Curcumin / P21 Cancer Research Results

CUR, Curcumin: Click to Expand ⟱
Features:
Curcumin is the main active ingredient in Tumeric. Member of the ginger family.Curcumin is a polyphenol extracted from turmeric with anti-inflammatory and antioxidant properties.
- Has iron-chelating, iron-chelating properties. Ferritin. But still known to increase Iron in Cancer cells.
- GSH depletion in cancer cells, exhaustion of the antioxidant defense system. But still raises GSH↑ in normal cells.
- Higher concentrations (5-10 μM) of curcumin induce autophagy and ROS production
- Inhibition of TrxR, shifting the enzyme from an antioxidant to a prooxidant
- Strong inhibitor of Glo-I, , causes depletion of cellular ATP and GSH
- Curcumin has been found to act as an activator of Nrf2, (maybe bad in cancer cells?), hence could be combined with Nrf2 knockdown
-may suppress CSC: suppresses self-renewal and pathways (Wnt/Notch/Hedgehog).
Clinical studies testing curcumin in cancer patients have used a range of dosages, often between 500 mg and 8 g per day; however, many studies note that doses on the lower end may not achieve sufficient plasma concentrations for a therapeutic anticancer effect in humans.
• Formulations designed to improve curcumin absorption (like curcumin combined with piperine, nanoparticle formulations, or liposomal curcumin) are often employed in clinical trials to enhance its bioavailability.

-Note half-life 6 hrs.
BioAv is poor, use piperine or other enhancers
Pathways:
- induce ROS production at high concentration. Lowers ROS at lower concentrations
curcumin can act as a pro-oxidant when blue light is applied
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓
- Lowers AntiOxidant defense in Cancer Cells: GSH↓ Catalase↓ HO1↓ GPx↓
but conversely is known as a NRF2↑ activator in cancer
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, uPA↓, VEGF↓, NF-κB↓, CXCR4↓, SDF1↓, TGF-β↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMT1↓, DNMT3A↓, EZH2↓, P53↑, HSP↓, Sp proteins↓,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, ERK↓, EMT↓, TOP1↓, TET1↓,
- inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, HK2↓, ECAR↓, OXPHOS↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, FGF↓, PDGF↓, EGFR↓, Integrins↓,
- inhibits Cancer Stem Cells : CSC↓, CK2↓, Hh↓, GLi1↓, CD133↓, CD24↓, β-catenin↓, n-myc↓, sox2↓, OCT4↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK↓, ERK↓, JNK, TrxR**,
- 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 NF-κB signaling ↓ NF-κB activation ↓ inflammatory NF-κB tone Driver Suppression of survival and inflammatory transcription NF-κB is a primary, repeatedly validated curcumin target explaining pleiotropic downstream effects
2 STAT3 signaling ↓ STAT3 phosphorylation / activity ↔ or mild suppression Driver Loss of pro-survival and proliferative signaling STAT3 inhibition contributes to growth arrest, apoptosis sensitization, and reduced cytokine signaling in tumors
3 Reactive oxygen species (ROS) ↑ ROS (dose- & context-dependent) ↓ ROS / buffered Conditional Driver Biphasic redox modulation Curcumin can act as a pro-oxidant in cancer cells with high basal stress while acting antioxidant in normal cells
4 Mitochondrial integrity / intrinsic apoptosis ↓ ΔΨm; ↑ caspase activation ↔ preserved Driver Execution of intrinsic apoptosis Mitochondrial dysfunction and caspase activation occur downstream of NF-κB/STAT3 and ROS effects
5 PI3K → AKT → mTOR axis ↓ AKT / ↓ mTOR ↔ or adaptive suppression Secondary Reduced growth and anabolic signaling AKT/mTOR inhibition contributes to growth suppression and autophagy induction in cancer cells
6 Autophagy ↑ autophagy (protective or pro-death) ↑ adaptive autophagy Secondary Stress adaptation vs cell death Autophagy may be cytoprotective or cooperate with apoptosis depending on context and dose
7 HIF-1α / VEGF hypoxia–angiogenesis axis ↓ HIF-1α; ↓ VEGF ↔ minimal effect Secondary Anti-angiogenic pressure Suppression of hypoxia-driven transcription limits angiogenesis and tumor adaptation
8 Cell cycle regulation ↑ G2/M or G1 arrest ↔ largely spared Phenotypic Cytostatic growth control Cell-cycle arrest reflects upstream signaling and epigenetic effects rather than direct CDK inhibition
9 Migration / invasion (EMT, MMP axis) ↓ migration & invasion ↔ Phenotypic Anti-metastatic phenotype Reduced EMT markers and protease activity limit invasive behavior
10 Epigenetic regulation (p300/CBP HAT activity) ↓ histone acetylation ↔ modest Secondary Transcriptional reprogramming Curcumin modulates chromatin via HAT inhibition rather than classic HDAC inhibition


