*The authors, Ya-Yin Chen, Hsu-Feng Lu, Jing-Gung Chung, and Jin-Biou Chang contributed equally to this work.
Bufalin inhibits migration and invasion in human hepatocellular carcinoma SK-Hep1 cells through the inhibitions of NF-kB and matrix metalloproteinase-2/-9-signaling pathways
Article first published online: 16 AUG 2013
Copyright © 2013 Wiley Periodicals, Inc.
How to Cite
Chen, Y.-Y., Lu, H.-F., Hsu, S.-C., Kuo, C.-L., Chang, S.-J., Lin, J.-J., Wu, P.-P., Liu, J.-Y., Lee, C.-H., Chung, J.-G. and Chang, J.-B. (2013), Bufalin inhibits migration and invasion in human hepatocellular carcinoma SK-Hep1 cells through the inhibitions of NF-kB and matrix metalloproteinase-2/-9-signaling pathways. Environ. Toxicol.. doi: 10.1002/tox.21896
- Article first published online: 16 AUG 2013
- Manuscript Accepted: 11 JUL 2013
- Manuscript Revised: 10 JUL 2013
- Manuscript Received: 7 SEP 2012
- China Medical University. Grant Number: CMU97-127
- matrix metalloproteinase-2/-9
Metastasis plays an important role in mortality of cancer patients. Migration and invasion are the major characteristics of tumor metastasis. The induction of matrix metalloproteinases (MMPs) such as MMP-2 and -9 are particularly important for the invasiveness of various cancer cells. Bufalin, a class of toxic steroids, was purified from the skin glands of Bufo gargarizans or Bufo melanostictus; it is known to inhibit proliferation of human cancer cells. In this study, we investigated the antiinvasive mechanisms of bufalin in the human hepatocellular cancer cell line SK-Hep1. Bufalin significantly reduced serum-induced cell invasion and migration. Furthermore, bufalin markedly inhibited MMP-2 and -9 activity, mRNA expression and protein levels in SK-Hep1 cells. Bufalin attenuated phosphoinisitide-3-kinase (PI3K) and phosphorylation of AKT which was associated with reduced levels of nuclear factor kappa B (NF-κB). Bufalin also suppressed protein levels of FAK and Rho A, VEGF, MEKK3, MKK7, and uPA and it diminished NF-κB translocation. Based on these observations, we propose that bufalin is acts as an antiinvasive agent by inhibiting MMP-2 and -9 and involving PI3K/AKT and NF-κB pathways. Bufalin is a potential therapeutic agent that may have efficacy in preventing the invasion and metastasis of malignant liver tumors. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.