NADPH oxidase5 (Nox5) is a novel Nox isoform which has recently been recognized as having important roles in the pathogenesis of coronary artery disease, acute myocardial infarction, fetal ventricular septal defect and cancer.
Aldo-keto reductases, known as AKR1C1-AKR1C4 enzymes, are pivotal to NADPH-dependent reduction, and their expression is highly associated with the progression of malignant cancers.
ET-1 has been reported to mediate superoxide formation in the vascular system via NADPH oxidase (NOX) and to regulate the actin cytoskeleton of cancer cell lines via the cofilin pathway.
Expression of most NADPH-producing dehydrogenase genes was not elevated in 34 cancer data sets except for IDH1 in glioma and thyroid cancer, indicating an association with the IDH1 mutation.
IDH1 and IDH2 are homodimeric enzymes that catalyze the conversion of isocitrate to α-ketoglutarate (α-KG) and concomitantly produce reduced NADPH from NADP(+) Mutations in the genes encoding IDH1 and IDH2 have recently been found in a variety of human cancers, most commonly glioma, acute myeloid leukemia (AML), chondrosarcoma, and intrahepatic cholangiocarcinoma.
In addition, recent studies reveal that targeting NADPH oxidases with NOXs inhibitors may impair tumor growth in vivo; indicating that these proteins may be useful targets in future clinical strategies to fight cancer.
Increased activity of NADPH oxidases has been implicated in various pathologies, including cardiovascular disease, neurological dysfunction, and cancer.
Sixty-three human lung tumors showed higher NADPH oxidase isoform 2 (NOX2) expression than normal lung tissues, which may contribute to high basal ROS in cancer and poor survival.
Some examples include the alanine-to-valine substitution at codon 222 (Ala222-->Val) [DNA: C-to-T substitution at nucleo-tide 677 (677C-->T)] in methylenetetrahydrofolate reductase (NADPH) and the cofactor FAD (in relation to cardiovascular disease, migraines, and rages), the Pro187-->Ser (DNA: 609C-->T) mutation in NAD(P):quinone oxidoreductase 1 [NAD(P)H dehy-drogenase (quinone)] and FAD (in relation to cancer), the Ala44-->Gly (DNA: 131C-->G) mutation in glucose-6-phosphate 1-dehydrogenase and NADP (in relation to favism and hemolytic anemia), and the Glu487-->Lys mutation (present in one-half of Asians) in aldehyde dehydrogenase (NAD + ) and NAD (in relation to alcohol intolerance, Alzheimer disease, and cancer).
The NADPH oxidase (NOX) family is overexpressed in many cancers and is associated with cancer cell proliferation and metastasis; however, little is known about the role of the NOX family in colorectal cancer (CRC).
The modulation of H<sub>2</sub> O<sub>2</sub> production by NADPH oxidase (Nox), on vascular endothelial growth factor (VEGF) stimulation, affects the redox signaling linked to cancer cell proliferation.
The oxidative stress management in cancer cells (i) was mainly controlled by GPx-1 and the main NADPH provider was Glc6PDH; and (ii) modeling indicated that NADPH supply was not a controlling step.
The pentose phosphate pathway (PPP) is thought to be upregulated in trauma (to produce excess NADPH) and in cancer (to provide ribose for nucleotide biosynthesis), but simple methods for detecting changes in flux through this pathway are not available.
These data suggest that lowering oxidative stress, possibly through the inhibition of NADPH oxidase, induces apoptosis in ovarian cancer cells and may serve as a potential target for cancer therapy.
This alteration has been interpreted as a cellular strategy to increase biomass during cancer, and one of its main factors is the availability of NADPH.
This model suggests that supplemental glycine may have utility for prevention and control of atherosclerosis, heart failure, angiogenesis associated with cancer or retinal disorders, and a range of inflammation-driven syndromes - including metabolic syndrome; and it might complement the suppression of NADPH oxidase activity achievable with phycocyanobilin-enriched spirulina extracts.