Resveratrol / COX2 Cancer Research Results

RES, Resveratrol: Click to Expand ⟱
Features: polyphenol
Found in red grapes and products made with grapes.
Resveratrol is a polyphenol compound found in various plant species, including grapes, berries, and peanuts.
• Anti-inflammatory effects, Antioxidant effects:
- Antiplatelet aggregation for stroke prevention
- BioAvialability use piperine
- some sources may use Japanese knotweed roots (Reynoutria Japonica - root) as source which might contain Emodin (laxative)
-known as Nrf2 activator, both in cancer and normal cells. Which raises controversity of use in ROS↑ therapies. Interestingly there are reports of NRF2↑ and ROS↑ in cancer cells. This raises the question of if it is a chemosensitizer. However other reports indicate NRF2 droping with Res, indicating it maybe a chemosenstizer.
- RES is also considered to be them most effective natural SIRT1↑ -activating compound (STACs).

However, in the presence of certain metals, such as copper or iron, resveratrol can undergo a process called Fenton reaction, which can lead to the generation of reactive oxygen species (ROS). The pro-oxidant effects of resveratrol are often observed at high concentrations, typically above 50-100 μM, and in the presence of certain metals or other pro-oxidant agents. In contrast, the antioxidant effects of resveratrol are typically observed at lower concentrations, typically below 10-20 μM.

Clinical trials have used doses ranging from 150 mg to 5 grams per day. Lower doses (< 1 g/day) are often well-tolerated, but higher doses might be necessary for therapeutic effects and can be associated with side effects.

-Note half-life 1-3 hrs?.
BioAv poor: min 5uM/L required for chemopreventive effects, but 25mg Oral only yeilds 20nM. co-administration of piperine
Pathways:
- usually induce ROS production in cancer cells, while reducing ROS in normal cells.
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓,
- Lowers AntiOxidant defense in Cancer Cells: NRF2(typically increased), TrxR↓**, SOD↓, GSH↓ Catalase↓ HO1↓(wrong direction), GPx↓
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓">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↓, RhoA↓, NF-κB↓, CXCR4↓, SDF1↓, TGF-β↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, EZH2↓, P53↑, HSP↓, Sp proteins↓,
- 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 /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, ECAR↓, OXPHOS↓, GRP78↑, Glucose↓, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, FGF↓, PDGF↓, EGFR↓, Integrins↓,
- inhibits Cancer Stem Cells : CSC↓, CK2↓, Hh↓, CD133↓, CD24↓, β-catenin↓, sox2↓, notch2↓, nestin↓, OCT4↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, ERK↓, JNK,
- 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- & context-dependent) ↓ ROS / buffered Conditional Driver Biphasic redox modulation Resveratrol can act as a pro-oxidant in cancer cells while functioning as an antioxidant in normal cells
2 Mitochondrial integrity / intrinsic apoptosis ↓ ΔΨm; ↑ caspase activation ↔ preserved Driver Execution of intrinsic apoptosis Mitochondrial dysfunction and apoptosis follow ROS elevation in cancer cells
3 SIRT1 / AMPK axis ↑ AMPK; context-dependent SIRT1 modulation ↑ SIRT1 / ↑ AMPK Driver Metabolic stress signaling Resveratrol modulates energy-sensing pathways affecting survival and metabolism
4 PI3K → AKT → mTOR axis ↓ AKT / ↓ mTOR ↔ adaptive suppression Secondary Growth and anabolic inhibition Downregulation of growth signaling contributes to cytostasis and apoptosis sensitization
5 NF-κB signaling ↓ NF-κB activation ↓ inflammatory NF-κB tone Secondary Suppression of survival and inflammatory transcription NF-κB inhibition contributes to reduced proliferation and invasion
6 Cell cycle regulation ↑ G1/S or G2/M arrest ↔ largely spared Phenotypic Cytostatic growth control Cell-cycle arrest reflects upstream signaling disruption
7 HIF-1α / VEGF axis ↓ HIF-1α; ↓ VEGF ↔ minimal Secondary Anti-angiogenic pressure Interference with hypoxia-driven adaptation and angiogenesis


