condition found tbRes List
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


HDAC, Histone deacetylases: Click to Expand ⟱
Source:
Type:
Enzymes involved in regulating gene expression by removing acetyl groups from histones, the proteins around which DNA is wrapped.
-Many cancers exhibit altered expression levels of HDACs, which can contribute to the dysregulation of genes involved in cell growth, survival, and differentiation.
-HDACs can repress the expression of tumor suppressor genes, leading to uncontrolled cell proliferation and survival. This repression can be a key factor in the development and progression of cancer.
-HDAC inhibitors (HDACi) have been developed and are being investigated for their ability to reactivate silenced genes, induce cell cycle arrest, and promote apoptosis in cancer cells.
-HDAC1, HDAC2): Often overexpressed in various cancers, including breast, prostate, and colorectal cancers. Their overexpression is associated with poor prognosis.
-HDAC4, HDAC5): These may have both oncogenic and tumor-suppressive roles depending on the context and cancer type.
-While HDACs are not classified as traditional oncogenes, their overexpression and activity can contribute to oncogenic processes.
-HDAC inhibitor works by preventing the removal of acetyl groups from histones, thereby modulating gene expression, influencing cell behavior, and potentially reversing aberrant gene silencing seen in various diseases.
-HDAC inhibitors can help reactivate these genes, thereby inhibiting growth and inducing apoptosis in cancer cells.
Scientific Papers found: Click to Expand⟱
3368- QC,    The potential anti-cancer effects of quercetin on blood, prostate and lung cancers: An update
- Review, Var, NA
*Inflam↓, quercetin is known for its anti-inflammatory, antioxidant, and anticancer properties.
*antiOx↑,
*AntiCan↑,
Casp3↓, Quercetin increases apoptosis and autophagy in cancer by activating caspase-3, inhibiting the phosphorylation of Akt, mTOR, and ERK, lessening β-catenin, and stabilizing the stabilization of HIF-1α.
p‑Akt↓,
p‑mTOR↓,
p‑ERK↓,
β-catenin/ZEB1↓,
Hif1a↓,
AntiAg↓, Quercetin have revealed an anti-tumor effect by reducing development of blood vessels. I
VEGFR2↓, decrease tumor growth through targeting VEGFR-2-mediated angiogenesis pathway and suppressing the downstream regulatory component AKT in prostate and breast malignancies.
EMT↓, effects of quercetin on inhibition of EMT, angiogenesis, and invasiveness through the epidermal growth factor receptor (EGFR)/VEGFR-2-mediated pathway in breast cancer
EGFR↓,
MMP2↓, MMP2 and MMP9 are two remarkable compounds in metastatic breast cancer (28–30). quercetin on breast cancer cell lines (MDA-MB-231) and showed that after treatment with this flavonoid, the expression of these two proteinases decreased
MMP↓,
TumMeta↓, head and neck (HNSCC), the inhibitory effect of quercetin on the migration of tumor cells has been shown by regulating the expression of MMPs
MMPs↓,
Akt↓, quercetin by inhibiting the Akt activation pathway dependent on Snail, diminishing the expression of N-cadherin, vimentin, and ADAM9 and raising the expression of E-cadherin and proteins
Snail↓,
N-cadherin↓,
Vim↓,
E-cadherin↑,
STAT3↓, inhibiting STAT3 signaling
TGF-β↓, reducing the expression of TGF-β caused by vimentin and N-cadherin, Twist, Snail, and Slug and increasing the expression of E-cadherin in PC-3 cells.
ROS↓, quercetin exerted an anti-proliferative role on HCC cells by lessening intracellular ROS independently of p53 expression
P53↑, increasing the expression of p53 and BAX in hepatocellular carcinoma (HepG2) cell lines through the reduction of PKC, PI3K, and cyclooxygenase (COX-2)
BAX↑,
PKCδ↓,
PI3K↓,
COX2↓,
cFLIP↓, quercetin by inhibiting PI3K/AKT/mTOR and STAT3 pathways, decreasing the expression of cellular proteins such as c-FLIP, cyclin D1, and c-Myc, as well as reducing the production of IL-6 and IL-10 cytokines, leads to the death of PEL cells
cycD1↓,
cMyc↓,
IL6↓,
IL10↓,
Cyt‑c↑, In addition, quercetin induced c-cytochrome-dependent apoptosis and caspase-3 almost exclusively in the HSB2 cell line
TumCCA↑, Exposure of K562 cells to quercetin also significantly raised the cells in the G2/M phase, which reached a maximum peak in 24 hours
DNMTs↓, pathway through DNA demethylation activity, histone deacetylase (HDAC) repression, and H3ac and H4ac enrichment
HDAC↓,
ac‑H3↑,
ac‑H4↑,
Diablo↑, SMAC/DIABLO exhibited activation
Casp3↑, enhanced levels of activated caspase 3, cleaved caspase 9, and PARP1
Casp9↑,
PARP1↑,
eff↑, green tea and quercetin as monotherapy caused the reduction of levels of anti-apoptotic proteins, CDK6, CDK2, CYCLIN D/E/A, BCL-2, BCL-XL, and MCL-1 and an increase in expression of BAX.
PTEN↑, Quercetin upregulates the level of PTEN as a tumor suppressor, which inhibits AKT signaling
VEGF↓, Quercetin had anti-inflammatory and anti-angiogenesis effects, decreasing VGEF-A, NO, iNOS, and COX-2 levels
NO↓,
iNOS↓,
ChemoSen↑, quercetin and chemotherapy can potentiate their effect on the malignant cell
eff↑, combination with hyperthermia, Shen et al. Quercetin is a method used in cancer treatment by heating, and it was found to reduce Doxorubicin hydrochloride resistance in leukemia cell line K562
eff↑, treatment with ellagic acid, luteolin, and curcumin alone showed excellent anticancer effects.
eff↑, co-treatment with quercetin and curcumin led to a reduction of mitochondrial membrane integrity, promotion of cytochrome C release, and apoptosis induction in CML cells
uPA↓, A-549 cells were shown to have reduced mRNA expressions of urokinase plasminogen activator (uPA), Upar, protein expression of CXCR-4, CXCL-12, SDF-1 when quercetin was applied at 20 and 40 mM/ml by real-time PCR.
CXCR4↓,
CXCL12↓,
CLDN2↓, A-549 cells, indicated that quercetin could reduce mRNA and protein expression of Claudin-2 in A-549 cell lines without involving Akt and ERK1/2,
CDK6↓, CDK6, which supports the growth and viability of various cancer cells, was hampered by the dose-dependent manner of quercetin (IC50 dose of QR for A-549 cells is 52.35 ± 2.44 μM).
MMP9↓, quercetin up-regulated the rates of G1 phase cell cycle and cellular apoptotic in both examined cell lines compared with the control group, while it declined the expressions of the PI3K, AKT, MMP-2, and MMP-9 proteins
TSP-1↑, quercetin increased TSP-1 mRNA and protein expression to inhibit angiogenesis,
Ki-67↓, significant reductions in Ki67 and PCNA proliferation markers and cell survival markers in response to quercetin and/or resveratrol.
PCNA↓,
ROS↑, Also, quercetin effectively causes intracellular ROS production and ER stress
ER Stress↑,

