title: Deguelin inhibits the migration and invasion of U-2 OS human osteosarcoma cells via the inhibition of matrix metalloproteinase-2/-9 in vitro.
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.
authors.affiliation: Department of Pathology, National Defense Medical Center, Division of Clinical Pathology, Tri-Service General Hospital, Taipei 114, Taiwan.
authors.forename: Hung-Sheng
authors.initials: HS
authors.lastname: Shang
authors.affiliation: Department of Pathology, National Defense Medical Center, Division of Clinical Pathology, Tri-Service General Hospital, Taipei 114, Taiwan.
authors.forename: Jin-Biou
authors.initials: JB
authors.lastname: Chang
authors.affiliation: Department of Biological Science and Technology, China Medical University, No 91, Hsueh-Shih Road, Taichung 404, Taiwan.
authors.forename: Ju-Hwa
authors.initials: JH
authors.lastname: Lin
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung 404, Taiwan.
authors.forename: Jing-Pin
authors.initials: JP
authors.lastname: Lin
authors.affiliation: Department of Biological Science and Technology, China Medical University, No 91, Hsueh-Shih Road, Taichung 404, Taiwan.
authors.forename: Shu-Chun
authors.initials: SC
authors.lastname: Hsu
authors.affiliation: Department of Research and Education, Cheng-Hsin General Hospital, No.45, Cheng Hsin St., Pai-Tou, Taipei 112, Taiwan.
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Liu
authors.affiliation: Department of Clinical Pathology, Cheng-Hsin General Hospital, Taipei 112, Taiwan.
authors.forename: Jia-You
authors.initials: JY
authors.lastname: Liu
authors.affiliation: School of Pharmacy, China Medical University, Taichung 404, Taiwan.
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: Wu
authors.affiliation: Department of Clinical Pathology, Cheng-Hsin General Hospital, Taipei 112, Taiwan.
authors.forename: Hsu-Feng
authors.initials: HF
authors.lastname: Lu
authors.affiliation: Department of Orthopedic Surgery, Cheng-Hsin General Hospital, Taipei 112, Taiwan. ch6200@chgh.org.tw.
authors.forename: Man-Kuan
authors.initials: MK
authors.lastname: Au
authors.affiliation: Department of Biological Science and Technology, China Medical University, No 91, Hsueh-Shih Road, Taichung 404, Taiwan. jgchung@mail.cmu.edu.tw.
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
mesh_terms: D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology; D012402:Rotenone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D012402:Rotenone; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C107676:deguelin