title: Hydroquinone stimulates cell invasion through activator protein-1-dependent induction of MMP-9 in HepG2 human hepatoma cells.
abstract: Hydroquinone (HQ) is a well-known environmental carcinogen and exposure of humans to HQ can also occur through plant foods, cosmetics, and tobacco products. Although liver is a major organ metabolizing HQ and susceptible to its toxicity, role of HQ in metastatic progression of human hepatocellular carcinoma (HCC) remains unclear. In this study, we examined the effect of HQ on the invasion of HCC cells and its underlying molecular mechanisms. HQ strongly induced matrix metalloproteinase-9 (MMP-9) expression and secretion in HepG2 human hepatoma cells, which were well correlated with increased cell invasion. Mechanistic studies further demonstrated that HQ induced transcriptional activity of MMP-9 gene by activating activator protein-1 (AP-1), the well-known key element mediating MMP-9 gene expression, via MAP kinase (MAPK) signaling pathways. These results suggest that HQ may promote metastatic progression of HCC, although data on in vivo hydroquinone exposure and risk for HCC are contradictory.
authors.affiliation: Department of Food Science and Technology, Keimyung University, Daegu 42601, Republic of Korea.
authors.forename: Mi-Hee
authors.initials: MH
authors.lastname: Yu
authors.affiliation: Department of Food Science and Technology, Keimyung University, Daegu 42601, Republic of Korea; CK-1, Food and Biotechnology Expert Training Program, Keimyung University, Daegu 42601, Republic of Korea. Electronic address: synglee@kmu.ac.kr.
authors.forename: Syng-Ook
authors.initials: SO
authors.lastname: Lee
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D004790:Enzyme Induction; D056945:Hep G2 Cells; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*
chemical_list: D006873:Hydroquinones; D018808:Transcription Factor AP-1; D020780:Matrix Metalloproteinase 9; C031927:hydroquinone
keywords: AP-1; HepG2 human hepatoma cells; Hydroquinone; Invasion; MMP-9