Myricetin / MAPK 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
MAPK, mitogen-activated protein kinase: Click to Expand ⟱
Source: CGL-CS
Type:
Mitogen-activated protein kinases (MAPKs) are a group of proteins involved in transmitting signals from the cell surface to the nucleus, playing a crucial role in various cellular processes, including growth, differentiation, and apoptosis (programmed cell death).

MAPK Pathways: The MAPK family includes several pathways, the most notable being:
1.ERK (Extracellular signal-Regulated Kinase): Often associated with cell proliferation and survival.
2.JNK (c-Jun N-terminal Kinase): Typically involved in stress responses and apoptosis.
3.p38 MAPK: Associated with inflammatory responses and apoptosis.

Inhibitors: Targeting the MAPK pathway has become a strategy in cancer therapy. For example, BRAF inhibitors (like vemurafenib) are used in treating melanoma with BRAF mutations.
Altered Expression Levels:
Overexpression: Many cancers exhibit overexpression of MAPK pathway components, such as RAS, BRAF, and MEK. This overexpression can lead to increased signaling activity, promoting cell proliferation and survival.
Downregulation: In some cases, negative regulators of the MAPK pathway (e.g., MAPK phosphatases) may be downregulated, leading to enhanced MAPK signaling.
The expression levels of MAPK pathway components can serve as biomarkers for cancer diagnosis, prognosis, and treatment response. For example, high levels of phosphorylated ERK (p-ERK) may indicate active MAPK signaling and poor prognosis in certain cancers.

Numerous reports indicate that the MAPK pathway plays a major role in tumor progression and invasion, while inhibition of MAPK signaling reduces invasion.
Scientific Papers found: Click to Expand⟱
1128- Myr,    Myricetin suppresses TGF-β-induced epithelial-to-mesenchymal transition in ovarian cancer
- vitro+vivo, Ovarian, NA
MAPK↓, ERK↓, PI3K↓, Akt↓, p‑PARP↑, cl‑Casp3↑, Bax:Bcl2↑, TumCMig↓, SMAD3↓,

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:


Cell Death ⓘ

Akt↓, 1,   Bax:Bcl2↑, 1,   cl‑Casp3↑, 1,   MAPK↓, 1,  

DNA Damage & Repair ⓘ

p‑PARP↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 1,   PI3K↓, 1,  

Migration ⓘ

SMAD3↓, 1,   TumCMig↓, 1,  
Total Targets: 9

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: MAPK, mitogen-activated protein kinase
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#:181  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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