title: Lipid metabolism enzyme 5-LOX and its metabolite LTB4 are capable of activating transcription factor NF-κB in hepatoma cells.
abstract: The issue that lipid metabolism enzyme and its metabolites regulate transcription factors in cancer cell is not fully understood. In this study, we first report that the lipid metabolism enzyme 5-Lipoxygenase (5-LOX) and its metabolite leukotriene B4 (LTB4) are capable of activating nuclear factor-κB (NF-κB) in hepatoma cells. We found that the treatment of MK886 (an inhibitor of 5-LOX) or knockdown of 5-LOX was able to downregulate the expression of NF-κB p65 at the mRNA level and decreased the phosphorylation level of inhibitor κBα (IκBα) in the cytoplasm of hepatoma HepG2 or H7402 cells, which resulted in the decrease of the level of nuclear NF-κB p65. These were confirmed by immunofluorescence staining in HepG2 cell. Moreover, the above treatments were able to decrease the transcriptional activity of NF-κB in the cells. The LTB4, one of metabolites of 5-LOX, is responsible for 5-LOX-activated NF-κB in a dose-dependent manner. Thus, we conclude that the lipid metabolism enzyme 5-LOX and its metabolite LTB4 are capable of activating transcription factor NF-κB in hepatoma cells. Our finding provides new insight into the significance of lipid metabolism in activation of transcription factors in cancer.
authors.affiliation: Department of Biochemistry, College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.forename: Wenhui
authors.initials: W
authors.lastname: Wang
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
authors.forename: Lihong
authors.initials: L
authors.lastname: Ye
mesh_terms: D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D007975:Leukotriene B4 / Q000378:metabolism*; D050356:Lipid Metabolism / Q000187:drug effects; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000819:agonists* / Q000378:metabolism; D051996:Transcription Factor RelA / Q000819:agonists / Q000378:metabolism; D014158:Transcription, Genetic; D002722:Chlorobenzenes
chemical_list: D001094:Arachidonate 5-Lipoxygenase; D051550:I-kappa B Kinase; D007211:Indoles; D007975:Leukotriene B4; D016859:Lipoxygenase Inhibitors; D016328:NF-kappa B; D051996:Transcription Factor RelA; C060893:MK-886; D002722:Chlorobenzenes