Magnolol down-regulates HER2 gene expression, leading to inhibition of HER2-mediated metastatic potential in ovarian cancer cells
| Autor: | Vinchi Wang, Chien Chih Ou, Shih Chung Hsu, Yi Ting Cheng, Wei Syun Shao, Kuohui Wu, Tzu-Chao Chuang, Guan Shiun Fang |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Vascular Endothelial Growth Factor A
Cancer Research Receptor ErbB-2 Angiogenesis Down-Regulation Cell Growth Processes Biology Lignans Metastasis Phosphatidylinositol 3-Kinases chemistry.chemical_compound Cell Line Tumor medicine Humans Cyclin D1 Neoplasm Metastasis skin and connective tissue diseases PI3K/AKT/mTOR pathway Ovarian Neoplasms Oncogene Caspase 3 Akt/PKB signaling pathway TOR Serine-Threonine Kinases Biphenyl Compounds Genes erbB-2 medicine.disease Magnolol Gene Expression Regulation Neoplastic Cell Transformation Neoplastic Oncology chemistry Cancer cell Cancer research Female Poly(ADP-ribose) Polymerases Ovarian cancer Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Cancer Letters. 311:11-19 |
| ISSN: | 0304-3835 |
| Popis: | Overexpression of the HER2 oncogene contributes to tumor cell invasion, metastasis and angiogenesis and correlates with poor prognosis. Magnolol has been reported to exhibit anti-tumor activities. However, the molecular mechanism of action of magnolol has not been investigated in HER2-positive cancer cells. Therefore, we examined the anti-cancer effects of magnolol on HER2-overexpressing ovarian cancer cells. Magnolol treatment caused a dose-dependent inhibition of HER2 gene expression at the transcriptional level, potentially in part through suppression of NF-κB activation. Treatment of HER2-overexpressing ovarian cancer cells with magnolol down-regulated the HER2 downstream PI3K/Akt signaling pathway, and suppressed the expression of downstream target genes, vascular endothelial growth factor (VEGF), matrix metalloproteinase 2 (MMP2) and cyclin D1. Consistently, magnolol-mediated inhibition of MMP2 activity could be prevented by co-treatment with epidermal growth factor. Migration assays revealed that magnolol treatment markedly reduced the motility of HER2-overexpressing ovarian cancer cells. Furthermore, magnolol-induced apoptosis in HER2-overexpressing ovarian cancer cells was characterized by the up-regulation of cleaved poly(ADP-ribose) polymerase (PARP) and activated caspase 3. These findings suggest that magnolol may act against HER2 and its downstream PI3K/Akt/mTOR-signaling network, thus resulting in suppression of HER2-mediated transformation and metastatic potential in HER2-overexpressing ovarian cancers. These results provide a novel mechanism to explain the anti-cancer effect of magnolol. |
| Databáze: | OpenAIRE |
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