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Molecules 2014, 19(10), 16588-16608; doi:10.3390/molecules191016588

Deguelin Inhibits the Migration and Invasion of U-2 OS Human Osteosarcoma Cells via the Inhibition of Matrix Metalloproteinase-2/-9 in Vitro

1
Department of Pathology, National Defense Medical Center, Division of Clinical Pathology, Tri-Service General Hospital, Taipei 114, Taiwan
2
Department of Medical Laboratory Science and Biotechnology, Yuanpei University, Hsinchu 300, Taiwan
3
Department of Biological Science and Technology, China Medical University, No 91, Hsueh-Shih Road, Taichung 404, Taiwan
4
School of Chinese Medicine, China Medical University, Taichung 404, Taiwan
5
Department of Research and Education, Cheng-Hsin General Hospital, No.45, Cheng Hsin St., Pai-Tou, Taipei 112, Taiwan
6
Department of Clinical Pathology, Cheng-Hsin General Hospital, Taipei 112, Taiwan
7
School of Pharmacy, China Medical University, Taichung 404, Taiwan
8
Department of Restaurant, Hotel and Institutional Management, Fu-Jen Catholic University, New Taipei City 242, Taiwan
9
Department of Orthopedic Surgery, Cheng-Hsin General Hospital, Taipei 112, Taiwan
10
Department of Biotechnology, Asia University, Taichung 413, Taiwan
*
Authors to whom correspondence should be addressed.
Received: 15 August 2014 / Revised: 16 September 2014 / Accepted: 23 September 2014 / Published: 15 October 2014
(This article belongs to the Section Medicinal Chemistry)
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Abstract

Osteosarcoma is the most common malignant primary bone tumor in children and young adults and lung metastasis is the main cause of death in those patients. Deguelin, a naturally occurring rotenoid, is known to be an Akt inhibitor and to exhibit cytotoxic effects, including antiproliferative and anticarcinogenic activities, in several cancers. In the present study, we determined if deguelin would inhibit migration and invasion in U-2 OS human osteosarcoma cells. Deguelin significantly inhibited migration and invasion of U-2 OS human osteosarcoma cells which was associated with a reduction of activities of matrix metalloproteinases-2 (MMP-2) and matrix metalloproteinases-9 (MMP-9). Furthermore, results from western blotting indicated that deguelin decreased the cell proliferation and cell growth-associated protein levels, such as SOS1, PKC, Ras, PI3K, p-AKT(Ser473), IRE-1α, MEKK3, iNOS, COX2, p-ERK1/2, p-JNK1/2, p-p38; the cell motility and focal adhesion-associated protein levels, such as Rho A, FAK, ROCK-1; the invasion-associated protein levels, such as TIMP1, uPA, MMP-2. MMP-9, MMP-13, MMP-1 and VEGF in U-2 OS cells. Confocal microscopy revealed that deguelin reduced NF-κB p65, Rho A and ROCK-1 protein levels in cytosol. MMP-7, MMP-9 and Rho A mRNA levels were suppressed by deguelin. These in vitro results provide evidence that deguelin may have potential as a novel anti-cancer agent for the treatment of osteosarcoma and provides the rationale for in vivo studies in animal models. View Full-Text
Keywords: deguelin; U-2 OS human osteosarcoma cells; migration; invasion deguelin; U-2 OS human osteosarcoma cells; migration; invasion
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Shang, H.-S.; Chang, J.-B.; Lin, J.-H.; Lin, J.-P.; Hsu, S.-C.; Liu, C.-M.; Liu, J.-Y.; Wu, P.-P.; Lu, H.-F.; Au, M.-K.; Chung, J.-G. Deguelin Inhibits the Migration and Invasion of U-2 OS Human Osteosarcoma Cells via the Inhibition of Matrix Metalloproteinase-2/-9 in Vitro. Molecules 2014, 19, 16588-16608.

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