Myricetin / IDO1 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
IDO1, indoleamine 2, 3-dioxygenase 1: Click to Expand ⟱
Source:
Type:
IDO1 (Indoleamine 2,3-dioxygenase 1) is an enzyme involved in the catabolism of the essential amino acid tryptophan through the kynurenine pathway. Its activity can modulate the tumor immune microenvironment, and its expression has been associated with immune tolerance in various cancers.

– IDO1 is frequently overexpressed in a wide range of cancers, including melanoma, lung, breast, colorectal, and ovarian cancers.
– Elevated IDO1 expression in tumors is often found both in tumor cells and in immune cells within the tumor microenvironment.
– Inhibitors of IDO1 aim to restore tryptophan levels in the tumor microenvironment and reinvigorate T-cell mediated anti-tumor responses.

IDO1 inhibitory effects:
-Epigallocatechin Gallate (EGCG)
-Curcumin
-Resveratrol
-Berberine
-4‑phenylimidazole (research drug, small molecule)

IDO1 is an immunomodulatory enzyme that catabolizes tryptophan into kynurenine and related metabolites, thereby influencing the local immune environment.
Its expression is found in various cell types, including tumor cells, antigen-presenting cells, and stromal cells.
• IDO1 activity results in local tryptophan depletion and accumulation of immunosuppressive metabolites, which can impair T-cell function and promote regulatory T-cell (Treg) generation.
• IDO1 is largely viewed as a facilitator of tumor immune escape through its immunosuppressive actions, including the depletion of tryptophan and accumulation of kynurenine.

• Increased expression of IDO1 has been consistently linked to poorer outcomes across various cancer types.

• Although not oncogenic in itself, IDO1 enables a protumoral microenvironment by dampening anti-tumor immune responses.
Scientific Papers found: Click to Expand⟱
1044- Myr,    Myricetin inhibits interferon-γ-induced PD-L1 and IDO1 expression in lung cancer cells
- in-vitro, Lung, NA
PD-L1↓, IDO1↓,

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:


Core Metabolism/Glycolysis ⓘ

IDO1↓, 1,  

Immune & Inflammatory Signaling ⓘ

PD-L1↓, 1,  

Clinical Biomarkers ⓘ

PD-L1↓, 1,  
Total Targets: 3

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: IDO1, indoleamine 2, 3-dioxygenase 1
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#:127  Target#:975  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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