Starfish polysaccharides downregulate metastatic activity through the MAPK signaling pathway in MCF-7 human breast cancer cells
| Autor: | Kyu-Shik Lee, Kyung-Soo Nam, Jin-Sun Shin |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
MAPK/ERK pathway
medicine.medical_specialty Transcription Genetic MAP Kinase Signaling System Down-Regulation Estrogen receptor Breast Neoplasms Metastasis Starfish Aromatase NF-KappaB Inhibitor alpha Downregulation and upregulation Cell Movement Polysaccharides Internal medicine Genetics medicine Animals Humans Neoplasm Metastasis Phosphorylation Molecular Biology biology NF-kappa B Tissue Inhibitor of Metalloproteinases General Medicine medicine.disease IκBα Endocrinology Matrix Metalloproteinase 9 MCF-7 Cyclooxygenase 2 Cancer cell MCF-7 Cells Cancer research biology.protein Tetradecanoylphorbol Acetate Female I-kappa B Proteins |
| Zdroj: | Molecular Biology Reports. 40:5959-5966 |
| ISSN: | 1573-4978 0301-4851 |
| Popis: | We investigated the effects of starfish (Asterina pectinifera) polysaccharides on metastatic activity in MCF-7 estrogen receptor (ER)-positive human breast cancer cells. In wound healing assay, 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell migration was dose-dependently decreased by the starfish polysaccharides (PS). Transcription of aromatase, which catalyzes estrogen synthesis from androgen, was reduced by PS. Also, transcription of TPA-induced cyclooxygenase-2 (COX-2), which enhances breast cancer progression and metastasis via the increase of prostaglandin E2 biosynthesis, was downregulated by the PS in a dose-dependent manner. PS decreased the expression and activity of matrix metalloproteinase (MMP)-9, an important factor in the degradation of basement membrane and extracellular matrix in the metastasis process. In contrast, mRNA expression of tissue inhibitor of matrix metalloproteinase (TIMP)-1, a MMP inhibitor, was increased by 10-120 μg/ml of PS but not that of TIMP-2. We also found that PS reversed the phosphorylations of p38, ERK and JNK but not IκBα and NF-κB. These results demonstrate that PS successfully inhibits PKC-mediated cell migration and metastatic activities in MCF-7 ER-positive human breast cancer cells via downregulation of MMP-9 activity mediated by TIMP-1 upregulation and inhibition of aromatase and COX-2 expression. Also, COX-2 and MMP-9 expressions are attenuated through the inhibition of AP-1 transcription activity via the downregulation of c-Jun expression regulated by p38, ERK and JNK signaling. In conclusion, the present investigation shows that PS may prevent COX-2- and MMP-9-mediated metastatic activities in MCF-7 ER-positive breast cancer cells through the downregulation of MAPK signaling pathways. |
| Databáze: | OpenAIRE |
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