Modulation of HER2 expression by ferulic acid on human breast cancer MCF7 cells

Institute of Traditional Medicine, Veterans General Hospital, Taipei, Taiwan.
European Journal of Clinical Investigation (Impact Factor: 2.73). 09/2006; 36(8):588-96. DOI: 10.1111/j.1365-2362.2006.01676.x
Source: PubMed


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.

10 Reads
    • "In addition, FA derivative feruloyl-L-arabinose (FAA) was also shown to have an effect on H1299 lung cancer cells in attenuating their migration, invasion and reactive oxygen species (ROS) production, suggesting a role for it in chemoprevention just like FA (Fang et al., 2013). On the other hand, despite the chemopreventive functions, FA has also been reported to up-regulate HER2 expression causing proliferation of the human breast cancer cells (Chang et al., 2006). FA also aids in the fight against cancer by increasing the effect of radiation treatment on human cervical carcinoma cells by reducing cell survival and increasing ROS and DNA damage (Karthikeyan et al., 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Novel and combinatorial treatment methods are becoming sought after entities in cancer treatment and these treatments are even more valuable for pancreatic cancer. The scientists are always on the lookout for new chemicals to help them in their fight against cancer. In this study, we examine the effects of ferulic acid (FA), a phenolic compound, on gene expression, viability, colony formation and migration/invasion in the cultured MIA PaCa-2 human pancreatic cancer cell. Cytotoxic effects of FA were determined by using trypan blue dye exclusion test and Cell TiterGlo (CTG) assay. IC50 dose in MIA PaCa-2 cells was detected as 500μM/ml at the 72nd hour. Expression profiles of certain cell cycle and apoptosis genes such as CCND1 (cyclin D1),CDK4, CDK6, RB, p21, p16, p53, caspase-3, caspase-9, caspase-8, caspase-10, Bcl-2, BCL-XL,BID, DR4,DR5,FADD,TRADD,PARP, APAF, Bax, Akt, PTEN, PUMA, NOXA, MMP2, MMP9, TIMP1 and TIMP2 were determined by real-time PCR. The effect of FA on cell viability was determined by CellTiter-Glo® Luminescent Cell Viability Assay. Additionally, effects of FA on colony formation and invasion were also investigated. It was observed that FA caused a significant decrease in the expression of CCND1, CDK 4/6, Bcl2 and caspase 8 and 10 in the MIA PaCa-2 cells while causing an increase in the expression of p53, Bax, PTEN caspase 3 and 9. FA was observed to decrease colony formation while inhibiting cell invasion and migration as observed by the BioCoat Matrigel Invasion Chamber guide and colony formation assays. In conclusion, FA is thought to behave as an anti-cancer agent by affecting cell cycle, apoptotic, invasion and colony formation behavior of MIA PaCa-2 cells. Therefore, FA is placed as a strong candidate for further studies aimed at finding a better, more effective treatment approach for pancreatic cancer.
    No preview · Article · Oct 2015 · Gene
  • Source
    • " case of ECS , gallic , vanillic , O - coumaric , ferulic , cinnamic and sal - icylic acids were identified by HPLC analysis ( Tiwari et al . 2009 ) . Data on the in vitro estrogenic effects of phenolic acids indicate that ferulic acid stimulates pro - liferation of human breast cancer MCF - 7 cells in a concentration - and ER - dependent manner ( Chang et al . 2006 ) . Previously , Kampa et al . ( 2004 ) reported that this phenolic acid showed anti - proliferative action in the T47D breast cancer cell line . In a recent study , gallic acid was reported to show affinity for ERβ but not for ERa ( Hidalgo et al . 2012 ) . Finally , some essen - tial oils have shown in vitro estrogenic and / or anti -"
    [Show abstract] [Hide abstract]
    ABSTRACT: Medicinal plants are widely used for the treatment of diseases and for the development of new drugs. This study was designed to determine the presence of hormone-like activities dependent on the activation of human estrogen receptor alpha (hERa) and/or androgen receptor (hAR) in methanol extracts prepared from three medicinal plants historically and currently used for therapeutic purposes [Ginkgo biloba leaves (GBL), Elettaria cardamomum seeds (ECS), and Plantago ovata seeds (POS)]. After a solid-liquid extraction (SLE) step, their effects on hERa function were assessed in MCF-7 breast cancer cells using the E-Screen bioassay, and their ability to induce hAR-mediated reporter gene expression was evaluated using the androgen-sensitive stable prostatic PALM cell line. Unlike POS extracts, GBL and ECS extracts showed estrogenic (0.07 and 0.20 nM E2Eq/mg, respectively) and anti-estrogenic (0.01 and 0.02 μM ICI182780Eq/mg, respectively) activities. ECS extracts evidenced androgenic activity (0.30 nM R1881Eq/mg) and POS extracts anti-androgenic activity (22.30 μM ProcEq/mg). According to these findings, these plant extracts may interfere with the endocrine system via one or more hormonal receptors, and further investigation is warranted into their role as endocrine disrupters in humans.
    Full-text · Article · Jul 2015 · Food Additives and Contaminants - Part A Chemistry, Analysis, Control, Exposure and Risk Assessment
  • Source
    • "The only difference in the identified polyphenols between the Mavrotragano variety extract and the other extracts was that the former contained at least 6-fold more ferulic acid. Importantly, other studies have shown that ferulic acid induces MCF-7 cell growth through an estrogen dependent mechanism (Hao et al., 2010; Chang et al., 2006). Thus, it is inferred from the above that the polyphenolic composition of the grape stem extracts affects their inhibition against different breast cancer cell types. "
    [Show abstract] [Hide abstract]
    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.
    Full-text · Article · Oct 2014 · Toxicology Letters
Show more