Quercetin / ROS 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↓">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


ROS, Reactive Oxygen Species: Click to Expand ⟱
Source: HalifaxProj (inhibit)
Type:
Reactive oxygen species (ROS) are highly reactive molecules that contain oxygen and can lead to oxidative stress in cells. They play a dual role in cancer biology, acting as both promoters and suppressors of cancer.
ROS can cause oxidative damage to DNA, leading to mutations that may contribute to cancer initiation and progression. So normally you want to inhibit ROS to prevent cell mutations.
However excessive ROS can induce apoptosis (programmed cell death) in cancer cells, potentially limiting tumor growth. Chemotherapy typically raises ROS.
-mitochondria is the main source of reactive oxygen species (ROS) (and the ETC is heavily related)

"Reactive oxygen species (ROS) are two electron reduction products of oxygen, including superoxide anion, hydrogen peroxide, hydroxyl radical, lipid peroxides, protein peroxides and peroxides formed in nucleic acids 1. They are maintained in a dynamic balance by a series of reduction-oxidation (redox) reactions in biological systems and act as signaling molecules to drive cellular regulatory pathways."
"During different stages of cancer formation, abnormal ROS levels play paradoxical roles in cell growth and death 8. A physiological concentration of ROS that maintained in equilibrium is necessary for normal cell survival. Ectopic ROS accumulation promotes cell proliferation and consequently induces malignant transformation of normal cells by initiating pathological conversion of physiological signaling networks. Excessive ROS levels lead to cell death by damaging cellular components, including proteins, lipid bilayers, and chromosomes. Therefore, both scavenging abnormally elevated ROS to prevent early neoplasia and facilitating ROS production to specifically kill cancer cells are promising anticancer therapeutic strategies, in spite of their contradictoriness and complexity."
"ROS are the collection of derivatives of molecular oxygen that occur in biology, which can be categorized into two types, free radicals and non-radical species. The non-radical species are hydrogen peroxide (H 2O 2 ), organic hydroperoxides (ROOH), singlet molecular oxygen ( 1 O 2 ), electronically excited carbonyl, ozone (O3 ), hypochlorous acid (HOCl, and hypobromous acid HOBr). Free radical species are super-oxide anion radical (O 2•−), hydroxyl radical (•OH), peroxyl radical (ROO•) and alkoxyl radical (RO•) [130]. Any imbalance of ROS can lead to adverse effects. H2 O 2 and O 2 •− are the main redox signalling agents. The cellular concentration of H2 O 2 is about 10−8 M, which is almost a thousand times more than that of O2 •−".
"Radicals are molecules with an odd number of electrons in the outer shell [393,394]. A pair of radicals can be formed by breaking a chemical bond or electron transfer between two molecules."

Recent investigations have documented that polyphenols with good antioxidant activity may exhibit pro-oxidant activity in the presence of copper ions, which can induce apoptosis in various cancer cell lines but not in normal cells. "We have shown that such cell growth inhibition by polyphenols in cancer cells is reversed by copper-specific sequestering agent neocuproine to a significant extent whereas iron and zinc chelators are relatively ineffective, thus confirming the role of endogenous copper in the cytotoxic action of polyphenols against cancer cells. Therefore, this mechanism of mobilization of endogenous copper." > Ions could be one of the important mechanisms for the cytotoxic action of plant polyphenols against cancer cells and is possibly a common mechanism for all plant polyphenols. In fact, similar results obtained with four different polyphenolic compounds in this study, namely apigenin, luteolin, EGCG, and resveratrol, strengthen this idea.
Interestingly, the normal breast epithelial MCF10A cells have earlier been shown to possess no detectable copper as opposed to breast cancer cells [24], which may explain their resistance to polyphenols apigenin- and luteolin-induced growth inhibition as observed here (Fig. 1). We have earlier proposed [25] that this preferential cytotoxicity of plant polyphenols toward cancer cells is explained by the observation made several years earlier, which showed that copper levels in cancer cells are significantly elevated in various malignancies. Thus, because of higher intracellular copper levels in cancer cells, it may be predicted that the cytotoxic concentrations of polyphenols required would be lower in these cells as compared to normal cells."

Majority of ROS are produced as a by-product of oxidative phosphorylation, high levels of ROS are detected in almost all cancers.
-It is well established that during ER stress, cytosolic calcium released from the ER is taken up by the mitochondrion to stimulate ROS overgeneration and the release of cytochrome c, both of which lead to apoptosis.

