Deguelin Inhibits the Migration and Invasion of U-2 OS Human Osteosarcoma Cells via the Inhibition of Matrix Metalloproteinase-2/-9 in Vitro
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 anti...
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| Format: | Article |
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MDPI AG
2014-10-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/19/10/16588 |
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| author | Hung-Sheng Shang Jin-Biou Chang Ju-Hwa Lin Jing-Pin Lin Shu-Chun Hsu Chi-Ming Liu Jia-You Liu Ping-Ping Wu Hsu-Feng Lu Man-Kuan Au Jing-Gung Chung |
| author_facet | Hung-Sheng Shang Jin-Biou Chang Ju-Hwa Lin Jing-Pin Lin Shu-Chun Hsu Chi-Ming Liu Jia-You Liu Ping-Ping Wu Hsu-Feng Lu Man-Kuan Au Jing-Gung Chung |
| author_sort | Hung-Sheng Shang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T18:39:46Z |
| format | Article |
| id | doaj.art-7cf2a9acaf9c44789e179172a96dbcb6 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-12T18:39:46Z |
| publishDate | 2014-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-7cf2a9acaf9c44789e179172a96dbcb62022-12-22T03:20:49ZengMDPI AGMolecules1420-30492014-10-011910165881660810.3390/molecules191016588molecules191016588Deguelin Inhibits the Migration and Invasion of U-2 OS Human Osteosarcoma Cells via the Inhibition of Matrix Metalloproteinase-2/-9 in VitroHung-Sheng Shang0Jin-Biou Chang1Ju-Hwa Lin2Jing-Pin Lin3Shu-Chun Hsu4Chi-Ming Liu5Jia-You Liu6Ping-Ping Wu7Hsu-Feng Lu8Man-Kuan Au9Jing-Gung Chung10Department of Pathology, National Defense Medical Center, Division of Clinical Pathology, Tri-Service General Hospital, Taipei 114, TaiwanDepartment of Pathology, National Defense Medical Center, Division of Clinical Pathology, Tri-Service General Hospital, Taipei 114, TaiwanDepartment of Biological Science and Technology, China Medical University, No 91, Hsueh-Shih Road, Taichung 404, TaiwanSchool of Chinese Medicine, China Medical University, Taichung 404, TaiwanDepartment of Biological Science and Technology, China Medical University, No 91, Hsueh-Shih Road, Taichung 404, TaiwanDepartment of Research and Education, Cheng-Hsin General Hospital, No.45, Cheng Hsin St., Pai-Tou, Taipei 112, TaiwanDepartment of Clinical Pathology, Cheng-Hsin General Hospital, Taipei 112, TaiwanSchool of Pharmacy, China Medical University, Taichung 404, TaiwanDepartment of Clinical Pathology, Cheng-Hsin General Hospital, Taipei 112, TaiwanDepartment of Orthopedic Surgery, Cheng-Hsin General Hospital, Taipei 112, TaiwanDepartment of Biological Science and Technology, China Medical University, No 91, Hsueh-Shih Road, Taichung 404, TaiwanOsteosarcoma 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.http://www.mdpi.com/1420-3049/19/10/16588deguelinU-2 OS human osteosarcoma cellsmigrationinvasion |
| spellingShingle | Hung-Sheng Shang Jin-Biou Chang Ju-Hwa Lin Jing-Pin Lin Shu-Chun Hsu Chi-Ming Liu Jia-You Liu Ping-Ping Wu Hsu-Feng Lu Man-Kuan Au Jing-Gung Chung Deguelin Inhibits the Migration and Invasion of U-2 OS Human Osteosarcoma Cells via the Inhibition of Matrix Metalloproteinase-2/-9 in Vitro Molecules deguelin U-2 OS human osteosarcoma cells migration invasion |
| title | Deguelin Inhibits the Migration and Invasion of U-2 OS Human Osteosarcoma Cells via the Inhibition of Matrix Metalloproteinase-2/-9 in Vitro |
| title_full | Deguelin Inhibits the Migration and Invasion of U-2 OS Human Osteosarcoma Cells via the Inhibition of Matrix Metalloproteinase-2/-9 in Vitro |
| title_fullStr | Deguelin Inhibits the Migration and Invasion of U-2 OS Human Osteosarcoma Cells via the Inhibition of Matrix Metalloproteinase-2/-9 in Vitro |
| title_full_unstemmed | Deguelin Inhibits the Migration and Invasion of U-2 OS Human Osteosarcoma Cells via the Inhibition of Matrix Metalloproteinase-2/-9 in Vitro |
| title_short | Deguelin Inhibits the Migration and Invasion of U-2 OS Human Osteosarcoma Cells via the Inhibition of Matrix Metalloproteinase-2/-9 in Vitro |
| title_sort | deguelin inhibits the migration and invasion of u 2 os human osteosarcoma cells via the inhibition of matrix metalloproteinase 2 9 in vitro |
| topic | deguelin U-2 OS human osteosarcoma cells migration invasion |
| url | http://www.mdpi.com/1420-3049/19/10/16588 |
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