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Medication: Nanoparticles for Imaging and Drug Delivery
Published in Harry F. Tibbals, Medical Nanotechnology and Nanomedicine, 2017
Dr. David Boothman and his colleagues at the University of Texas Southwestern Medical Center, Dallas, Texas found that 8-lapachone interacts with an enzyme called NQO1 (NAD(P)H:quinone oxidoreductase), which is present at high levels in certain types of solid cancer tumors. In tumors, the compound is metabolized by NQO1 and produces cell death but does not initiate apoptosis in noncancerous tissues, since they normally do not express this enzyme. In the tumor cells, β-lapachone induces a novel apop-totic pathway dependent on NQO1, which reduces β-lapachone to an unstable hydroquinone that rapidly undergoes a two-step oxidation back to the parent compound, perpetuating a self-sustaining redox cycle. A deficiency or inhibition of NQO1, such as is the case in normal cells, protects them from the effects of β-lapachone—but when β-lapachone interacts with NQO1 in the tumor cell, the cell kills itself [385].
Protective effects of natural compounds against paraquat-induced pulmonary toxicity: the role of the Nrf2/ARE signaling pathway
Published in International Journal of Environmental Health Research, 2023
Hasan Badibostan, Nastaran Eizadi-Mood, A. Wallace Hayes, Gholamreza Karimi
Alpha lipoic acid (LA), a naturally occurring organosulfur compound with potent antioxidant properties, is present in plants, animals, and humans (Szeląg et al. 2012). The ameliorative effect of this active component was observed in PQ-induced oxidative injuries in bronchial epithelial cells grown in culture (Iles et al. 2005). LA reduced the elevated levels of ROS, LDH, and malondialdehyde (MDA) in BEAS-2B cells. LA up-regulated the expression of Nrf2 and its downstream targets including HO-1, CAT, GPXs, and NQO1 in PQ-treated cells. The cytoprotective effect of HO-1 in pulmonary cells has also been reported (Iles et al. 2005). Due to its catalytic activity, NQO1 protects cells against the harmful effects of quinones and their metabolic precursors (Kim et al. 2013). The Keap1/Nrf2/ARE complex controls the expression of NQO1. Dinkova-Kostova and Talalay have demonstrated that induction of NQO1 is correlated with the reduction of susceptibilities to oxidative damage (Dinkova-Kostova and Talalay 2010).
DFT study on Fe and N decorated graphene as the drug delivery system for β-lapachone anticancer drug
Published in Molecular Physics, 2022
β-lapachone (β-lap), a simple plant product, had been reported with high performance in cancer treatment which gains lots of attention [11–13]. Compared to other chemotherapeutic drugs, β-lap presents high selectivity against prostate cancer cells overexpressing the NAD(P)H: quinone oxidoreductase-1 (NQO1). As we all know, NQO1 is overexpressed (up to 20-fold) in various tumor cells such as lung, prostate, pancreas, and breast cancers. This feature makes cancerous cells an ideal target for anticancer drugs while protecting healthy cells. However, despite a good sense of the NQO1 contained cancer cells, β-lap shows a low solubility in water (0.038 mg/mL) which hinders its clinical translation by traditional routes [3]. With this problem, exploring an efficient and biocompatible nano-carrier for β-lap is a critical solution to increase the drug bioavailability.
The expression of Phase II drug-metabolizing enzymes in human B-lymphoblastoid TK6 cells
Published in Journal of Environmental Science and Health, Part C, 2022
Xilin Li, Yuxi Li, Kylie G. Ning, Si Chen, Lei Guo, Jessica A. Bonzo, Nan Mei
The NQO gene family consists of two members, NQO1 and NQO2. Both of them encode cytosolic flavoenzymes that catalyze the reduction of quinone to hydroquinone, which is considered an antioxidation and detoxification process.32 For example, NQO1 deficiency leads to increased genotoxicity (as measured by the micronucleus assay) of benzene in mice.33 However, such a reduction is not always protective in cells. It is well documented that NQO1 catalyzes the bioreductive activation of mitomycin C, generating leucomitomycin C that causes DNA interstrand crosslinking.34 We found the mRNA of NQO1 was highly expressed in TK6 cells – the expression value ranked the 3rd highest among the 84 Phase II enzymes investigated (Table 1). NQO1 protein was also identified in TK6 cells, although the band intensity was weak due to an extremely high level of NQO1 expressed in HepG2 cells (Figure 1A). Notably, the gene expression level of NQO1 in HepG2 cells was significantly higher than that in TK6 cells and PHHs, respectively (Table 1). PHHs had no detectable protein level of NQO1, and the trend was consistent with the gene expression level (Figure 1A). Since many genotoxicants, especially dietary supplements, exert their DNA-damaging effects via oxidative stress, HepG2 cells may be less sensitive in detecting the genotoxicity of these agents due to a relatively high level of NQO1.