Note: Products that may raise ROS can be found using this database, by:
Filtering on the target of ROS, and selecting the Effect Direction of ↑

Targets to raise ROS (to kill cancer cells):
• NADPH oxidases (NOX): NOX enzymes are involved in the production of ROS.
    -Targeting NOX enzymes can increase ROS levels and induce cancer cell death.
    -eNOX2 inhibition leads to a high NADH/NAD⁺ ratio which can lead to increased ROS
• Mitochondrial complex I: Inhibiting can increase ROS production
• P53: Activating p53 can increase ROS levels(by inducing the expression of pro-oxidant genes)
• Nrf2 inhibition: regulates the expression of antioxidant genes. Inhibiting Nrf2 can increase ROS levels
• Glutathione (GSH): an antioxidant. Depleting GSH can increase ROS levels
• Catalase: Catalase converts H2O2 into H2O+O. Inhibiting catalase can increase ROS levels
• SOD1: converts superoxide into hydrogen peroxide. Inhibiting SOD1 can increase ROS levels
• PI3K/AKT pathway: regulates cell survival and metabolism. Inhibiting can increase ROS levels
• HIF-1α inhibition: regulates genes involved in metabolism and angiogenesis. Inhibiting HIF-1α can increase ROS
• Glycolysis: Inhibiting glycolysis can increase ROS levels • Fatty acid oxidation: Cancer cells often rely on fatty acid oxidation for energy production.
-Inhibiting fatty acid oxidation can increase ROS levels
• ER stress: Endoplasmic reticulum (ER) stress can increase ROS levels
• Autophagy: process by which cells recycle damaged organelles and proteins.
-Inhibiting autophagy can increase ROS levels and induce cancer cell death.
• KEAP1/Nrf2 pathway: regulates the expression of antioxidant genes.
    -Inhibiting KEAP1 or activating Nrf2 can increase ROS levels and induce cancer cell death.
• DJ-1: regulates the expression of antioxidant genes. Inhibiting DJ-1 can increase ROS levels
• PARK2: regulates the expression of antioxidant genes. Inhibiting PARK2 can increase ROS levels
• SIRT1 inhibition:regulates the expression of antioxidant genes. Inhibiting SIRT1 can increase ROS levels
• AMPK activation: regulates energy metabolism and can increase ROS levels when activated.
• mTOR inhibition: regulates cell growth and metabolism. Inhibiting mTOR can increase ROS levels
• HSP90 inhibition: regulates protein folding and can increase ROS levels when inhibited.
• Proteasome: degrades damaged proteins. Inhibiting the proteasome can increase ROS levels
• Lipid peroxidation: a process by which lipids are oxidized, leading to the production of ROS.
    -Increasing lipid peroxidation can increase ROS levels
• Ferroptosis: form of cell death that is regulated by iron and lipid peroxidation.
    -Increasing ferroptosis can increase ROS levels
• Mitochondrial permeability transition pore (mPTP): regulates mitochondrial permeability.
    -Opening the mPTP can increase ROS levels
• BCL-2 family proteins: regulate apoptosis and can increase ROS levels when inhibited.
• Caspase-independent cell death: a form of cell death that is regulated by ROS.
    -Increasing caspase-independent cell death can increase ROS levels
• DNA damage response: regulates the repair of DNA damage. Increasing DNA damage can increase ROS
• Epigenetic regulation: process by which gene expression is regulated.
    -Increasing epigenetic regulation can increase ROS levels

-PKM2, but not PKM1, can be inhibited by direct oxidation of cysteine 358 as an adaptive response to increased intracellular reactive oxygen species (ROS)

ProOxidant Strategy:(inhibit the Mevalonate Pathway (likely will also inhibit GPx)
-HydroxyCitrate (HCA) found as supplement online and typically used in a dose of about 1.5g/day or more
-Atorvastatin typically 40-80mg/day, -Dipyridamole typically 200mg 2x/day Combined effect research
-Lycopene typically 100mg/day range (note debatable as it mainly lowers NRF2)

Dual Role of Reactive Oxygen Species and their Application in Cancer Therapy 
ROS-Inducing Interventions in Cancer — Canonical + Mechanistic Reference
-generated from AI and Cancer database
ROS rating:  +++ strong | ++ moderate | + weak | ± mixed | 0 none
NRF2:        ↓ suppressed | ↑ activated | ± mixed | 0 none
Conditions:  [D] dose  [Fe] metal  [M] metabolic  [O₂] oxygen
             [L] light [F] formulation [T] tumor-type [C] combination




