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BACKGROUND AND PURPOSE 2,5-diaziridinyl-3-(hydroxymethyl)-6-methyl-1,4-benzoquinone (RH1) is a bioreductive agent that is activated by the two-electron reductase NAD(P)H quinone oxidoreductase 1 (NQO1). Although the cytotoxic efficacy of RH1 against tumours has been studied extensively, the molecular mechanisms underlying this anti-cancer activity have not(More)
BACKGROUND β-Lapachone (β-lap) is a bioreductive agent that is activated by the two-electron reductase NAD(P)H quinone oxidoreductase 1 (NQO1). Although β-lap has been reported to induce apoptosis in various cancer types in an NQO1-dependent manner, the signaling pathways by which β-lap causes apoptosis are poorly understood. METHODOLOGY/PRINCIPAL(More)
Histone deacetylase (HDAC) plays an important role in cancer onset and progression. Therefore, inhibition of HDAC offers potential as an effective cancer treatment regimen. CG200745, (E)-N(1)-(3-(dimethylamino)propyl)-N(8)-hydroxy-2-((naphthalene-1-loxy)methyl)oct-2-enediamide, is a novel HDAC inhibitor presently undergoing a phase I clinical trial.(More)
NAD(P)H:quinone oxidoreductase (NQO1) has been reported to play an important role in cell death caused by beta-lapachone (beta-lap), 3,4-dihydro-22,2-dimethyl-2H-naphthol[1,22b]pyran-5,6-dione. This study investigated whether cisplatin (cis-diamminedichloroplatinum) sensitizes cancer cells to beta-lap by upregulating NQO1. The cytotoxicity of cisplatin and(More)
NAD(P)H quinone oxidoreductase (NQO1), an obligatory two-electron reductase, is a ubiquitous cytosolic enzyme that catalyzes the reduction of quinone substrates. The NQO1- mediated two-electron reduction of quinones can be either chemoprotection/detoxification or a chemotherapeutic response, depending on the target quinones. When toxic quinones are reduced(More)
BACKGROUND β-lapachone (β-lap), has been known to cause NQO1-dependnet death in cancer cells and sensitize cancer cells to ionizing radiation (IR). We investigated the mechanisms underlying the radiosensitization caused by β-lap. METHODOLOGY/PRINCIPAL FINDINGS β-lap enhanced the effect of IR to cause clonogenic cells in NQO1(+)-MDA-MB-231 cells but not in(More)
Metformin, the most widely prescribed drug for treatment of type 2 diabetes, has been shown to exert significant anticancer effects. Hyperthermia has been known to kill cancer cells and enhance the efficacy of various anti-cancer drugs and radiotherapy. We investigated the combined effects of metformin and hyperthermia against MCF-7 and MDA-MB-231 human(More)
NAD(P)H:quinone oxidoreductase (NQO1) mediates cell death caused by the novel anti-cancer drug beta-lapachone (beta-lap). Therefore, beta-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 beta-lap. The mechanisms by(More)
We developed a novel method for harvesting endothelial cells from blood vessels of freshly obtained cancer and adjacent normal tissue of human breast, and compared the response of the cancer-derived endothelial cells (CECs) and normal tissue-derived endothelial cells (NECs) to ionizing radiation. In brief, when tissues were embedded in Matrigel and cultured(More)
Aneuploidy is the most common characteristic of human cancer cells. It also causes genomic instability, which is involved in the initiation of cancer development. Various lines of evidence indicate that nicotinamide adenine dinucleotide(P)H quinone oxidoreductase 1 (NQO1) plays an important role in cancer prevention, but the molecular mechanisms underlying(More)