Quercetin / Ca+2 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↑">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


Ca+2, Calcium Ion Ca+2: Click to Expand ⟱
Source:
Type:
In all eukaryotic cells, intracellular Ca2+ levels are maintained at low resting concentrations (approximately 100 nM) by the activity of the major Ca2+ extrusion system, the plasma membrane Ca2+-ATPase (PMCA), which exchanges extracellular protons (H+) for cytosolic Ca2+.
Indeed, sustained elevation of [Ca2+]C in the form of overload, saturating all Ca2+-dependent effectors, prolonged decrease in [Ca2+]ER, causing ER stress response, and high [Ca2+]M, inducing mitochondrial permeability transition (MPT), are considered to be pro-death factors.
In cancer the Ca2+-handling toolkit undergoes profound remodelling (figure 1) to favour activation of Ca2+-dependent transcription factors, such as the nuclear factor of activated T cells (NFAT), c-Myc, c-Jun, c-Fos that promote hypertrophic growth via induction of the expression of the G1 and G1/S phase transition cyclins (D and E) and associated cyclin-dependent kinases (CDK4 and CDK2).
Thus, cancer cells may evade apoptosis through decreasing calcium influx into the cytoplasm. This can be achieved by either downregulation of the expression of plasma membrane Ca2+-permeable ion channels or by reducing the effectiveness of the signalling pathways that activate these channels. Such protective measures would largely diminish the possibility of Ca2+ overload in response to pro-apoptotic stimuli, thereby impairing the effectiveness of mitochondrial and cytoplasmic apoptotic pathways.
Voltage-Gated Calcium Channels (VGCCs): Overexpression of VGCCs has been associated with increased tumor growth and metastasis in various cancers, including breast and prostate cancer.
Store-Operated Calcium Entry (SOCE): SOCE mechanisms, such as STIM1 and ORAI1, are often upregulated in cancer cells, contributing to enhanced cell survival and proliferation.
High intracellular calcium levels are associated with increased cell proliferation and migration, leading to a poorer prognosis. Calcium signaling can also influence hormone receptor status, affecting treatment responses.
Increased Ca²⁺ signaling is associated with advanced disease and metastasis. Patients with higher CaSR expression may have a worse prognosis due to enhanced tumor growth and resistance to apoptosis. -Ca2+ is an important regulator of the electric charge distribution of bio-membranes.
Scientific Papers found: Click to Expand⟱
923- QC,    Quercetin as an innovative therapeutic tool for cancer chemoprevention: Molecular mechanisms and implications in human health
- Review, Var, NA
