ENOX2 Cancer Research Results

ENOX2, NADH oxidases: Click to Expand ⟱
Source:
Type: "cancer-specific" cell surface marker
NADH oxidases (often referred to as tNOX/ENOX2)
tNOX stands for "tumor-associated NADH oxidase," and it is also known as ENOX2.
ENOX2 (Ecto-Nicotinamide Adenine Dinucleotide Oxidase Disulfide-Thiol Exchanger 2) is a protein that has drawn attention in the context of cancer.
ENOX2 is an enzyme found on the cell surface that exhibits NADH oxidase activity along with protein disulfide-thiol interchange activity.
Several studies have suggested that ENOX2 could be used as a biomarker for cancer diagnosis, prognosis, and monitoring.

NADH oxidases (often referred to as tNOX/ENOX2) and NADPH oxidase family members that have been implicated in redox regulation—detailing their expression in various cancers as well as correlations with prognosis.

– tNOX (also known as ENOX2) is a cancer‐specific cell surface NADH oxidase with a role in cellular growth regulation.
– This enzyme cycles between hydroquinone oxidase and protein disulfide-thiol interchange activities and is generally not expressed in normal cells.

• Expression in Cancer & Prognosis:
– ENOX2 is overexpressed in many solid tumors, including breast, prostate, lung, colon, and various hematologic malignancies.
– Elevated ENOX2 levels in patient sera or tumor samples have been correlated with aggressive tumor behavior and poor prognosis.
– The presence of ENOX2 activity often indicates an increased rate of cell proliferation and may predict recurrence after treatment.

ENOX2 is specifically expressed on the cell surface of many cancer cells and is involved in redox regulation and the control of cellular growth.
Because ENOX2 is predominantly expressed in tumors rather than normal tissues, it has been explored as a potential diagnostic and prognostic biomarker in oncology.

ENOX2 is frequently upregulated or more active in cancer cells.
By influencing the balance between NADH and NAD⁺, ENOX2 might shift the cellular redox state. An imbalance can lead to increased oxidative stress or changes in ROS signaling pathways.

Potential Effects of Inhibition (**** ROS increase ****)
When ENOX2 is inhibited, its NADH oxidase activity is reduced. This can lead to an altered cell redox state.
Some studies suggest that blocking ENOX2 activity in cancer cells disrupts their normal redox homeostasis. In certain cases, this disruption may result in the accumulation of NADH and/or an alteration in electron flow—conditions that can favor increased ROS production. Increased ROS can lead to oxidative stress that may trigger cell death (e.g., via apoptosis), which is one of the reasons researchers are interested in ENOX2 as a target for cancer therapy. While there is evidence that inhibiting ENOX2 can lead to an increase in ROS—contributing to oxidative stress and potentially cell death—this outcome is not universal.
Scientific Papers found: Click to Expand⟱
1517- CAP,    Capsaicin Inhibits Multiple Bladder Cancer Cell Phenotypes by Inhibiting Tumor-Associated NADH Oxidase (tNOX) and Sirtuin1 (SIRT1)
- in-vitro, Bladder, TSGH8301 - in-vitro, CRC, T24/HTB-9
ENOX2↓, capsaicin downregulates tNOX expression
TumCCA↑, Capsaicin Downregulates tNOX and Induces Cell Cycle Arrest at G1 Phase
ERK↓, inhibit the activation of ERK
p‑FAK↓,
p‑pax↓,
TumCMig↓,
EMT↓,
SIRT1↓, downregulation of sirtuin 1 (SIRT1) in these tNOX-knockdown cells
Dose∅, 100 and 200 μM effectively reduced tNOX expression in bladder cancer TSGH8301 and T24
ROS↑, capsaicin dose-dependently increased ROS generation
MMP↓,
Bcl-2↓,
Bak↑,
cl‑PARP↑,
Casp3↑,
SIRT1↓, 100 and 200 μM capsaicin decreased SIRT1 expression
ac‑P53↑, concurrently increased p53 acetylation
BIM↑, enhanced the expression level of Bim
p‑RB1↓, downregulation of phosphorylated Rb and cyclin D,
cycD1/CCND1↓,
Dose∅, Interestingly, cell migration was somewhat increased with 10 μM accompanied by up-regulation of tNOX expression
β-catenin/ZEB1↓,
N-cadherin↓,
E-cadherin↑,

637- EGCG,  CAP,    Cancer prevention trial of a synergistic mixture of green tea concentrate plus Capsicum (CAPSOL-T) in a random population of subjects ages 40-84
- Human, NA, NA
ENOX2↓, 94% of subjects subsequently tested negative for ENOX2 presence.

