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Starfish polysaccharides downregulate metastatic activity through the MAPK signaling pathway in MCF-7 human breast cancer cells

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Abstract

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.

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Acknowledgments

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0025010).

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  1. Department of Pharmacology, College of Medicine and Intractable Disease Research Center, Dongguk University, Gyeongju, 780-714, Korea

    Kyu-Shik Lee, Jin-Sun Shin & Kyung-Soo Nam

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  1. Kyu-Shik Lee
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  2. Jin-Sun Shin
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Correspondence to Kyung-Soo Nam.

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Lee, KS., Shin, JS. & Nam, KS. Starfish polysaccharides downregulate metastatic activity through the MAPK signaling pathway in MCF-7 human breast cancer cells. Mol Biol Rep 40, 5959–5966 (2013). https://doi.org/10.1007/s11033-013-2705-1

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  • DOI: https://doi.org/10.1007/s11033-013-2705-1

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