Journal
CHEMICO-BIOLOGICAL INTERACTIONS
Volume 235, Issue -, Pages 1-9Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2015.04.003
Keywords
ERK; JNK; PI3K; AKT; NF-kappa B; AP-1
Funding
- Buddhist Dalin Tzu Chi General Hospital, Taiwan [DTCRD98(2)-12]
- China Medical University under the Aim for Top University Plan of the Ministry of Education, Taiwan
- Ministry of Science and Technology [NSC102-2320-B-182-018-MY3]
- National Health Research Institutes, Taiwan [NHRI-EX101-10124SC, NHRI-EX102-10124SC, NHRI-EX103-10124SC]
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Naringenin, a common dietary flavonoid abundantly present in fruits and vegetables, is believed to possess strong anti-proliferative properties and the ability to induce apoptosis in hepatoma cell lines. However, there are no reports describing its effects on the invasion and metastasis of hepatoma cell lines, and the detailed molecular mechanisms of its effects are still unclear. In this study, we investigated the mechanisms underlying naringenin-mediated inhibition 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). Naringenin suppressed MMP-9 transcription by inhibiting activator protein (AP)-1 and nuclear factor-kappa B (NF-kappa B) activity. It suppressed TPA-induced AP-1 activity through inhibiting the phosphorylation of the extracellular signal-related kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways, and it suppressed TPA-induced inhibition of NF-kappa B nuclear translocation through I kappa B. Additionally, it suppressed TPA-induced activation of ERK/phosphatidylinositol 3-kinase/Akt upstream of NF-kappa B and AP-1. These data suggest that naringenin suppresses the invasiveness and metastatic potential of hepatocellular carcinoma (HCC) by inhibiting multiple signal transduction pathways. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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