693- EGCG,  CAP,  Phen,    Metabolite modulation of HeLa cell response to ENOX2 inhibitors EGCG and phenoxodiol
- in-vitro, Cerv, HeLa
ENOX2↓, all 3 are enox2 inhibitors
TumCG↓, growth was inhibited by about 70% with 50 μM EGCG and 60% by 0.5 μM phenoxodiol

1514- EGCG,    Preferential inhibition by (-)-epigallocatechin-3-gallate of the cell surface NADH oxidase and growth of transformed cells in culture
- in-vitro, Cerv, HeLa - in-vitro, Nor, MCF10
selectivity↑, EGCg preferentially inhibited growth of HeLa and mammary adenocarcinoma cells compared with growth of mammary epithelial cells
*toxicity∅, Mammary epithelial cells recovered from EGCg treatment even at 50 mM
TumCG↓, growth of HeLa and mammary adenocarcinoma cells was inhibited by EGCg at concentrations as low as 1 mM. With repeated additions of 100 nM EGCg (every 2 hr during the day), growth was inhibited during the day but recovered during the night
NADHdeh?,
eff↑, Green tea infusions were approximately 10 times more effective than those of black tea and contained approximately 10 times more EGCg
ENOX2↓, EGCg inhibit the NADH oxidase(ENOX2) of plasma membrane vesicles from cancer cells and not that of normal cells,
Dose?, with repeated additions (twice daily) at 1 mM EGCg, the EGCg concentration achieving complete inhibition of tNOX in BT-20 cells, growth inhibition and apoptosis in BT-20 cells were achieved.

1515- EGCG,  Phen,    ENOX2_Inhibition_Triggers_Sphingolipid-Induced_Apoptosis_in_HeLa_Cells">Reciprocal Relationship Between Cytosolic NADH and ENOX2 Inhibition Triggers Sphingolipid-Induced Apoptosis in HeLa Cells
- in-vitro, Cerv, HeLa - in-vitro, Nor, MCF10 - in-vitro, BC, BT20
selectivity↑, ENOX2 INHIBITORS SLOW THE GROWTH OF HeLa CELLS AND INDUCE APOPTOSIS IN CANCER BUT NOT IN NON-CANCER CELLS
ENOX2↓,
NADH↑, INCREASED NADH RESULTING FROM ENOX2 CELL SURFACE INHIBITION INHIBITS PLASMA MEMBRANE-ASSOCIATED SPHINGOSINE KINASE (SK) AND LOWERS LEVELS OF PRO-SURVIVAL SPHINGOSINE-1-PHOSPHATE (S1P
SK↓, SK activity was decreased in response to 1.5 mM NADH
eff↑, Capsaicin added to block NADH oxidation by endo- genous ENOX2 was without effect when added alone but enhanced inhibition slightly when combined with 1.5 mM NADH
aSmase↑, SMase activity was stimulated by NADH


Showing Research Papers: 1 to 5 of 5

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 5

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

ENOX2↓, 5,   NADH↑, 1,   NADHdeh?, 1,   ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,  

Core Metabolism/Glycolysis ⓘ

SIRT1↓, 2,  

Cell Death ⓘ

aSmase↑, 1,   Bak↑, 1,   Bcl-2↓, 1,   BIM↑, 1,   Casp3↑, 1,   SK↓, 1,  

DNA Damage & Repair ⓘ

ac‑P53↑, 1,   cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 1,   p‑RB1↓, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 1,   ERK↓, 1,   TumCG↓, 2,  

Migration ⓘ

E-cadherin↑, 1,   p‑FAK↓, 1,   N-cadherin↓, 1,   p‑pax↓, 1,   TumCMig↓, 1,   β-catenin/ZEB1↓, 1,  

Drug Metabolism & Resistance ⓘ

Dose?, 1,   Dose∅, 2,   eff↑, 2,   selectivity↑, 2,  
Total Targets: 30

Pathway results for Effect on Normal Cells:


Functional Outcomes ⓘ

toxicity∅, 1,  
Total Targets: 1

Scientific Paper Hit Count for: ENOX2, NADH oxidases
4 EGCG (Epigallocatechin Gallate)
3 Capsaicin
2 PXD, phenoxodiol
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:%  Target#:822  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

 

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