Genistein from soy inhibits tumor invasion by suppressing multiple signal transduction pathways in human hepatocellular carcinoma cells

Monday, 20/01/2014  |   Uncategorized  |  no comments


Genistein (Gen) exhibits anti-mutagenic and anti-metastatic activities in hepatoma cell lines. Gen has suppressive effects on tumor growth and angiogenesis in nude mice. Gen suppresses the enzymatic activity of matrix metalloproteinase (MMP)-9; however, the mechanism underlying its anti-invasive activity on hepatocellular carcinoma (HCC) cells is unclear.

In this study, the possible mechanisms underlying Gen-mediated reduction of 12-O-Tetradecanoylphorbol-13-acetate (TPA)-induced cell invasion and inhibition of secreted and cytosolic MMP-9 production in human hepatoma cells (HepG2, Huh-7, and HA22T) and murine embryonic liver cells (BNL CL2) were investigated.
Gen suppressed MMP-9 transcription by inhibiting activator protein (AP)-1 and nuclear factor-kappa B (NF-kappaB) activity. Gen suppressed TPA-induced AP-1 activity through inhibitory phosphorylation of extracellular signal-related kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways, and TPA-stimulated inhibition of NF-kappaB nuclear translocation through IkappaB inhibitory signaling pathways. Moreover, Gen suppressed TPA-induced activation of ERK/phosphatidylinositol 3-kinase/Akt upstream of NF-kappaB and AP-1.

Gen and its inhibition of multiple signal transduction pathways can control the invasiveness and metastatic potential of HCC. 

Wang S-D, Chen B-C, Kao S-T, Liu C-J, Yeh C-C. BMC Complementary and Alternative Medicine 2014, 14:26  doi:10.1186/1472-6882-14-26

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