These authors contributed equally to this work.
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
Article first published online: 16 SEP 2011
Copyright © 2011 Wiley Periodicals, Inc.
Volume 29, Issue 1, pages 21–29, January 2014
How to Cite
Chueh, F.-S., Chen, Y.-Y., Huang, A.-C., Ho, H.-C., Liao, C.-L., Yang, J.-S., Kuo, C.-L. and Chung, J.-G. (2014), 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. Environ. Toxicol., 29: 21–29. doi: 10.1002/tox.20769
- Issue published online: 16 DEC 2013
- Article first published online: 16 SEP 2011
- Manuscript Accepted: 18 AUG 2011
- Manuscript Revised: 16 AUG 2011
- Manuscript Received: 7 MAY 2011
- China Medical University, Taichung, Taiwan. Grant Number: CMU99-ASIA-22
- migration and invasion;
- human osteosarcoma U-2 OS cells;
- matrix metalloproteinases;
- traditional Chinese medicine
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.