Item ROS↑ NRF2 Condition Mechanism Class Remarks 



ROS">Piperlongumine
+++ ↓ [D][T] ROS-dominant






ROS">Shikonin
+++↓/±[D][T]ROS-dominant






ROS">Vitamin K3 (menadione)
+++↓[D]ROS-dominant






ROS">Copper (ionic / nano)
+++↓[Fe][F]ROS-dominant






ROS">Sodium Selenite
+++↓[D]ROS-dominant






ROS">Juglone
+++↓[D]ROS-dominant






ROS">Auranofin
+++↓[D]ROS-dominant






ROS">Photodynamic Therapy (PDT)
+++0[L][O₂]ROS-dominant






ROS">Radiotherapy / Radiation
+++0[O₂]ROS-dominant






ROS">Doxorubicin
+++↓[D]ROS-dominant






ROS">Cisplatin
++↓[D][T]ROS-dominant






ROS">Salinomycin
++↓[D][T]ROS-dominant






ROS">Artemisinin / DHA
++↓[Fe][T]ROS-dominant






ROS">Sulfasalazine
++↓[C][T]ROS-dominant






ROS">FMD / fasting
++↓[M][C][O₂]ROS-dominant






ROS">Vitamin C (pharmacologic)
++↓[Fe][D]ROS-dominant






ROS">Silver nanoparticles
++±[F][D]ROS-dominant






ROS">Gambogic acid
++↓[D][T]ROS-dominant






ROS">Parthenolide
++↓[D][T]ROS-dominant






ROS">Plumbagin
++↓[D]ROS-dominant






ROS">Allicin
++↓[D]ROS-dominant






ROS">Ashwagandha (Withaferin A)
++↓[D][T]ROS-dominant






ROS">Berberine
++↓[D][M]ROS-dominant






ROS">PEITC
++↓[D][C]ROS-dominant






ROS">Methionine restriction
+↓[M][C][T]ROS-secondary






ROS">DCA
+±[M][T]ROS-secondary






ROS">Capsaicin
+±[D][T]ROS-secondary






ROS">Galloflavin
+0[D]ROS-secondary






ROS">Piperine
+±[D][F]ROS-secondary






ROS">Propyl gallate
+↓[D]ROS-secondary






ROS">Scoulerine
+?[D][T]ROS-secondary






ROS">Thymoquinone
±±[D][T]Dual redox






ROS">Emodin
±±[D][T]Dual redox






ROS">Alpha-lipoic acid (ALA)
±↑[D][M]NRF2-dominant






ROS">Curcumin
±↑/↓[D][F]NRF2-dominant






ROS">EGCG
±↑/↓[D][O₂]NRF2-dominant






ROS">Quercetin
±↑/↓[D][Fe]NRF2-dominant






ROS">Resveratrol
±↑[D][M]NRF2-dominant






ROS">Sulforaphane
±↑↑[D]NRF2-dominant






ROS">Lycopene
0↑—Antioxidant






ROS">Rosmarinic acid
0↑—Antioxidant






ROS">Citrate
00—Neutral


Scientific Papers found: Click to Expand⟱
6027- CGA,  CUR,  EGCG,  QC,  RES  Contribution of Non-Coding RNAs to Anticancer Effects of Dietary Polyphenols: Chlorogenic Acid, Curcumin, Epigallocatechin-3-Gallate, Genistein, Quercetin and Resveratrol
- Review, Nor, NA
*ROS↓, ROS↑,
912- QC,  2DG,    Selected polyphenols potentiate the apoptotic efficacy of glycolytic inhibitors in human acute myeloid leukemia cell lines. Regulation by protein kinase activities
Apoptosis↑, ROS↓, GSH∅, other↑,
894- QC,    The antioxidant, rather than prooxidant, activities of quercetin on normal cells: quercetin protects mouse thymocytes from glucose oxidase-mediated apoptosis
- in-vitro, Nor, NA
Apoptosis↑, *NF-kB↓, *AP-1↓, *P53↝, *ROS↓,
3338- QC,    Quercetin: Its Antioxidant Mechanism, Antibacterial Properties and Potential Application in Prevention and Control of Toxipathy
- Review, Var, NA - Review, Stroke, NA
*antiOx↑, *GSH↑, *ROS↓, *Dose↑, *NADPH↓, *AMP↓, *NF-kB↓, *p38↑, *MAPK↑, *SOD↑, *MDA↓, *iNOS↓, *Catalase↑, *PI3K↑, *Akt↑, *lipid-P↓, *memory↑, *radioP↑, *neuroP↑, *MDA↓,
3336- QC,    Neuroprotective Effects of Quercetin in Alzheimer’s Disease
- Review, AD, NA
