Get access

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

Authors

  • Fu-Shin Chueh,

    1. Department of Health and Nutrition Biotechnology, Asia University, Taichung 413, Taiwan
    Search for more papers by this author
  • Ya-Yin Chen,

    1. Department of Chinese-Western Medicine Integration, Chung Shan Medical University Hospital, Taichung 402, Taiwan
    2. School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
    Search for more papers by this author
  • An-Cheng Huang,

    1. Department of Nursing, St. Mary's Medicine Nursing and Management College, Yilan 266, Taiwan
    Search for more papers by this author
  • Heng-Chien Ho,

    1. Department of Biochemistry, China Medical University, Taichung 404, Taiwan
    Search for more papers by this author
  • Ching-Lung Liao,

    1. Graduate Institute of Chinese Medicine, China Medical University, Taichung 404, Taiwan
    Search for more papers by this author
  • Jai-Sing Yang,

    1. Department of Pharmacology, China Medical University, Taichung 404, Taiwan
    Search for more papers by this author
  • Chao-Lin Kuo,

    Corresponding author
    1. School of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 404, Taiwan
    • School of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 404, TaiwanDepartment of Biological Science and Technology, China Medical University, Taichung 404, Taiwan. E-mail: clkuo@mail.cmu.edu.tw jgchung@mail.cmu.edu.tw

    Search for more papers by this author
    • These authors contributed equally to this work.

  • Jing-Gung Chung

    Corresponding author
    1. Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan
    2. Department of Biotechnology, Asia University, Taichung 413, Taiwan
    • School of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 404, TaiwanDepartment of Biological Science and Technology, China Medical University, Taichung 404, Taiwan. E-mail: clkuo@mail.cmu.edu.tw jgchung@mail.cmu.edu.tw

    Search for more papers by this author
    • These authors contributed equally to this work.


Abstract

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.

Ancillary