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Abstract Title:

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.

Abstract Source:

Environ Toxicol. 2015 Jan ;30(1):74-82. Epub 2013 Aug 16. PMID: 23949904

Abstract Author(s):

Ya-Yin Chen, Hsu-Feng Lu, Shu-Chun Hsu, Chao-Lin Kuo, Shu-Jen Chang, Jen-Jyh Lin, Ping-Ping Wu, Jia-You Liu, Ching-Hsiao Lee, Jing-Gung Chung, Jin-Biou Chang

Article Affiliation:

Ya-Yin Chen

Abstract:

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 apotential therapeutic agent that may have efficacy in preventing the invasion and metastasis of malignant liver tumors.

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Sayer Ji
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