P21, P21: Click to Expand ⟱
Source:
Type: Proapototic
cyclin-dependent kinase inhibitor p21 (also known as p21 WAF1/Cip1) promotes cell cycle arrest in response to many stimuli.
P21 is a cyclin-dependent kinase inhibitor that plays a crucial role in regulating the cell cycle. It is encoded by the CDKN1A gene and is a key player in the cellular response to stress, including DNA damage.
P21 is often considered a tumor suppressor because its expression is upregulated in response to p53 activation, a well-known tumor suppressor protein. When DNA damage occurs, p53 can activate the transcription of the CDKN1A gene, leading to increased levels of P21, which helps prevent the proliferation of damaged cells.
In many cancers, the p53 pathway is disrupted, leading to decreased levels of P21. p21 is a apoptotic marker protein.
Cell cycle arrest gene p21
Scientific Papers found: Click to Expand⟱
4709- CUR,    Curcumin Regulates Cancer Progression: Focus on ncRNAs and Molecular Signaling Pathways
- Review, Var, NA
miR-21↓, TumCP↓, TumCMig↓, TumCI↓, Apoptosis↑, miR-99↑, JAK↓, STAT↓, cycD1/CCND1↓, P21↑, ChemoSen↑, miR-192-5p↑, cMyc↓, Wnt↓, β-catenin/ZEB1↓, miR-130a↓,
457- CUR,    Curcumin regulates proliferation, autophagy, and apoptosis in gastric cancer cells by affecting PI3K and P53 signaling
- in-vitro, GC, SGC-7901 - in-vitro, GC, BGC-823
TumCP↓, Apoptosis↑, TumAuto↑, P53↑, PI3K↓, P21↑, p‑Akt↓, p‑mTOR↓, Bcl-2↓, Bcl-xL↓, LC3I↓, BAX↑, Beclin-1↑, cl‑Casp3↑, cl‑PARP↑, LC3II↑, ATG3↑, ATG5↑,
454- CUR,    Curcumin-Induced DNA Demethylation in Human Gastric Cancer Cells Is Mediated by the DNA-Damage Response Pathway
- in-vitro, GC, MGC803
TumCMig↓, TumCP↓, ROS↑, mtDam↑, DNAdam↑, Apoptosis↑, ATR↑, P21↑, p‑P53↑, GADD45A↑, p‑γH2AX↑,
1609- CUR,  EA,    Curcumin and Ellagic acid synergistically induce ROS generation, DNA damage, p53 accumulation and apoptosis in HeLa cervical carcinoma cells
- in-vitro, Cerv, NA
eff↑, Dose∅, ROS↑, DNAdam↑, P53↑, P21↑, BAX↑, Dose∅,
477- CUR,    Curcumin induces G2/M arrest and triggers autophagy, ROS generation and cell senescence in cervical cancer cells
- in-vitro, Cerv, SiHa
TumCP↓, TumCCA↑, Apoptosis↑, TumAuto↑, CycB/CCNB1↓, CDC25↓, ROS↑, p62↑, LC3‑Ⅱ/LC3‑Ⅰ↑, cl‑Casp3↑, cl‑PARP↑, P53↑, P21↑,
137- CUR,    Curcumin induces G0/G1 arrest and apoptosis in hormone independent prostate cancer DU-145 cells by down regulating Notch signaling
- in-vitro, Pca, DU145
NOTCH1↓, cycD1/CCND1↓, CDK2↓, P21↑, p27↑, P53↑, Bcl-2↓, Casp3↑, Casp9↑, TumCCA↑, TumCP↓, Apoptosis↑,
14- CUR,    Curcumin, a Dietary Component, Has Anticancer, Chemosensitization, and Radiosensitization Effects by Down-regulating the MDM2 Oncogene through the PI3K/mTOR/ETS2 Pathway
- vitro+vivo, Pca, PC3
PI3K/mTOR/ETS2↓, MDM2↓, P21↑, Apoptosis↑, TumCP↓, eff↑, RadioS↑,
15- CUR,  UA,    Effects of curcumin and ursolic acid in prostate cancer: A systematic review
- Review, Pca, NA
NF-kB↝, Akt↝, AR↝, Apoptosis↝, Bcl-2↝, Casp3↝, BAX↝, P21↝, ROS↝, Bcl-xL↝, JNK↝, MMP2↝, P53↝, PSA↝, VEGF↝, COX2↝, cycD1/CCND1↝, EGFR↝, IL6↝, β-catenin/ZEB1↝, mTOR↝, NRF2↝, AP-1↝, Cyt‑c↝, PI3K↝, PTEN↝, Cyc↝, TNF-α↝,
146- CUR,  EGCG,    Synergistic effect of curcumin on epigallocatechin gallate-induced anticancer action in PC3 prostate cancer cells
- in-vitro, Pca, PC3 - in-vitro, Pca, LNCaP - in-vitro, Pca, DU145
P21↑, TumCCA↑, TumCP↓, BioAv↓,
126- CUR,    Modulation of miR-34a in curcumin-induced antiproliferation of prostate cancer cells
- in-vitro, Pca, 22Rv1 - in-vitro, Pca, PC3 - in-vitro, Pca, DU145
miR-34a↑, β-catenin/ZEB1↓, cMyc↓, P21↑, cycD1/CCND1↓, PCNA↓, TumCG↓,
424- CUR,    Curcumin inhibits autocrine growth hormone-mediated invasion and metastasis by targeting NF-κB signaling and polyamine metabolism in breast cancer cells
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
Src↓, p‑STAT1↓, p‑Akt↓, p‑p44↓, p‑p42↓, RAS↓, Raf↓, Vim↓, β-catenin/ZEB1↓, P53↓, Bcl-2↓, Mcl-1↓, PIAS-3↑, SOCS-3↑, SOCS1↑, ROS↑, NF-kB↓, PAO↑, SSAT↑, P21↑, Bak↑,
425- CUR,    Curcumin inhibits proliferation and promotes apoptosis of breast cancer cells
- in-vitro, BC, T47D - in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231 - in-vitro, BC, MDA-MB-468
CDC25↓, cDC2↓, P21↑, p‑Akt↓, p‑mTOR↓, Bcl-2↓, BAX↑, Casp3↑,
170- CUR,    Curcumin sensitizes TRAIL-resistant xenografts: molecular mechanisms of apoptosis, metastasis and angiogenesis
- vitro+vivo, Pca, PC3
TRAILR↑, BAX↑, P21↑, p27↑, NF-kB↓, cycD1/CCND1↓, VEGF↓, uPA↓, MMP2↓, MMP9↓, Bcl-2↓, Bcl-xL↓,

