Database Query Results : Quercetin, , cycE/CCNE

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


cycE/CCNE, Cyclin E: Click to Expand ⟱
Source:
Type:
Cyclin E regulates multiple downstream molecules, such as the retinoblastoma susceptibility gene (RB1) and the transcription factor E2F.
Cyclin E (Cyclin E1 and Cyclin E2) is the key regulator of the late G1 → S-phase transition.
Cyclin E is a prognostic marker in breast cancer, its altered expression increased with the increasing stage and grade of the tumor.
Cyclin E is a regulatory protein that plays a critical role in the cell cycle, particularly in the transition from the G1 phase to the S phase. Its expression levels can significantly influence cancer progression and patient prognosis.

Cyclin E expression is frequently elevated in various cancers and is generally associated with poor prognosis. Its role in promoting cell cycle progression makes it a potential biomarker for tumor aggressiveness and patient outcomes.


Scientific Papers found: Click to Expand⟱
100- QC,    Inhibition of Prostate Cancer Cell Colony Formation by the Flavonoid Quercetin Correlates with Modulation of Specific Regulatory Genes
- in-vitro, Pca, PC3 - in-vitro, Pca, DU145 - in-vitro, Pca, LNCaP
cycD1/CCND1↓, CCND1, CCND2, CCND3
cycE/CCNE↓, CCNE1, CCNE2
CDK2↓,
CDK4/6↓, CDK4, CDK8
E2Fs↓, E2F2, E2F3
PCNA↓,
cDC2↓,
PTEN↑,
MSH2↑,
P21↑,
EP300↑, p300
BRCA1↑,
NF2↑,
TSC1↑,
TGFβR1↑, TGFβR2
P53↑,
RB1↑, Rb
AKT1↓,
cMyc↓,
CDC7↓,
cycF↓, CCNF
CDC16↓,
CUL4B↑, CUL4B, a member of the cullin gene family that is also known to be involved in control of the cell cycle, was significantly up-regulated by quercetin.
CBP↑,
TSC2↑,
HER2/EBBR2↓, erb-2
BCR↓,
TumCCA↑, quercetin significantly inhibited the expression of specific oncogenes and genes controlling G1, S, G2, and M phases of the cell cycle.
chemoPv↑, Our results correlate with those of nutritional studies that support the roles of dietary bioflavonoids as cancer chemopreventive agents.

58- QC,  doxoR,    Quercetin induces cell cycle arrest and apoptosis in CD133+ cancer stem cells of human colorectal HT29 cancer cell line and enhances anticancer effects of doxorubicin
- in-vitro, CRC, HT-29 - in-vitro, NA, CD133+
Bcl-2↓,
TumCCA↑, Quercetin induces cell cycle arrest and apoptosis in CD133+ cancer stem cells of human colorectal HT29 cancer cell line and enhances anticancer effects of doxorubicin
CD133↓,
CSCs↓,
ChemoSen↑, adding quercetin to Dox chemotherapy is an effective strategy for treatment of both CSCs and bulk tumor cells.
CycB/CCNB1↑, Quer induces G2/M phase accumulation due to enhanced level of the cyclin B and decreased level of the cyclin E, cyclin D, E2F1, and E2F2
cycE/CCNE↓,
cycD1/CCND1↓,
E2Fs↓,

40- QC,    Quercetin arrests G2/M phase and induces caspase-dependent cell death in U937 cells
- in-vitro, lymphoma, U937
cycD1/CCND1↓, dramatic changes in the level of cyclin B, cyclin D, and cyclin E
cycE/CCNE↓,
E2Fs↓,
CycB/CCNB1↑, The G2/M phase accumulation was accompanied by an increase in the level of the cyclin B.
Casp↑, These data clearly indicate that quercetin-induced apoptosis is associated with caspase activation
Apoptosis↑,
TumCCA↑, We report here that quercetin induces anti-proliferation and arrests G2/M phase in U937 cells.
TumCP↓,

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↓, decreasing the levels of CDK2, cyclins E, and D proteins
cycE/CCNE↓,
cycD1/CCND1↓, proteins
ATFs↑, Quercetin also stimulated the protein expression of ATF, GRP78, and GADD153 which is a hall marker of ER stress
GRP78/BiP↑,
Bcl-2↓,
BAX↑, quercetin may induce apoptosis by direct activation of caspase cascade through mitochondrial pathway and ER stress in PC-3 cells.
Casp3↑, Quercetin Promoted the Activations of Caspase-3, -8, and -9 in PC-3 Cells
Casp8↑,
Casp9↑,
ER Stress↑, stress
CHOP↑,
TumCCA↑, quercetin at 150 μM caused G0/G1 phase arrest (31.4-49.7%) and sub-G1 phase cells (19.77%) for 36 h treatment and this effect is a time-dependent manner.
DNAdam↑, incubation with quercetin for 48 h showed an apoptotic cell death and DNA damage
AIF↑, quercetin promoted the trafficking of AIF protein released from mitochondria to nuclei.
Ca+2↑, quercetin-treated PC-3 cells led to the significant changes in Ca 21 concentrations of PC-3 cells from 3 h and up to 12 h [Fig. 4
MMP↓, quercetin significantly decreased the levels of DCm in PC-3 cells in a time-dependent course