3360- QC,    Role of Flavonoids as Epigenetic Modulators in Cancer Prevention and Therapy
- Review, Var, NA
HDAC↓, Quercetin modulates the expression of various chromatin modifiers and declines the activity of HDACs, DNMTs and HMTs in a dose-dependent manner in human cervical cancer (HeLa) cells
DNMTs↓,
HMTs↓,
Let-7↑, Quercetin also induced let-7c which decreased pancreatic tumor growth by posttranscriptional activation of Numbl and indirect inhibition of Notch
NOTCH↓,

3357- QC,    The polyphenol quercetin induces cell death in leukemia by targeting epigenetic regulators of pro-apoptotic genes
- in-vitro, AML, HL-60 - NA, NA, U937
DNMT1↓, Qu treatment almost eliminates DNMT1 and DNMT3a expression, and this regulation was in part STAT-3 dependent.
DNMT3A↓,
HDAC↓, The treatment also downregulated class I HDACs.
ac‑H3↑, Qu (50 μmol/L) treatment of cell lines for 48 h caused accumulation of acetylated histone 3 and histone 4, resulting in three- to ten fold increases in the promoter region of DAPK1, BCL2L11, BAX, APAF1, BNIP3, and BNIP3L.
ac‑H4↑,
BAX↑,
APAF1↑,
BNIP3↑,
STAT3↑, Quercetin downregulates DNMTs and STAT3