*neuroP↑, *lipid-P↓, *antiOx↑, *Aβ↓, *Inflam↓, *BBB↝, *NF-kB↓, *iNOS↓, *memory↑, *cognitive↑, *AChE↓, *MMP↑, *ROS↓, *ATP↑, *AMPK↑, *NADPH↓, *p‑tau↓,
2431- QC,    The Protective Effect of Quercetin against the Cytotoxicity Induced by Fumonisin B1 in Sertoli Cells
- in-vitro, Nor, TM4
*Apoptosis↓, *ROS↓, *antiOx↓, *MMP↑, *GPI↑, *HK2↑, *ALDOA↑, *PKM1↑, *LDHA↑, *PFKL↑,
2343- QC,    Pharmacological Activity of Quercetin: An Updated Review
- Review, Nor, NA
*ROS↓, *GSH↑, *Catalase↑, *SOD↑, *MDA↓, *GPx↑, *Copper↓, *Iron↓, Apoptosis↓, TumCCA↑, MMP2↓, MMP9↓, GlucoseCon↓, lactateProd↓, PKM2↓, GLUT1↓, LDHA↓, ROS↑,
2338- QC,    Quercetin: A Flavonoid with Potential for Treating Acute Lung Injury
- Review, Nor, NA
*SIRT1↑, *NLRP3↓, *Inflam↓, *TNF-α↓, *IL1β↓, *IL6↓, *PKM2↓, *HO-1↑, *ROS↓, *NO↓, *MDA↓, *antiOx↑, *COX2↓, *HMGB1↓, *iNOS↓, *NF-kB↓,
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↓,
68- QC,  BaP,    Differential protein expression of peroxiredoxin I and II by benzo(a)pyrene and quercetin treatment in 22Rv1 and PrEC prostate cell lines
- in-vitro, Pca, 22Rv1 - in-vitro, Pca, PrEC
PrxI∅, PrxII∅, *toxicity↓, ROS↓, ROS↑, ROS∅, chemoP↑, PrxII↑, i-H2O2↓,
3607- QC,    Mechanisms of Neuroprotection by Quercetin: Counteracting Oxidative Stress and More
- Review, AD, NA - Review, Park, NA
*neuroP↑, *NRF2↑, *PONs↑, *antiOx↑, *Inflam↓, *SIRT1↑, *eff↑, *ROS↓, *cognitive↑, *eff↑, *lipid-P↓, *GSH↑, *GPx↑, *SOD↑, *NRF2↑,
3605- QC,    Protective effect of quercetin in primary neurons against Aβ(1–42): relevance to Alzheimer's disease
- Review, AD, NA
*Aβ↓, *ROS↓, *lipid-P↓, *Apoptosis↓,
3340- QC,    Quercetin regulates inflammation, oxidative stress, apoptosis, and mitochondrial structure and function in H9C2 cells by promoting PVT1 expression
- in-vitro, Nor, H9c2
*Inflam↓, *ROS↓, *Apoptosis↓,
3603- QC,    Mechanism of quercetin therapeutic targets for Alzheimer disease and type 2 diabetes mellitus
- Review, AD, NA - Review, Diabetic, NA
*MAPK↓, *neuroP↑, *ROS↓, *Akt↓, *PI3K↓, *IL6↓, *TNF-α↓, *VEGF↓, *EGFR↓, *Casp3↓, *Bcl-2↓, *IL1β↓,
3602- QC,    The flavonoid quercetin ameliorates Alzheimer's disease pathology and protects cognitive and emotional function in aged triple transgenic Alzheimer's disease model mice
- in-vivo, AD, NA
*BACE↓, *cognitive↑, *ROS↓, *lipid-P↓, *iNOS↓, *COX2↓, *BBB↑, *neuroP↑, *other↓, *memory↑,
3601- QC,    Overviews of Biological Importance of Quercetin: A Bioactive Flavonoid
- Review, Var, NA - Review, AD, NA
*Inflam↓, *cardioP↑, AntiCan↑, AntiTum↑, *neuroP↑, *cognitive↑, *ROS↓, *BP↓, *LDL↓,
3534- QC,  Lyco,    Synergistic protection of quercetin and lycopene against oxidative stress via SIRT1-Nox4-ROS axis in HUVEC cells
- in-vitro, Nor, HUVECs
*ROS↓, *NOX4↓, *Inflam↓, *NF-kB↓, *p65↓, *SIRT1↑, *cardioP↑, *IL6↓, *COX2↓,
4296- QC,    A Flavonoid on the Brain: Quercetin as a Potential Therapeutic Agent in Central Nervous System Disorders
- Review, AD, NA
*Inflam↓, *COX2↓, *5LO↓, *antiOx↑, *BioAv↝, *GPx↑, *SOD↑, *Ach↑, *4-HNE↓, *CREB↑, *BDNF↑, *ROS↓, *GSH↑, *IL1β↓, *IL6↓, *TNF-α↓,
4787- QC,    Quercetin: A Phytochemical with Pro-Apoptotic Effects in Colon Cancer Cells
- Review, CRC, NA
