Heat shock increases expression of NAD (P) H: quinone oxidoreductase (NQO1), mediator of β-lapachone cytotoxicity, by increasing NQO1 gene activity and via Hsp70-mediated stabilisation of NQO1 protein

摘要: NAD(P)H:quinone oxidoreductase (NQO1) mediates cell death caused by the novel anti‐cancer drug β‐lapachone (β‐lap). Therefore, β‐lap sensitivity of cells is positively related to the level of cellular NQO1. Heat shock up‐regulates NQO1 expression in cancer cells, thereby enhancing the clonogenic cell death caused by β‐lap. The mechanisms by which heat shock elevates NQO1 expression were investigated in the present study using human A549 lung cancer cells and human MDA‐MB‐231 breast cancer cells. When MDA‐MB‐231(NQO1+) cells stably transfected with NQO1 were heated at 42°C for 1 h the expression of NQO1 and the sensitivity of the cells to β‐lap progressively increased during the 24–48 h post‐heating period. Heating increased NQO1 transcription by cis‐acting elements such as xenobiotic response element and antioxidant response element located in the NQO1 gene promoter region …