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KMID : 1140120080130020108
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Cancer Prevention Research
2008 Volume.13 No. 2 p.108 ~ p.115
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Kalopanaxsaponin A Inhibits the Invasion of MDA-MB-231 Human Metastatic Breast Cancer Cells
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Hwang Young-Sun
Park Kwang-Kyun
Park Hee-Juhn
Chung Won-Yoon
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Abstract
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Invasion and metastasis of cancer cells are the leading cause of death for cancer patients, and matrix metalloproteinases (MMPs) play an important role in these steps. In this study, we determined the effect of kalopanaxsaponin A (KPS-A), isolated from the stem bark of Kalopanax pictus Nakai, on the invasion of MDA-MB-231 human metastatic breast cancer cells. KPS-A significantly inhibited the viability and PMA-induced invasion of MDA-MB-231 cells in dose-related manner. We also found that PMA-induced invasion was suppressed by KPS-A through decreasing the MMP-9 secretion. In addition, KPS-A remarkably reduced PMA-induced DNA binding and transcriptional activity of nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1), and blocked PMA-induced phosphorylation of ERK1/2 and Akt, not p38 MAPK. Furthermore, we confirmed that PMA-induced MMP-9 activity and transcriptional activity of NF-κB and AP-1 were regulated by p38 MAPK, Akt, ERK1/2. Taken together, the suppression of MMP-9 activity through ERK1/2/AP-1 and Akt/NF-κB pathway may contribute to the anti-invasion activity of KPS-A in PMA-stimulated MDA-MB-231 cells. (Cancer Prev Res 13, 108-115, 2008)
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KEYWORD
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Kalopanaxsaponin A, PMA-induced invasion, Matrix metalloproteinase-9
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