Inflam↓, AntiCan↑, Apoptosis↑, MMP↓, P53↑, BAX↑, Casp3↑, Casp9↑, Bcl-2↓, NF-kB↓, IL6↓, IL1β↓, *antiOx↑, *lipid-P↓, *ROS↓, MAPK↓, JAK↓, STAT↓, PI3K↓, Akt↓, chemoP↑, ROS⇅, DNAdam↑, ChemoSen↝,
4827- QC,  CUR,    Synthetic Pathways and the Therapeutic Potential of Quercetin and Curcumin
- Review, Var, NA
*AntiCan↑, *Inflam↓, *Bacteria↓, *AntiDiabetic↑, *ROS↓, *SOD↑, *Catalase↑, *GSH↑, *NRF2↑, *Trx↑, *IronCh↑, *MDA↑, cycD1/CCND1↓, PI3K↓, Casp3↑, BAX↑, ChemoSen↑, ROS↑, eff↑, MMP↓, Cyt‑c↑, Akt↓, ERK↓,
5025- QC,    New perspectives on the therapeutic potential of quercetin in non-communicable diseases: Targeting Nrf2 to counteract oxidative stress and inflammation
- Review, Nor, NA
*antiOx↑, *Inflam↓, *NRF2↓, *ROS↓, *cardioP↑, *HO-1↑, *Catalase↑, *GPx↑, *NQO1↑, *SIRT1↑,
5028- QC,    Quercetin inhibited LPS-induced cytokine storm by interacting with the AKT1-FoxO1 and Keap1-Nrf2 signaling pathway in macrophages
- vitro+vivo, Nor, RAW264.7
*ROS↓, *Keap1↓, *NRF2↑,
3349- QC,    ROS_and_Downregulation_of_High_Mobility_Group_Box_1_HMGB1_Protein_Expression">Quercetin Exerted Protective Effects in a Rat Model of Sepsis via Inhibition of Reactive Oxygen Species (ROS) and Downregulation of High Mobility Group Box 1 (HMGB1) Protein Expression
- in-vivo, Sepsis, NA
*Sepsis↓, *ROS↓, *SOD↑, *Catalase↑, *HMGB1↓, *Inflam↓, *TAC↑,
3354- QC,    Quercetin: Its Main Pharmacological Activity and Potential Application in Clinical Medicine
- Review, Var, NA
*ROS↓, *IronCh↓, *lipid-P↓, *GSH↑, *NRF2↑, TumCCA↑, ER Stress↑, P53↑, CDK2↓, cycA1/CCNA1↓, CycB/CCNB1↓, cycE/CCNE↓, cycD1/CCND1↓, PCNA↓, P21↑, p27↑, PI3K↓, Akt↓, mTOR↓, STAT3↓, cFLIP↓, cMyc↓, survivin↓, DR5↓, *Inflam↓, *IL6↓, *IL8↓, COX2↓, 5LO↓, *cardioP↑, *FASN↓, *AntiAg↑, *MDA↓,
3351- QC,    Quercetin Exerts Differential Neuroprotective Effects Against H2O2 and Aβ Aggregates in Hippocampal Neurons: the Role of Mitochondria
- Review, AD, NA
*ROS↓, *neuroP↑,
3376- QC,    Inhibiting CDK6 Activity by Quercetin Is an Attractive Strategy for Cancer Therapy
- in-vitro, BC, MCF-7 - in-vitro, Lung, A549
CDK6↓, tumCV↓, Apoptosis↑, ROS↓, eff↑,
3348- QC,    Quercetin and iron metabolism: What we know and what we need to know
- Review, NA, NA
*IronCh↑, *ROS↓, *AntiAg↑, *Fenton↓, *lipid-P↓, *hepatoP↑, *RenoP↑, HIF-1↑, ROS↑,
3347- QC,    Recent Advances in Potential Health Benefits of Quercetin
- Review, Var, NA - Review, AD, NA
*antiOx↑, *ROS↓, *Inflam↓, TumCP↓, Apoptosis↑, *cardioP↑, *BP↓, TumMeta↓, MDR1↓, NADPH↓, ChemoSen↑, MMPs↓, TIMP2↑, *NLRP3↓, *IFN-γ↑, *COX2↓, *NF-kB↓, *MAPK↓, *CRP↓, *IL6↓, *TNF-α↓, *IL1β↓, *TLR4↑, *PKCδ↓, *AP-1↓, *ICAM-1↓, *NRF2↑, *HO-1↑, *lipid-P↓, *neuroP↑, *eff↑, *memory↑, *cognitive↑, *AChE↓, *BioAv↑, *BioAv↑, *BioAv↑, *BioAv↑, *BioAv↑,
3346- QC,    ROS_Level_Is_Critical_for_the_Antiproliferative_Effect_of_Quercetin_in_the_Hepatocellular_Carcinoma_Cell_Line_HepG2">Regulation of the Intracellular ROS Level Is Critical for the Antiproliferative Effect of Quercetin in the Hepatocellular Carcinoma Cell Line HepG2
- in-vitro, Liver, HepG2 - in-vitro, Liver, HUH7
TumCCA↑, Apoptosis↑, P53↑, TumCP↓, ROS↓, antiOx↑, HO-1↑, CDK1↓,
3343- QC,    Quercetin, a Flavonoid with Great Pharmacological Capacity
