thyroid (K1) cancer cells. The cancer cells were exposed to the extracts for 72 h and the effects on cell growth were evaluated using the SRB assay. The results indicated that all extracts inhibited cell proliferation, with IC50 values of 121-230 μg/ml (MCF-7), 121-184 μg/ml (MDA-MD-23), 175-309 μg/ml (HT29), 159-314 μg/ml (K1), 180-225 μg/ml (786-0) and 134 - >400 μg/ml (Caki-1). This is the first study presenting the inhibitory activity of grape stem extracts against growth of colon, breast, renal and thyroid cancer cells.Toxicology Letters 10/2014; 230(2). DOI:10.1016/j.toxlet.2014.01.042 · 3.36 Impact Factor
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ABSTRACT: Fibrosarcoma belongs to the sarcoma cancer group, which are spindle cell malignancies of mesenchymal origin, and owe their name to the predominant cell line that is present within the tumor. The extracellular matrix (ECM) is a complicated structure that surrounds and supports cells within tissues. Its main components are proteoglycans, collagens, glycoproteins, hyaluronan (HA), and several matrix-degrading enzymes. During cancer progression, significant changes can be observed in the structural and mechanical properties of ECM components. The ECM provides a physical scaffold to which tumor cells attach and migrate. Thus, it is required for key cellular events such as cell motility, adhesion, proliferation, invasion, and metastasis. Importantly, fibrosarcomas were shown to have a high content and turnover of ECM components including HA, proteoglycans, collagens, fibronectin, and laminin. In this review, we will focus on the HA component of fibrosarcoma ECM and critically discuss its role and involved mechanisms during fibrosarcoma pathogenesis.Advances in Cancer Research 01/2014; 123:319-49. DOI:10.1016/B978-0-12-800092-2.00012-5 · 4.26 Impact Factor