Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.5.2 (NQO1)
 6,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DT-diaphorase (DTD) is an obligate two-electron reductase which bioactivates chemotherapeutic quinones. DTD levels are elevated in a number of tumour types, including non-small cell lung carcinoma, colorectal carcinoma, liver cancers and breast carcinomas, when compared to the surrounding normal tissue. The differential in DTD between tumour and normal tissue should allow targeted activation of chemotherapeutic quinones in the tumour whilst minimising normal tissue toxicity. The prototypical bioreductive drug is Mitomycin C (MMC) which is widely used in clinical practice. However, MMC is actually a relatively poor substrate for DTD and its metabolism is pH-dependent. Other bioreductive drugs have failed because of poor solubility and inability to surpass other agents in use. RH1, a novel diaziridinylbenzoquinone, is a more efficient substrate for DTD. It has been demonstrated to have anti-tumour effects both in vitro and in vivo and demonstrates a relationship between DTD expression levels and drug response. RH1 has recently entered a phase I clinical trial in solid tumours under the auspices of Cancer Research UK. Recent work has demonstrated that DTD is present in the nucleus and is associated with both p53 and the heat shock protein, HSP-70. Furthermore, DTD is inducible by several non-toxic compounds and therefore much interest has focussed on increasing the differential in DTD levels between tumour and normal tissues.
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PMID:DT-diaphorase: a target for new anticancer drugs. 1524 76

Hemp seed has been used as a traditional oriental medicine and health food in China for centuries. Polysaccharides from hemp seed (HSP) exhibit important properties of intestinal protection, but there are limited data on the specific underlying mechanism. The primary objective of this study was to investigate the protective effect of HSP on intestinal oxidative damage induced by cyclophosphamide (Cy) in mice. The results showed that pretreatment with HSP significantly increased the average daily gain, thymus index, spleen index, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activity in serum and ileal homogenate and significantly reduced malondialdehyde (MDA) content in ileal homogenate. In addition, the expression levels of SOD, GSH-Px, Nrf2, heme oxidase-1 (HO-1), and quinoneoxidoreductase-1 (NQO1) mRNA in ileal homogenate were significantly increased. Western blot results showed that HSP significantly upregulated the expression of Nrf2 protein and downregulated the expression of Keap1 protein in the ileum. Collectively, our findings indicated that HSP had protective effects on intestinal oxidative damage induced by Cy in mice, and its mechanism might be related to the activation of Nrf2-Keap1 signaling pathway.
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PMID:Polysaccharides from Hemp Seed Protect against Cyclophosphamide-Induced Intestinal Oxidative Damage via Nrf2-Keap1 Signaling Pathway in Mice. 3290 23