- Review, Var, NA - Review, AD, NA - Review, Arthritis, NA
*antiOx↑, *ROS↓, *angioG↓, *Inflam↓, *BioAv↓, *Half-Life↑, *GSH↑, *SOD↑, *Catalase↑, *Nrf1↑, *BP↓, *cardioP↑, *IL10↓, *TNF-α↓, *Aβ↓, *GSK‐3β↓, *tau↓, *neuroP↑, *Pain↓, *COX2↓, *NRF2↑, *HO-1↑, *IL1β↓, *IL17↓, *MCP1↓, PKCδ↓, ERK↓, BAX↓, cMyc↓, KRAS↓, ROS↓, selectivity↑, tumCV↓, Apoptosis↑, TumCCA↑, eff↑, P-gp↓, eff↑, eff↑, eff↑, eff↑, CycB/CCNB1↓, CDK1↓, CDK4↓, CDK2↓, TOP2↓, Cyt‑c↑, cl‑PARP↑, MMP↓, HSP70/HSPA5↓, HSP90↓, MDM2↓, RAS↓, eff↑,
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↓,
3339- QC,    Quercetin suppresses ROS production and migration by specifically targeting Rac1 activation in gliomas
- in-vitro, GBM, C6 - in-vitro, GBM, IMR32
BBB↑, tumCV↓, TumCMig↓, Rac1↓, p66Shc↓, ROS↓,
3369- QC,    Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects
- Review, Pca, NA
FAK↓, TumCCA↑, p‑pRB↓, CDK2↑, CycB/CCNB1↓, CDK1↓, EMT↓, PI3K↓, MAPK↓, Wnt↓, ROS↑, miR-21↑, Akt↓, NF-kB↓, FasL↑, Bak↑, BAX↑, Bcl-2↓, Casp3↓, Casp9↑, P53↑, p38↑, MAPK↑, Cyt‑c↑, PARP↓, CHOP↑, ROS↓, LDH↑, GRP78/BiP↑, ERK↑, MDA↓, SOD↑, GSH↑, NRF2↑, VEGF↓, PDGF↓, EGF↓, FGF↓, TNF-α↓, TGF-β↓, VEGFR2↓, EGFR↓, FGFR1↓, mTOR↓, cMyc↓, MMPs↓, LC3B-II↑, Beclin-1↑, IL1β↓, CRP↓, IL10↓, COX2↓, IL6↓, TLR4↓, Shh↓, HER2/EBBR2↓, NOTCH↓, DR5↑, HSP70/HSPA5↓, CSCs↓, angioG↓, MMP2↓, MMP9↓, IGFBP3↑, uPA↓, uPAR↓, RAS↓, Raf↓, TSP-1↑,
3368- QC,    The potential anti-cancer effects of quercetin on blood, prostate and lung cancers: An update
- Review, Var, NA
*Inflam↓, *antiOx↑, *AntiCan↑, Casp3↓, p‑Akt↓, p‑mTOR↓, p‑ERK↓, β-catenin/ZEB1↓, Hif1a↓, AntiAg↓, VEGFR2↓, EMT↓, EGFR↓, MMP2↓, MMP↓, TumMeta↓, MMPs↓, Akt↓, Snail↓, N-cadherin↓, Vim↓, E-cadherin↑, STAT3↓, TGF-β↓, ROS↓, P53↑, BAX↑, PKCδ↓, PI3K↓, COX2↓, cFLIP↓, cycD1/CCND1↓, cMyc↓, IL6↓, IL10↓, Cyt‑c↑, TumCCA↑, DNMTs↓, HDAC↓, ac‑H3↑, ac‑H4↑, Diablo↑, Casp3↑, Casp9↑, PARP1↑, eff↑, PTEN↑, VEGF↓, NO↓, iNOS↓, ChemoSen↑, eff↑, eff↑, eff↑, uPA↓, CXCR4↓, CXCL12↓, CLDN2↓, CDK6↓, MMP9↓, TSP-1↑, Ki-67↓, PCNA↓, ROS↑, ER Stress↑,
3366- QC,    Quercetin Attenuates Endoplasmic Reticulum Stress and Apoptosis in TNBS-Induced Colitis by Inhibiting the Glucose Regulatory Protein 78 Activation
- in-vivo, IBD, NA
*Apoptosis↓, *Inflam↓, *ROS↓, *ER Stress↓, *TNF-α↓, *MPO↓, *p‑JNK↓, *Casp12↓, *GRP78/BiP↓, *antiOx↑, *NF-kB↓,
3365- QC,    Quercetin attenuates sepsis-induced acute lung injury via suppressing oxidative stress-mediated ER stress through activation of SIRT1/AMPK pathways
- in-vivo, Sepsis, NA
*ER Stress↓, *PDI↓, *CHOP↓, *GRP78/BiP↓, *ATF6↓, *PERK↓, *IRE1↓, *MMP↑, *SOD↑, *ROS↓, *MDA↓, *SIRT1↑, *AMPK↑, *Sepsis↓,
3363- QC,    The Protective Effect of Quercetin on Endothelial Cells Injured by Hypoxia and Reoxygenation
- in-vitro, Nor, HBMECs
*Apoptosis↓, *angioG↑, *NRF2↑, *Keap1↓, *ATF6↓, *GRP78/BiP↓, *CLDN5↑, *ZO-1↑, *MMP↑, *BBB↑, *ROS↓, *ER Stress↓,
3361- QC,    Quercetin ameliorates testosterone secretion disorder by inhibiting endoplasmic reticulum stress through the miR-1306-5p/HSD17B7 axis in diabetic rats
- in-vivo, Nor, NA - in-vitro, NA, NA
*BG↓, *ROS↓, *SOD↑, *MDA↓, *ER Stress↓, *iNOS↓, *CHOP↓, *GRP78/BiP↓, *antiOx↓, *Inflam↓, *JAK2↑, *STAT3?,