COX2, cycloocygenase-2 (Cox-2) mRNA and Cox-2 protein: Click to Expand ⟱
Source: HalifaxProj(inhibit)
Type:
Cyclooxygenase-2 (COX-2) is an enzyme that plays a critical role in the conversion of arachidonic acid to prostaglandins, which are lipid compounds involved in various physiological processes, including inflammation, pain, and fever. COX-2 is an inducible enzyme, meaning its expression is typically low in normal tissues but can be upregulated in response to inflammatory stimuli, growth factors, and certain oncogenic signals.
-Cyclooxygenase-2 (COX-2), the rate-limiting enzyme in prostaglandin biosynthesis, plays a key role in inflammation and circulatory homeostasis.
-COX-2 is an inducible enzyme that is upregulated in response to pro-inflammatory signals, including cytokines (e.g., IL-1β, TNF-α) and growth factors.

COX-2 is often overexpressed in various tumors, including colorectal, breast, lung, and prostate cancers.
The prostaglandins produced by COX-2, particularly prostaglandin E2 (PGE2), have several effects that can facilitate cancer progression:
Cell Proliferation: PGE2 can promote the proliferation of cancer cells by activating signaling pathways such as the PI3K/Akt and MAPK pathways.
Nonselective NSAIDs, such as aspirin and ibuprofen, inhibit both COX-1 and COX-2. Epidemiological studies have suggested that regular use of NSAIDs may reduce the risk of certain cancers, particularly colorectal cancer.
Drugs specifically targeting COX-2, such as celecoxib, have been developed.