ROS↑, GSH↓, Ca+2↝, MMP↓, Casp3↑, Casp8↑, Casp9↑, other↓, *ROS↓, *NRF2↑, HO-1↑, TumCCA↑, Inflam↓, STAT3↓, DR5↑, P450↓, MMPs↓, IFN-γ↓, IL6↓, COX2↓, IL8↓, iNOS↓, TNF-α↓, cl‑PARP↑, Apoptosis↑, P53↑, Sp1/3/4↓, survivin↓, TRAILR↑, Casp10↑, DFF45↑, TNFR 1↑, Fas↑, NF-kB↓, IKKα↓, cycD1/CCND1↓, Bcl-2↓, BAX↑, PI3K↓, Akt↓, E-cadherin↓, Vim↓, β-catenin/ZEB1↓, cMyc↓, EMT↓, MMP2↓, NOTCH1↓, MMP7↓, angioG↓, TSP-1↑, CSCs↓, XIAP↓, Snail↓, Slug↓, LEF1↓, P-gp↓, EGFR↓, GSK‐3β↓, mTOR↓, RAGE↓, HSP27↓, VEGF↓, TGF-β↓, COL1↓, COL3A1↓,
914- QC,    Quercetin and Cancer Chemoprevention
- Review, NA, NA
GSH↓, ROS↑, TumCCA↑, Ca+2↑, MMP↓, Casp3↑, Casp8↑, Casp9↑, β-catenin/ZEB1↓, AMPKα↑, ASK1↑, p38↑, TRAIL↑, DR5↑, cFLIP↓, Apoptosis↑,
91- QC,    The roles of endoplasmic reticulum stress and mitochondrial apoptotic signaling pathway in quercetin-mediated cell death of human prostate cancer PC-3 cells
- in-vitro, Pca, PC3
CDK2↓, cycE/CCNE↓, cycD1/CCND1↓, ATFs↑, GRP78/BiP↑, Bcl-2↓, BAX↑, Casp3↑, Casp8↑, Casp9↑, ER Stress↑, CHOP↑, TumCCA↑, DNAdam↑, AIF↑, Ca+2↑, MMP↓,
3353- QC,    Quercetin triggers cell apoptosis-associated ROS-mediated cell death and induces S and G2/M-phase cell cycle arrest in KON oral cancer cells
- in-vitro, Oral, KON - in-vitro, Nor, MRC-5
tumCV↓, selectivity↑, TumCCA↑, TumCMig↓, TumCI↓, Apoptosis↑, TumMeta↓, Bcl-2↓, BAX↑, TIMP1↑, MMP2↓, MMP9↓, *Inflam↓, *neuroP↑, *cardioP↑, p38↓, MAPK↓, Twist↓, P21↓, cycD1/CCND1↓, Casp3↑, Casp9↑, p‑Akt↓, p‑ERK↓, CD44↓, CD24↓, ChemoSen↑, MMP↓, Cyt‑c↑, AIF↑, ROS↑, Ca+2↑, Hif1a↓, VEGF↓,
3342- QC,    Quercetin modulates OTA-induced oxidative stress and redox signalling in HepG2 cells — up regulation of Nrf2 expression and down regulation of NF-κB and COX-2
- in-vitro, Nor, HepG2
*ROS↓, *Ca+2↓, *NF-kB↓, *NRF2↑, *COX2↓, *Inflam↓,
3341- QC,    Antioxidant Activities of Quercetin and Its Complexes for Medicinal Application
- Review, Var, NA - Review, Stroke, NA
*antiOx↑, *BioAv↑, *GSH↑, *AChE↓, *BChE↓, *H2O2↓, *lipid-P↓, *SOD↑, *SOD2↑, *Catalase↑, *GPx↑, *neuroP↑, *HO-1↑, *cardioP↑, *MDA↓, *NF-kB↓, *IKKα↓, *ROS↓, *PI3K↑, *Akt↑, *hepatoP↑, P53↑, BAX↑, IGF-1R↓, Akt↓, AR↓, TumCP↓, GSH↑, SOD↑, Catalase↑, lipid-P↓, *TNF-α↓, *Ca+2↓,
3374- QC,    Therapeutic effects of quercetin in oral cancer therapy: a systematic review of preclinical evidence focused on oxidative damage, apoptosis and anti-metastasis
- Review, Oral, NA - Review, AD, NA
α-SMA↓, α-SMA↑, TumCP↓, tumCV↓, TumVol↓, TumCI↓, TumMeta↓, TumCMig↓, ROS↑, Apoptosis↑, BioAv↓, *neuroP↑, *antiOx↑, *Inflam↓, *Aβ↓, *cardioP↑, MMP↓, Cyt‑c↑, MMP2↓, MMP9↓, EMT↓, MMPs↓, Twist↓, Slug↓, Ca+2↑, AIF↑, Endon↑, P-gp↓, LDH↑, HK2↓, PKA↓, Glycolysis↓, GlucoseCon↓, lactateProd↓, GRP78/BiP↑, Casp12↑, CHOP↑,
3372- QC,  FIS,  KaempF,    Anticancer Potential of Selected Flavonols: Fisetin, Kaempferol, and Quercetin on Head and Neck Cancers
- Review, HNSCC, NA
ROCK1↑, TumCCA↓, HSPs↓, RAS↓, ROS↑, Ca+2↑, MMP↓, Cyt‑c↑, Endon↑, MMP9↓, MMP2↓, MMP7↓, MMP-10↓, VEGF↓, NF-kB↓, p65↓, iNOS↓, COX2↓, uPA↓, PI3K↓, FAK↓, MEK↓, ERK↓, JNK↓, p38↓, cJun↓, FOXO3↑,