3354- QC,    Quercetin: Its Main Pharmacological Activity and Potential Application in Clinical Medicine
- Review, Var, NA
*ROS↓, quercetin is the most effective free radical scavenger in the flavonoid family
*IronCh↓, Chelating metal ions: related studies have confirmed that quercetin can induce Cu2+ and Fe2+ to play an antioxidant role through catechol in its structure.
*lipid-P↓, quercetin could inhibit Fe2+-induced lipid peroxidation by binding Fe2+ a
*GSH↑, regulation of glutathione levels to enhance antioxidant capacity.
*NRF2↑, quercetin upregulates the expression of Nrf2 and nuclear transfer by activating the intracellular p38 MAPK pathway, increasing the level of intracellular GSH
TumCCA↑, human leukaemia U937 cells, quercetin induces cell cycle arrest at G2 (late DNA synthesis phase)
ER Stress↑, quercetin can induce ER stress and promote the release of p53, thereby inhibiting the activities of CDK2, cyclin A, and cyclin B, thereby causing MCF-7 breast cancer cells to stagnate in the S phase.
P53↑,
CDK2↓,
cycA1/CCNA1↓,
CycB/CCNB1↓,
cycE/CCNE↓, downregulation of cyclins E and D, PNCA, and Cdk-2 protein expression and increased expressions of p21 and p27
cycD1/CCND1↓,
PCNA↓,
P21↑,
p27↑,
PI3K↓, quercetin inhibited the PI3K/AKT/mTOR and STAT3 pathways in PEL, which downregulated the expression of survival cell proteins such as c-FLIP, cyclin D1, and cMyc.
Akt↓,
mTOR↓,
STAT3↓, in excess of 20 μM by inhibiting STAT3 signalling
cFLIP↓,
cMyc↓,
survivin↓, Lung cancer [27] ↓ Survivin ↑DR5
DR5↓,
*Inflam↓, Quercetin has been confirmed to be a long-acting anti-inflammatory substance in flavonoids
*IL6↓, inhibit IL-8 is stronger and can inhibit IL-6 and increase cytosolic calcium levels
*IL8↓,
COX2↓, inhibit the enzymes that produce inflammation (cyclooxygenase (COX) and lipoxygenase (LOX))
5LO↓,
*cardioP↑, The protective mechanism of quercetin on the cardiovascular system
*FASN↓, 25 μM, within 30 minutes could inhibit the synthesis of fatty acids.
*AntiAg↑, quercetin helps reduce lipid peroxidation, platelet aggregation, and capillary permeability
*MDA↓, quercetin can decrease the levels of malondialdehyde (MDA)


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 5

Pathway results for Effect on Cancer / Diseased Cells:


Mitochondria & Bioenergetics

AIF↑, 1,   BCR↓, 1,   CDC16↓, 1,   MMP↓, 1,  

Core Metabolism/Glycolysis

AKT1↓, 1,   cMyc↓, 2,  

Cell Death

Akt↓, 1,   Apoptosis↑, 1,   BAX↑, 1,   Bcl-2↓, 2,   Casp↑, 1,   Casp3↑, 1,   Casp8↑, 1,   Casp9↑, 1,   CBP↑, 1,   cFLIP↓, 1,   DR5↓, 1,   p27↑, 1,   survivin↓, 1,  

Kinase & Signal Transduction

CDC7↓, 1,   HER2/EBBR2↓, 1,   TSC2↑, 1,  

Protein Folding & ER Stress

ATFs↑, 1,   CHOP↑, 1,   ER Stress↑, 2,   GRP78/BiP↑, 1,  

DNA Damage & Repair

BRCA1↑, 1,   CUL4B↑, 1,   DNAdam↑, 1,   P53↑, 2,   PCNA↓, 2,  

Cell Cycle & Senescence

CDK2↓, 3,   cycA1/CCNA1↓, 1,   CycB/CCNB1↓, 1,   CycB/CCNB1↑, 2,   cycD1/CCND1↓, 5,   cycE/CCNE↓, 5,   cycF↓, 1,   E2Fs↓, 3,   P21↑, 2,   RB1↑, 1,   TumCCA↑, 5,  

Proliferation, Differentiation & Cell State

CD133↓, 1,   cDC2↓, 1,   CSCs↓, 1,   EP300↑, 1,   mTOR↓, 1,   NF2↑, 1,   PI3K↓, 1,   PTEN↑, 1,   STAT3↓, 1,  

Migration

5LO↓, 1,   Ca+2↑, 1,   CDK4/6↓, 1,   MSH2↑, 1,   TSC1↑, 1,   TumCP↓, 1,  

Immune & Inflammatory Signaling

COX2↓, 1,  

Drug Metabolism & Resistance

ChemoSen↑, 1,  

Clinical Biomarkers

BRCA1↑, 1,   HER2/EBBR2↓, 1,  

Functional Outcomes

chemoPv↑, 1,   TGFβR1↑, 1,  
Total Targets: 63

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

GSH↑, 1,   lipid-P↓, 1,   MDA↓, 1,   NRF2↑, 1,   ROS↓, 1,  

Metal & Cofactor Biology

IronCh↓, 1,  

Core Metabolism/Glycolysis

FASN↓, 1,  

Migration

AntiAg↑, 1,  

Immune & Inflammatory Signaling

IL6↓, 1,   IL8↓, 1,   Inflam↓, 1,  

Clinical Biomarkers

IL6↓, 1,  

Functional Outcomes

cardioP↑, 1,  
Total Targets: 13

Scientific Paper Hit Count for: cycE/CCNE, Cyclin E
5 Quercetin
1 doxorubicin
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#:378  State#:%  Dir#:%
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