In order to detect intracellular NQO1 activity in MCF-7 aggregates as a cancer model, we present, in this study, a double-mediator system combined with large-scale integration (LSI)-based amperometric devices.
This approach is tested using large-scale experimental and structural perturbation analyses in over thirty mutations in three different proteins (cancer-associated NQO1, transthyretin related with amyloidosis and AGT linked to primary hyperoxaluria type I) and comprising five very common pathogenic mechanisms (loss-of-function and gain-of-toxic function aggregation, enzyme inactivation, protein mistargeting and accelerated degradation).
Human NAD(P)H:quinone oxidoreductase 1 (NQO1) is a multi-functional protein whose alteration is associated with cancer, Parkinson's and Alzheimer´s diseases.
This was associated with a marked decrease (50%) in the expression of detoxifying genes (NQO1 and GSTA1) with an increase in CYP1A1 mRNA expression, a cancer-activating gene.
Consequently, the correction of NQO1 misfolding by pharmacological chaperones is a viable strategy, which may be useful to treat cancer and some neurological conditions, targeting structural spots linked to specific disease-mechanisms.
Low NQO1 mRNA and protein levels were observed in the TP53 mutated subgroup compared to others tumors (p < .05) and in silico analyses of The Cancer Genome Atlas data further indicated that NQO1 mRNA levels were lower in serous compared to endometrioid copy-number high EC.
It was found that cytotoxic activities of the studied hybrids were increasing against the cell line with higher NQO1 protein level, like melanoma (C-32), breast (MCF-7) and lung (A-549) cancer.
Correlation of expression levels of these markers in the oral cancer cohort of The Cancer Genome Atlas (n = 313) with treatment outcome identified 54 genes (p < 0.05 or fold change >2) associated with disease recurrence, 8 genes (NQO1, UBE2C, EDNRB, FKBP4, STAT3, HOXA1, RIT1, AURKA) being significant with high fold change.
In this work, binding of anions to the FAD binding pocket of human NAD(P)H:quinone oxidoreductase 1 (NQO1), a flavoprotein associated with cancer due to a common polymorphism causing a P187S amino acid substitution, was investigated.
Here, we investigated this question and determined the molecular mechanisms underlying the roles of NQO1 in glycolysis reprogramming, proliferation, and metastasis breast cancer (BC) cells.
Therefore, the significant prognostic value of NQO1 in predicting outcome of cancer patients might be explained in part due to the functional contribution of NQO1-SIRT2 axis to mitotic stress.
Developing an effective method for detecting NQO1 activity with high sensitivity and selectivity in tumors holds a great potential for cancer diagnosis, treatment, and management.
The isolated compounds were evaluated for their potential to induce the cancer chemopreventive enzyme marker NAD(P)H quinonereductase 1 (NQO1) in murine Hepa-1c1c7 cell model.
The ethyl acetate extract of the peel induced quinone reductase 1 activity in Hepa1c1c7 cells, indicating that C. maxima exhibited cancer chemopreventive properties.
Tripartite prodrug 1, composed of an NAD(P)H:quinone oxidoreductase 1 (NQO1)-responsive trigger group, a self-immolative linker, and the active drug 5-fluorouracil (5-FU), was designed and synthesized for site-specific cancer therapy.
Deletions in GSTM1 and GSTT1, and single-nucleotide polymorphism (SNP) in NQO1 (rs1800655) have been investigated in cancer context, revealing conflicting results.
NAD(P)H quinone oxidoreductase 1 (NQO1)-dependent antitumor drugs such as β-lapachone (β-lap) are attractive candidates for cancer chemotherapy because several tumors exhibit higher expression of NQO1 than adjacent tissues.
On the basis of the different levels of NQO1 between cancer and normal cells, the catalytic property of NQO1 has recently been exploited to develop effective probes for cancer detection.