Quercetin / ACTA2 Cancer Research Results

QC, Quercetin: Click to Expand ⟱

Features:

Plant pigment (flavonoid) found in red wine, onions, green tea, apples and berries.
Quercetin is thought to contribute to anticancer effects through several mechanisms:
-Antioxidant Activity:
-Induction of Apoptosis:modify Bax:Bcl-2 ratio
-Anti-inflammatory Effects:
-Cell Cycle Arrest:
-Inhibition of Angiogenesis and Metastasis: (VEGF)

Cellular Pathways:
-PI3K/Akt/mTOR Pathway: central to cell proliferation, survival, and metabolism.
-MAPK/ERK Pathway: influencing cell proliferation, differentiation, and apoptosis.
-NF-κB Pathway: downregulate NF-κB
-JAK/STAT Pathway: interfere with the activation of STAT3
-Apoptotic Pathways: intrinsic (mitochondrial) and extrinsic (death receptor-mediated) pathways

Quercetin has been used at doses around 500–1000 mg per day
Quercetin’s bioavailability from foods or standard supplements can be low.

-Note half-life 11 to 28 hours.
BioAv low 1-10%, poor water-solubility, consuming with fat may improve bioavialability. also piperine or VitC.
Pathways:
- induce ROS production in cancer cells (higher dose). Typicallys Lowers ROS in normal cells(unless it is high dose?)or depends on Redox status?. "quercetin paradox"
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓, Prx,
- Confusing info about Lowering AntiOxidant defense in Cancer Cells: NRF2↓(some contrary), TrxR↓**, SOD↓(contrary), GSH↓ Catalase↓(contrary), HO1↓(some contrary), GPx↓(some contrary)
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : NLRP3↓, IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, TIMP2, IGF-1↓, uPA↓, VEGF↓, ROCK1↓, FAK↓, NF-κB↓, CXCR4↓, SDF1↓, TGF-β↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMTs↓, EZH2↓, P53↑, HSP↓, Sp proteins↓, TET↑
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, FAK↓, ERK↓, EMT↓, TOP1↓, TET1,
- inhibits glycolysis and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, ECAR↓, OXPHOS↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, FGF↓, PDGF↓, EGFR↓,
- some indication of inhibiting Cancer Stem Cells : CSC↓, CK2↓, Hh↓, CD24↓, β-catenin↓, Notch2↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, α↓, ERK↓, JNK, - SREBP (related to cholesterol).
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

Rank	Pathway / Axis	Cancer Cells	Normal Cells	Label	Primary Interpretation	Notes
1	Reactive oxygen species (ROS)	↑ ROS (dose-, metal-, context-dependent)	↓ ROS	Conditional Driver	Biphasic redox modulation	Quercetin exhibits pro-oxidant behavior in cancer cells while protecting normal cells
2	Mitochondrial integrity / intrinsic apoptosis	↓ ΔΨm; ↑ caspase activation	↔ preserved	Driver	Execution of intrinsic apoptosis	Mitochondrial dysfunction is a central apoptosis route in cancer cells
3	PI3K → AKT → mTOR axis	↓ AKT / ↓ mTOR	↔ adaptive suppression	Driver	Growth and survival inhibition	AKT/mTOR suppression is a consistently reported upstream effect in cancer models
4	NF-κB signaling	↓ NF-κB activation	↓ inflammatory NF-κB tone	Secondary	Reduced survival and inflammatory transcription	NF-κB inhibition contributes to chemosensitization and apoptosis susceptibility
5	MAPK signaling (JNK / p38)	↑ JNK / ↑ p38	↔ minimal	Secondary	Stress-mediated apoptosis signaling	MAPK activation supports apoptosis downstream of redox stress
6	Cell cycle regulation	↑ G1/S or G2/M arrest	↔ largely spared	Phenotypic	Cytostatic growth control	Cell-cycle arrest reflects disruption of growth signaling
7	HIF-1α hypoxia signaling	↓ HIF-1α	↔ minimal	Secondary	Reduced hypoxia tolerance	Quercetin interferes with hypoxia-driven transcriptional programs
8	NRF2 antioxidant response	↑ NRF2 (adaptive, context-dependent)	↑ NRF2 (protective)	Adaptive	Stress compensation	NRF2 induction reflects redox buffering rather than primary cytotoxicity

ACTA2, Actin Alpha Cardiac Muscle 2: Click to Expand ⟱

Source:

Type:

ACTA2 (Actin Alpha Cardiac Muscle 2) is a gene that encodes a protein involved in the structure and function of smooth muscle cells. It plays a crucial role in various physiological processes, iACTA2 has been studied for its role in the tumor microenvironment, particularly in relation to cancer-associated fibroblasts (CAFs) and the extracellular matrix. CAFs, which often express ACTA2, can influence tumor progression, metastasis, and response to therapy. ncluding muscle contraction and the maintenance of vascular tone.
High levels of ACTA2 are often correlated with aggressive tumor behavior and poor patient outcomes.

Scientific Papers found: Click to Expand⟱

105-

RES,

QC,

The Effect of Resveratrol and Quercetin on Epithelial-Mesenchymal Transition in Pancreatic Cancer Stem Cell

in-vitro,

Pca,

PANC1

 10 uM

 CSCS (CD133-)

N-cadherin↓, TNF-α↓, ACTA2↓, EMT↓, CD133↓, CSCs↓,

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:

Proliferation, Differentiation & Cell State ⓘ

CD133↓, 1, CSCs↓, 1, EMT↓, 1,

Migration ⓘ

ACTA2↓, 1, N-cadherin↓, 1,

Immune & Inflammatory Signaling ⓘ

TNF-α↓, 1,
Total Targets: 6

Pathway results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: ACTA2, Actin Alpha Cardiac Muscle 2

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