Department of Biochemistry, College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China.
Biochem Biophys Res Commun. 2012 Feb 24;418(4):647-51. doi: 10.1016/j.bbrc.2012.01.068. Epub 2012 Jan 24.
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.
脂质代谢酶及其代谢物调节癌细胞中转录因子的问题尚未完全阐明。在本研究中，我们首次报道脂质代谢酶 5-脂氧合酶（5-LOX）及其代谢产物白三烯 B4（LTB4）能够激活肝癌细胞中的核因子-κB（NF-κB）。我们发现，MK886（5-LOX 抑制剂）处理或敲低 5-LOX 能够下调肝癌 HepG2 或 H7402 细胞中 NF-κB p65 的 mRNA 水平表达，并降低细胞质中抑制剂 κBα（IκBα）的磷酸化水平，导致核 NF-κB p65 水平降低。这些结果在 HepG2 细胞的免疫荧光染色中得到了证实。此外，上述处理能够降低细胞中 NF-κB 的转录活性。5-LOX 的代谢产物之一 LTB4 以剂量依赖的方式负责 5-LOX 激活的 NF-κB。因此，我们得出结论，脂质代谢酶 5-LOX 及其代谢产物 LTB4 能够激活肝癌细胞中的转录因子 NF-κB。我们的发现为脂质代谢在癌症中激活转录因子的意义提供了新的见解。