Showing Research Papers: 1 to 39 of 39

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 39

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   Catalase↑, 1,   GSH↓, 1,   GSH↑, 2,   GSH∅, 1,   i-H2O2↓, 1,   HO-1↑, 2,   lipid-P↓, 1,   MDA↓, 1,   NRF2↑, 1,   p66Shc↓, 1,   PrxI∅, 1,   PrxII↑, 1,   PrxII∅, 1,   ROS↓, 8,   ROS↑, 8,   ROS⇅, 1,   ROS∅, 1,   SOD↑, 2,  

Mitochondria & Bioenergetics ⓘ

EGF↓, 1,   FGFR1↓, 1,   MMP↓, 5,   Raf↓, 1,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 5,   GlucoseCon↓, 1,   lactateProd↓, 1,   LDH↑, 1,   LDHA↓, 1,   NADPH↓, 1,   PKM2↓, 1,  

Cell Death ⓘ

Akt↓, 7,   p‑Akt↓, 1,   Apoptosis↓, 1,   Apoptosis↑, 8,   Bak↑, 1,   BAX↓, 1,   BAX↑, 6,   Bcl-2↓, 3,   Casp10↑, 1,   Casp3↓, 2,   Casp3↑, 4,   Casp8↑, 1,   Casp9↑, 4,   cFLIP↓, 2,   Cyt‑c↑, 4,   Diablo↑, 1,   DR5↓, 1,   DR5↑, 2,   Fas↑, 1,   FasL↑, 1,   iNOS↓, 2,   MAPK↓, 2,   MAPK↑, 1,   MDM2↓, 1,   p27↑, 1,   p38↑, 1,   survivin↓, 2,   TNFR 1↑, 1,   TRAILR↑, 1,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 1,   Sp1/3/4↓, 1,  

Transcription & Epigenetics ⓘ

ac‑H3↑, 1,   ac‑H4↑, 1,   miR-21↑, 1,   other↓, 1,   other↑, 1,   p‑pRB↓, 1,   tumCV↓, 3,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   ER Stress↑, 2,   GRP78/BiP↑, 1,   HSP27↓, 1,   HSP70/HSPA5↓, 2,   HSP90↓, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1,   LC3B-II↑, 1,  

DNA Damage & Repair ⓘ

DFF45↑, 1,   DNAdam↑, 1,   DNMTs↓, 1,   P53↑, 7,   PARP↓, 1,   cl‑PARP↑, 2,   PARP1↑, 1,   PCNA↓, 2,  

Cell Cycle & Senescence ⓘ

CDK1↓, 3,   CDK2↓, 2,   CDK2↑, 1,   CDK4↓, 1,   cycA1/CCNA1↓, 1,   CycB/CCNB1↓, 3,   cycD1/CCND1↓, 4,   cycE/CCNE↓, 1,   P21↑, 1,   TumCCA↑, 7,  

Proliferation, Differentiation & Cell State ⓘ

CSCs↓, 2,   EMT↓, 3,   ERK↓, 2,   ERK↑, 1,   p‑ERK↓, 1,   FGF↓, 1,   GSK‐3β↓, 1,   HDAC↓, 1,   IGF-1R↓, 1,   IGFBP3↑, 1,   mTOR↓, 3,   p‑mTOR↓, 1,   NOTCH↓, 1,   NOTCH1↓, 1,   PI3K↓, 6,   PTEN↑, 1,   RAS↓, 2,   Shh↓, 1,   STAT↓, 1,   STAT3↓, 3,   TOP2↓, 1,   Wnt↓, 1,  

Migration ⓘ

5LO↓, 1,   AntiAg↓, 1,   Ca+2↝, 1,   CLDN2↓, 1,   COL1↓, 1,   COL3A1↓, 1,   CXCL12↓, 1,   E-cadherin↓, 1,   E-cadherin↑, 1,   FAK↓, 1,   Ki-67↓, 1,   KRAS↓, 1,   LEF1↓, 1,   MMP2↓, 4,   MMP7↓, 1,   MMP9↓, 3,   MMPs↓, 4,   N-cadherin↓, 1,   PDGF↓, 1,   PKCδ↓, 2,   Rac1↓, 1,   RAGE↓, 1,   Slug↓, 1,   Snail↓, 2,   TGF-β↓, 3,   TIMP2↑, 1,   TSP-1↑, 3,   TumCMig↓, 1,   TumCP↓, 3,   TumMeta↓, 2,   uPA↓, 2,   uPAR↓, 1,   Vim↓, 2,   β-catenin/ZEB1↓, 2,  

Angiogenesis & Vasculature ⓘ

angioG↓, 2,   EGFR↓, 3,   HIF-1↑, 1,   Hif1a↓, 1,   NO↓, 1,   VEGF↓, 3,   VEGFR2↓, 2,  

Barriers & Transport ⓘ

BBB↑, 1,   GLUT1↓, 1,   P-gp↓, 2,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 4,   CRP↓, 1,   CXCR4↓, 1,   IFN-γ↓, 1,   IKKα↓, 1,   IL10↓, 2,   IL1β↓, 2,   IL6↓, 4,   IL8↓, 1,   Inflam↓, 2,   JAK↓, 1,   NF-kB↓, 3,   TLR4↓, 1,   TNF-α↓, 2,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,   CDK6↓, 2,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 3,   ChemoSen↝, 1,   eff↑, 12,   MDR1↓, 1,   P450↓, 1,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

