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Bufalin‐inhibited migration and invasion in human osteosarcoma U‐2 OS cells is carried out by suppression of the matrix metalloproteinase‐2, ERK, and JNK signaling pathways
Author(s) -
Chueh FuShin,
Chen YaYin,
Huang AnCheng,
Ho HengChien,
Liao ChingLung,
Yang JaiSing,
Kuo ChaoLin,
Chung JingGung
Publication year - 2014
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.20769
Subject(s) - bufalin , kinase , mapk/erk pathway , p38 mitogen activated protein kinases , matrix metalloproteinase , signal transduction , chemistry , microbiology and biotechnology , cell migration , cell cycle , cell growth , blot , biology , apoptosis , cell , biochemistry , gene
Bufalin has been shown to exhibit multiple pharmacological activities, including induction of apoptosis in many types of cancer cell lines. Osteosarcoma is a type of cancer which is difficult to treat and the purpose of this study was to investigate the effects of bufalin on the migration and invasion of human osteosarcoma U‐2 OS cells. The wound healing assay and Boyden chamber transwell assay were used for examining the migration of U‐2 OS cells. Western blotting and gelatin zymography assays were used for theexpression and activities of metalloproteinase (MMP)‐2, MMP‐7 or MMP‐9 levels. Western blotting analysis also was used for measuring the levels of growth factor receptor‐bound protein 2 (GRB2), son of sevenless homolog 1 (SOS1), c‐Jun N‐terminal kinases 1/2 (JNK1/2), extracellular signal‐regulated kinase 1/2 (ERK1/2), and p38 in bufalin‐treated U‐2 OS cells. Bufalin inhibited the cell migration and invasion of U‐2 OS cells in vitro . Moreover, bufalin reduced MMP‐2 and MMP‐9 enzyme activities of U‐2 OS cells. Bufalin also suppressed the protein level of MMP‐2 and reduced the levels of mitogen‐activated protein kinases (MAPKs) such as JNK1/2 and ERK1/2 signals in U‐2 OS cells. Our results suggest that signaling pathways for bufalin‐inhibited migration and invasion of U‐2 OS cells might be mediated through blocking MAPK signaling and resulting in the inhibition of MMP‐2. Bufalin could be a useful agent to develop as a novel antitumor agent by virtue of its ability to inhibit tumor cell migration and invasion. © 2011 Wiley Periodicals, Inc. Environ Toxicol 29: 21–29, 2014.