Showing Research Papers: 1 to 13 of 13

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 13

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

NRF2↝, 1,   PAO↑, 1,   ROS↑, 4,   ROS↝, 1,  

Mitochondria & Bioenergetics ⓘ

CDC25↓, 2,   mtDam↑, 1,   p‑p42↓, 1,   Raf↓, 1,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 2,   PI3K/mTOR/ETS2↓, 1,   SSAT↑, 1,  

Cell Death ⓘ

Akt↝, 1,   p‑Akt↓, 3,   Apoptosis↑, 6,   Apoptosis↝, 1,   Bak↑, 1,   BAX↑, 4,   BAX↝, 1,   Bcl-2↓, 5,   Bcl-2↝, 1,   Bcl-xL↓, 2,   Bcl-xL↝, 1,   Casp3↑, 2,   Casp3↝, 1,   cl‑Casp3↑, 2,   Casp9↑, 1,   Cyt‑c↝, 1,   JNK↝, 1,   Mcl-1↓, 1,   MDM2↓, 1,   p27↑, 2,   TRAILR↑, 1,  

Transcription & Epigenetics ⓘ

miR-192-5p↑, 1,   miR-21↓, 1,  

Autophagy & Lysosomes ⓘ

ATG3↑, 1,   ATG5↑, 1,   Beclin-1↑, 1,   LC3‑Ⅱ/LC3‑Ⅰ↑, 1,   LC3I↓, 1,   LC3II↑, 1,   p62↑, 1,   TumAuto↑, 2,  

DNA Damage & Repair ⓘ

ATR↑, 1,   DNAdam↑, 2,   GADD45A↑, 1,   P53↓, 1,   P53↑, 4,   P53↝, 1,   p‑P53↑, 1,   cl‑PARP↑, 2,   PCNA↓, 1,   p‑γH2AX↑, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 1,   Cyc↝, 1,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 4,   cycD1/CCND1↝, 1,   P21↑, 12,   P21↝, 1,   TumCCA↑, 3,  

Proliferation, Differentiation & Cell State ⓘ

cDC2↓, 1,   miR-34a↑, 1,   miR-99↑, 1,   mTOR↝, 1,   p‑mTOR↓, 2,   NOTCH1↓, 1,   PI3K↓, 1,   PI3K↝, 1,   PIAS-3↑, 1,   PTEN↝, 1,   RAS↓, 1,   Src↓, 1,   STAT↓, 1,   p‑STAT1↓, 1,   TumCG↓, 1,   Wnt↓, 1,  

Migration ⓘ

AP-1↝, 1,   miR-130a↓, 1,   MMP2↓, 1,   MMP2↝, 1,   MMP9↓, 1,   p‑p44↓, 1,   TumCI↓, 1,   TumCMig↓, 2,   TumCP↓, 7,   uPA↓, 1,   Vim↓, 1,   β-catenin/ZEB1↓, 3,   β-catenin/ZEB1↝, 1,  

Angiogenesis & Vasculature ⓘ

EGFR↝, 1,   VEGF↓, 1,   VEGF↝, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↝, 1,   IL6↝, 1,   JAK↓, 1,   NF-kB↓, 2,   NF-kB↝, 1,   PSA↝, 1,   SOCS-3↑, 1,   SOCS1↑, 1,   TNF-α↝, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↝, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   ChemoSen↑, 1,   Dose∅, 2,   eff↑, 2,   RadioS↑, 1,  

Clinical Biomarkers ⓘ

AR↝, 1,   EGFR↝, 1,   IL6↝, 1,   PSA↝, 1,  
Total Targets: 111

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: P21, P21
13 Curcumin
1 Ellagic acid
1 Ursolic acid
1 EGCG (Epigallocatechin Gallate)
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#:65  Target#:234  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

Home Page