Myricetin / NOX4 Cancer Research Results

Myr, Myricetin: Click to Expand ⟱

Features:

Myricetin (MYR; 3,3′,4′,5,5′,7-hexahydroxyflavone) is a dietary flavonol polyphenol abundant in berries, tea, red wine, and some medicinal plants. Its dominant biology is redox-active modulation with context-dependent pro-oxidant capacity, ranking conceptually as:
(1) ROS modulation (scavenging at low dose; pro-oxidant at higher dose or with metal redox cycling),
(2) PI3K/Akt/mTOR and MAPK pathway inhibition,
(3) NF-κB suppression and inflammatory signaling control, and
(4) mitochondrial apoptosis induction (caspase activation, ΔΨm disruption).
Bioavailability is limited by low aqueous solubility and rapid conjugation (glucuronidation/sulfation); reported human plasma levels after dietary exposure are typically sub-micromolar (<1 µM), while many in-vitro cancer studies use 10–100 µM, often exceeding realistic systemic exposure. Clinical evidence remains preclinical-dominant; no robust RCT-grade anticancer efficacy established. Redox duality implies potential chemo-sensitization in oxidative tumors but also theoretical protection of normal tissue.

-Possible inhibitory effects on mammalian TrxRs (thioredoxin reductase)

Myricetin (MYR) — Cancer-Relevant Pathway Effects

Rank	Pathway / Axis	Cancer Cells (↑/↓/↔ + qualifiers)	Normal Cells (↑/↓/↔ + qualifiers)	TSF	Primary Effect	Notes / Interpretation
1	ROS Modulation	↑ ROS (high conc., pro-oxidant); ↓ ROS (low conc.)	↓ ROS (protective; dose-dependent)	P–R	Redox stress induction or buffering	Metal-chelating flavonol; can shift to pro-oxidant under tumor oxidative stress, enabling apoptosis.
2	PI3K/Akt/mTOR	↓ Akt phosphorylation (model-dependent)	↔ / mild inhibition	R–G	Anti-proliferative signaling	Common in breast, colon, and prostate cell models; often ≥10 µM required.
3	MAPK (ERK/JNK/p38)	↓ ERK; ↑ JNK/p38 (stress-activated; context)	↔ / adaptive stress response	R	Pro-apoptotic signaling shift	Promotes apoptotic cascades via stress kinase activation.
4	NF-κB	↓ NF-κB activation	↓ NF-κB (anti-inflammatory)	R–G	Anti-inflammatory modulation	May reduce tumor-promoting inflammation.
5	Mitochondrial Apoptosis (Caspase / ΔΨm)	↑ Bax; ↓ Bcl-2; ↑ caspase-3	↔ / protective at low dose	R–G	Intrinsic apoptosis activation	Frequently observed in leukemia and solid tumor models at supra-physiologic doses.
6	NRF2 Axis	↔ / mild ↑ (context-dependent)	↑ NRF2 (cytoprotection)	R–G	Adaptive antioxidant response	Less potent NRF2 activator than electrophilic isothiocyanates.
7	Ca²⁺ Signaling	↑ intracellular Ca²⁺ (mitochondrial stress; model-dependent)	↔	R	Apoptosis facilitation	Reported in some hepatoma and leukemia models.
8	Ferroptosis	↔ / potentially ↓ (iron-chelating)	↔	—	Lipid peroxidation modulation	Chelation may counter ferroptosis unless combined with pro-oxidant triggers.
9	Clinical Translation Constraint	Low oral bioavailability; plasma <1 µM; most anticancer studies use 10–100 µM		—	PK limitation	Conjugation and rapid metabolism limit systemic tumor exposure.

TSF Legend: P: 0–30 min R: 30 min–3 hr G: >3 hr

NOX4, NADPH oxidase 4: Click to Expand ⟱

Source:

Type:

NOX4 (NADPH oxidase 4) is a member of the NADPH oxidase (NOX) family of enzymes, which are responsible for generating reactive oxygen species (ROS) in various cell types. NOX4 is regulated by hypoxia, which can activate its expression and activity.
NOX4 (NADPH oxidase 4) is an enzyme that produces reactive oxygen species (ROS), particularly hydrogen peroxide (H₂O₂).
NOX4 is a cytoplasmic enzyme that catalyzes the transfer of electrons from NADPH to oxygen, resulting in the production of superoxide anion (O2-) and other ROS. NOX4 is expressed in a variety of tissues, including the kidney, lung, and vascular smooth muscle cells.
NOX4 is generally expressed in cancer.
In general, high NOX4 expression is associated with:
      Poor prognosis
      Increased tumor size
      Metastasis
      Resistance to chemotherapy and radiation therapy
      Poor response to treatment
Low NOX4 expression is associated with:
      Better prognosis
      Smaller tumor size
      Less metastasis
      Better response to chemotherapy and radiation therapy
      Better response to treatment

The combination of NOX4-driven ROS and available iron can lead to a synergistic increase in oxidative stress, setting the stage for ferroptotic cell death.

Scientific Papers found: Click to Expand⟱

1273-

Myr,

Myricetin Induces Ferroptosis and Inhibits Gastric Cancer Progression by Targeting NOX4

vitro+vivo,

GC,

Ferroptosis↑, MDA↑, Iron↑, GSH↓, NOX4↑, NRF2↓, GPx4↓,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Ferroptosis↑, 1, GPx4↓, 1, GSH↓, 1, Iron↑, 1, MDA↑, 1, NOX4↑, 1, NRF2↓, 1,

Cell Death ⓘ

Ferroptosis↑, 1,
Total Targets: 8

Pathway results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: NOX4, NADPH oxidase 4

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