3359- QC,    Quercetin modifies 5′CpG promoter methylation and reactivates various tumor suppressor genes by modulating epigenetic marks in human cervical cancer cells
- in-vitro, Cerv, HeLa
DNMTs↓, When nuclear extracts were incubated with increasing doses of quercetin (25 and 50uM) they were found to inhibit the function of the DNMTs by 32% and 49% respectively, in comparison to untreated control
HDAC↓, quercetin (25 and 50 uM), they were found to inhibit the function of the HDACs by 47% and 62% in comparison to untreated control.
HMTs↓, quercetin (25 and 50 uM), were found to inhibit the function of the HMT H3K9 by 63% and 71%
DNMT3A↓, preferred binding of quercetin on DNMT3A and DNMT3B is within the substrate binding cavity and could competitively inhibit the protein
EZH2↓, Quercetin interacts with EZH2 and functions as an inhibitor
HDAC1↓, Quercetin was able to reduce the activity of class II HDACs significantly, with concomitant downregulation of HDAC1, HDAC2, HDAC6, HDAC7, and HDAC11 expression
HDAC2↓,
HDAC6↓,
HDAC11↓,
G9a↓, quercetin and this correlates well with the observed downregulation of G9A expression
TIMP3↑, Fig8: quercetin resulted in reduced promoter methylation of several TSGs (APC, CDH1, CDH13, DAPK1, FHIT, GSTP1, MGMT, MLH1, PTEN, RARB, RASSF1, SOC51, TIMP3, and VHL
PTEN↑,
SOCS1↑,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 4

Results for Effect on Cancer/Diseased Cells:
Akt↓,1,   p‑Akt↓,1,   AntiAg↓,1,   APAF1↑,1,   BAX↑,2,   BNIP3↑,1,   Casp3↓,1,   Casp3↑,1,   Casp9↑,1,   CDK6↓,1,   cFLIP↓,1,   ChemoSen↑,1,   CLDN2↓,1,   cMyc↓,1,   COX2↓,1,   CXCL12↓,1,   CXCR4↓,1,   cycD1↓,1,   Cyt‑c↑,1,   Diablo↑,1,   DNMT1↓,1,   DNMT3A↓,2,   DNMTs↓,3,   E-cadherin↑,1,   eff↑,4,   EGFR↓,1,   EMT↓,1,   ER Stress↑,1,   p‑ERK↓,1,   EZH2↓,1,   G9a↓,1,   ac‑H3↑,2,   ac‑H4↑,2,   HDAC↓,4,   HDAC1↓,1,   HDAC11↓,1,   HDAC2↓,1,   HDAC6↓,1,   Hif1a↓,1,   HMTs↓,2,   IL10↓,1,   IL6↓,1,   iNOS↓,1,   Ki-67↓,1,   Let-7↑,1,   MMP↓,1,   MMP2↓,1,   MMP9↓,1,   MMPs↓,1,   p‑mTOR↓,1,   N-cadherin↓,1,   NO↓,1,   NOTCH↓,1,   P53↑,1,   PARP1↑,1,   PCNA↓,1,   PI3K↓,1,   PKCδ↓,1,   PTEN↑,2,   ROS↓,1,   ROS↑,1,   Snail↓,1,   SOCS1↑,1,   STAT3↓,1,   STAT3↑,1,   TGF-β↓,1,   TIMP3↑,1,   TSP-1↑,1,   TumCCA↑,1,   TumMeta↓,1,   uPA↓,1,   VEGF↓,1,   VEGFR2↓,1,   Vim↓,1,   β-catenin/ZEB1↓,1,  
Total Targets: 75

Results for Effect on Normal Cells:
AntiCan↑,1,   antiOx↑,1,   Inflam↓,1,  
Total Targets: 3

Scientific Paper Hit Count for: HDAC, Histone deacetylases
4 Quercetin
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:140  Target#:140  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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