AR↓, 1,   CRP↓, 1,   EGFR↓, 3,   HER2/EBBR2↓, 1,   IL6↓, 4,   Ki-67↓, 1,   KRAS↓, 1,   LDH↑, 1,   RAGE↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 2,   AntiTum↑, 1,   chemoP↑, 2,  
Total Targets: 195

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

4-HNE↓, 1,   antiOx↓, 2,   antiOx↑, 12,   Catalase↑, 7,   Copper↓, 1,   Fenton↓, 1,   GPx↑, 5,   GSH↑, 8,   H2O2↓, 1,   HO-1↑, 5,   Iron↓, 1,   Keap1↓, 2,   lipid-P↓, 10,   MDA↓, 8,   MDA↑, 1,   MPO↓, 1,   NOX4↓, 1,   NQO1↑, 1,   Nrf1↑, 1,   NRF2↓, 1,   NRF2↑, 10,   ROS↓, 32,   SOD↑, 10,   SOD2↑, 1,   TAC↑, 1,   Trx↑, 1,  

Metal & Cofactor Biology ⓘ

IronCh↓, 1,   IronCh↑, 2,  

Mitochondria & Bioenergetics ⓘ

ATP↑, 1,   MMP↑, 4,  

Core Metabolism/Glycolysis ⓘ

ALDOA↑, 1,   AMP↓, 1,   AMPK↑, 2,   CREB↑, 1,   FASN↓, 1,   GPI↑, 1,   HK2↑, 1,   LDHA↑, 1,   LDL↓, 1,   NADPH↓, 2,   PFKL↑, 1,   PKM1↑, 1,   PKM2↓, 1,   PONs↑, 1,   SIRT1↑, 5,  

Cell Death ⓘ

Akt↓, 1,   Akt↑, 2,   Apoptosis↓, 5,   Bcl-2↓, 1,   Casp12↓, 1,   Casp3↓, 1,   iNOS↓, 5,   p‑JNK↓, 1,   MAPK↓, 2,   MAPK↑, 1,   p38↑, 1,  

Transcription & Epigenetics ⓘ

Ach↑, 1,   other↓, 1,  

Protein Folding & ER Stress ⓘ

ATF6↓, 2,   CHOP↓, 2,   ER Stress↓, 4,   GRP78/BiP↓, 4,   IRE1↓, 1,   PERK↓, 1,  

DNA Damage & Repair ⓘ

P53↝, 1,  

Proliferation, Differentiation & Cell State ⓘ

GSK‐3β↓, 1,   PI3K↓, 1,   PI3K↑, 2,   STAT3?, 1,  

Migration ⓘ

5LO↓, 1,   AntiAg↑, 2,   AP-1↓, 2,   Ca+2↓, 2,   PKCδ↓, 1,   ZO-1↑, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   angioG↑, 1,   CLDN5↑, 1,   EGFR↓, 1,   NO↓, 1,   PDI↓, 1,   VEGF↓, 1,  

Barriers & Transport ⓘ

BBB↑, 2,   BBB↝, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 7,   CRP↓, 1,   HMGB1↓, 2,   ICAM-1↓, 1,   IFN-γ↑, 1,   IKKα↓, 1,   IL10↓, 1,   IL17↓, 1,   IL1β↓, 5,   IL6↓, 6,   IL8↓, 1,   Inflam↓, 17,   JAK2↑, 1,   MCP1↓, 1,   NF-kB↓, 9,   p65↓, 1,   TLR4↑, 1,   TNF-α↓, 7,  

Synaptic & Neurotransmission ⓘ

AChE↓, 3,   BChE↓, 1,   BDNF↑, 1,   tau↓, 1,   p‑tau↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 3,   BACE↓, 1,   NLRP3↓, 2,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 6,   BioAv↝, 1,   Dose↑, 1,   eff↑, 3,   Half-Life↑, 1,  

Clinical Biomarkers ⓘ

BG↓, 1,   BP↓, 3,   CRP↓, 1,   EGFR↓, 1,   IL6↓, 6,  

Functional Outcomes ⓘ

AntiCan↑, 2,   AntiDiabetic↑, 1,   cardioP↑, 7,   cognitive↑, 5,   hepatoP↑, 2,   memory↑, 4,   neuroP↑, 10,   Pain↓, 1,   radioP↑, 1,   RenoP↑, 1,   toxicity↓, 1,  

Infection & Microbiome ⓘ

Bacteria↓, 1,   Sepsis↓, 2,  
Total Targets: 134

Scientific Paper Hit Count for: ROS, Reactive Oxygen Species
39 Quercetin
2 Curcumin
1 Chlorogenic acid
1 EGCG (Epigallocatechin Gallate)
1 Resveratrol
1 2-DeoxyGlucose
1 benzo(a)pyrene
1 Lycopene
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#:275  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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