Showing Research Papers: 1 to 8 of 8

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 8

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Catalase↑, 1,   GSH↓, 2,   GSH↑, 1,   HO-1↑, 1,   lipid-P↓, 1,   ROS↑, 5,   SOD↑, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 3,   MEK↓, 1,   MMP↓, 6,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 1,   GlucoseCon↓, 1,   Glycolysis↓, 1,   HK2↓, 1,   lactateProd↓, 1,   LDH↑, 1,  

Cell Death ⓘ

Akt↓, 2,   p‑Akt↓, 1,   Apoptosis↑, 4,   ASK1↑, 1,   BAX↑, 4,   Bcl-2↓, 3,   Casp10↑, 1,   Casp12↑, 1,   Casp3↑, 4,   Casp8↑, 3,   Casp9↑, 4,   cFLIP↓, 1,   Cyt‑c↑, 3,   DR5↑, 2,   Endon↑, 2,   Fas↑, 1,   iNOS↓, 2,   JNK↓, 1,   MAPK↓, 1,   p38↓, 2,   p38↑, 1,   survivin↓, 1,   TNFR 1↑, 1,   TRAIL↑, 1,   TRAILR↑, 1,  

Kinase & Signal Transduction ⓘ

AMPKα↑, 1,   Sp1/3/4↓, 1,  

Transcription & Epigenetics ⓘ

cJun↓, 1,   other↓, 1,   tumCV↓, 2,  

Protein Folding & ER Stress ⓘ

ATFs↑, 1,   CHOP↑, 2,   ER Stress↑, 1,   GRP78/BiP↑, 2,   HSP27↓, 1,   HSPs↓, 1,  

DNA Damage & Repair ⓘ

DFF45↑, 1,   DNAdam↑, 1,   P53↑, 2,   cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 1,   cycD1/CCND1↓, 3,   cycE/CCNE↓, 1,   P21↓, 1,   TumCCA↓, 1,   TumCCA↑, 4,  

Proliferation, Differentiation & Cell State ⓘ

CD24↓, 1,   CD44↓, 1,   CSCs↓, 1,   EMT↓, 2,   ERK↓, 1,   p‑ERK↓, 1,   FOXO3↑, 1,   GSK‐3β↓, 1,   IGF-1R↓, 1,   mTOR↓, 1,   NOTCH1↓, 1,   PI3K↓, 2,   RAS↓, 1,   STAT3↓, 1,  

Migration ⓘ

Ca+2↑, 5,   Ca+2↝, 1,   COL1↓, 1,   COL3A1↓, 1,   E-cadherin↓, 1,   FAK↓, 1,   LEF1↓, 1,   MMP-10↓, 1,   MMP2↓, 4,   MMP7↓, 2,   MMP9↓, 3,   MMPs↓, 2,   PKA↓, 1,   RAGE↓, 1,   ROCK1↑, 1,   Slug↓, 2,   Snail↓, 1,   TGF-β↓, 1,   TIMP1↑, 1,   TSP-1↑, 1,   TumCI↓, 2,   TumCMig↓, 2,   TumCP↓, 2,   TumMeta↓, 2,   Twist↓, 2,   uPA↓, 1,   Vim↓, 1,   α-SMA↓, 1,   α-SMA↑, 1,   β-catenin/ZEB1↓, 2,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   EGFR↓, 1,   Hif1a↓, 1,   VEGF↓, 3,  

Barriers & Transport ⓘ

P-gp↓, 2,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   IFN-γ↓, 1,   IKKα↓, 1,   IL6↓, 1,   IL8↓, 1,   Inflam↓, 1,   NF-kB↓, 2,   p65↓, 1,   TNF-α↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   ChemoSen↑, 1,   P450↓, 1,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

AR↓, 1,   EGFR↓, 1,   IL6↓, 1,   LDH↑, 1,   RAGE↓, 1,  

Functional Outcomes ⓘ

TumVol↓, 1,  
Total Targets: 132

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   Catalase↑, 1,   GPx↑, 1,   GSH↑, 1,   H2O2↓, 1,   HO-1↑, 1,   lipid-P↓, 1,   MDA↓, 1,   NRF2↑, 2,   ROS↓, 3,   SOD↑, 1,   SOD2↑, 1,  

Cell Death ⓘ

Akt↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

PI3K↑, 1,  

Migration ⓘ

Ca+2↓, 2,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IKKα↓, 1,   Inflam↓, 3,   NF-kB↓, 2,   TNF-α↓, 1,  

Synaptic & Neurotransmission ⓘ

AChE↓, 1,   BChE↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 1,  

Functional Outcomes ⓘ

cardioP↑, 3,   hepatoP↑, 1,   neuroP↑, 3,  
Total Targets: 27

Scientific Paper Hit Count for: Ca+2, Calcium Ion Ca+2
8 Quercetin
1 Fisetin
1 Kaempferol
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#:140  Target#:38  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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