COX-2 and xanthine oxidase are ROS-producing pro-oxidant enzymes that contribute to inflammation. Elevated COX‑2 levels, often found in inflammatory conditions or certain types of cancers, can contribute to increased production of ROS.
Scientific Papers found: Click to Expand⟱
182- CUR,  RES,  GI,    Chemopreventive anti-inflammatory activities of curcumin and other phytochemicals mediated by MAP kinase phosphatase-5 in prostate cells
- in-vitro, Pca, DU145 - in-vitro, Pca, PC3 - in-vitro, Pca, LNCaP - in-vitro, Pca, LAPC-4
p38↓, MKP5↑, TNF-α↓, COX2↓, NF-kB↓,
4701- PTS,  RES,    Targeting cancer stem cells and signaling pathways by resveratrol and pterostilbene
- Review, Var, NA
CSCs↓, E-cadherin↑, NF-kB↓, EMT↓, GRP78/BiP↓, CD133↓, COX2↓, β-catenin/ZEB1↓, NOTCH↓,
3080- RES,    Resveratrol: A miraculous natural compound for diseases treatment
- Review, Var, NA
SIRT1↑, ROCK1↓, AMPK↑, *lipid-P↓, Aβ↓, COX2↓, angioG↓, Hif1a↓, VEGF↓,
3076- RES,    Resveratrol for targeting the tumor microenvironment and its interactions with cancer cells
- Review, Var, NA
IL6↓, MMPs↓, MMP2↓, MMP9↓, BioAv↓, Half-Life↑, BioAv↑, Dose↝, angioG↓, IL10↓, VEGF↓, NF-kB↓, COX2↓, SIRT1↑, Wnt↓, cMyc↓, STAT3↓, PTEN↑, ROS↑, RadioS↑, Hif1a↓, E-cadherin↓, Vim↓, angioG↓,
3079- RES,    Therapeutic role of resveratrol against hepatocellular carcinoma: A review on its molecular mechanisms of action
- Review, Var, NA
angioG↓, TumMeta↓, ChemoSen↑, NADPH↑, SIRT1↑, NF-kB↓, NLRP3↓, Dose↝, COX2↓, MMP9↓, PGE2↓, TIMP1↑, TIMP2↑, Sp1/3/4↓, p‑JNK↓, uPAR↓, ROS↓, CXCR4↓, IL6↓, Gli1↓, *ROS↓, *GSTs↑, *SOD↑, *Catalase↑, *GPx↑, *lipid-P↓, *GSH↑, eff↑, eff↑, eff↑,
3071- RES,    Resveratrol and Its Anticancer Effects
- Review, Var, NA
chemoPv↑, SIRT1↑, Hif1a↓, VEGF↓, STAT3↓, NF-kB↓, COX2↓, PI3K↓, mTOR↓, NRF2↑, NLRP3↓, H2O2↑, ROS↑, P53↑, PUMA↑, BAX↑,
3063- RES,    Resveratrol: A Review of Pre-clinical Studies for Human Cancer Prevention
- Review, Var, NA
*Inflam↓, *antiOx↑, *AntiAg↑, *chemoPv↑, ChemoSen↑, BioAv↑, Half-Life↝, COX2↓, cycD1/CCND1↓, CDK2↓, CDK4↓, CDK6↓, P21↑, MMP9↓, NF-kB↓, Telomerase↓, PSA↓, MAPK↑, P53↑,
3057- RES,    The therapeutic effect of resveratrol: Focusing on the Nrf2 signaling pathway
- Review, Var, NA - Review, AD, NA - Review, Stroke, NA
*NRF2↑, *Keap1↓, *ROS↓, *Apoptosis↓, *Inflam↓, *antiOx↑, *hepatoP↑, *neuroP↑, *cardioP↑, *RenoP↑, *AntiCan↑, *memory↑, *SOD↑, *GPx↑, *Catalase↑, *MDA↓, *NRF2↑, *HO-1↑, *ROS↓, *Aβ↓, *iNOS↓, *COX2↓, *GSH↑, *HO-1⇅, *SIRT1↑,
4657- RES,    Resveratrol, cancer and cancer stem cells: A review on past to future
- Review, Var, NA
CSCs↓, CD133↓, Shh↓, Twist↓, Snail↓, MMP2↓, MMP9↓, Smad1↓, CD44↓, ALDH1A1↓, OCT4↓, Nanog↓, STAT3↓, survivin↓, cycD1/CCND1↓, COX2↓, cMyc↓,
4284- RES,    Resveratrol induces dephosphorylation of Tau by interfering with the MID1-PP2A complex
- in-vitro, AD, HEK293 - NA, Stroke, NA - in-vivo, AD, NA
*p‑tau↓, *PP2A↑, *neuroP↑, *antiOx↑, COX2↓, *AntiAg↑, *SIRT1↑, *AMPK↑, *Acetyl-CoA↓, *FAO↑, *ADAM10↑, *BACE↓, *Aβ↓, *memory↑, *Inflam↓, *ROS↓,
3612- RES,    Resveratrol in Alzheimer's disease: a review of pathophysiology and therapeutic potential
- Review, AD, NA
*other↑, *Aβ↓, *Inflam↓, *NF-kB↓, *neuroP↑, *HO-1↑, *lipid-P↓, *COX2↓, *AMPK↑, *Catalase↑, *SOD↑, *GSR↑, *ROS↓, *MMP9↓, *cognitive↑, *SIRT1↑, *IL1β↓, *IL6↓,
3099- RES,    Resveratrol and cognitive decline: a clinician perspective
- Review, Nor, NA - NA, AD, NA
*antiOx↑, *ROS↓, *cognitive↑, *neuroP↑, *SIRT1↑, *AMPK↑, *GPx↑, *HO-1↑, *GSK‐3β↑, *COX2↓, *PGE2↓, *NF-kB↓, *NO↓, *Casp3↓, *MMP3↓, *MMP9↓, *MMP↑, *GSH↑, *other↑, *BioAv↑, *memory↑, *GlutMet↑, *BioAv↓, *Half-Life↓, *toxicity∅,
3094- RES,    Resveratrol suppresses growth of cancer stem-like cells by inhibiting fatty acid synthase
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
CSCs↓, tumCV↓, FASN↑, BNIP3↑, *cardioP↑, *antiOx↑, NF-kB↓, COX2↓, MMP9↓, IGF-1↓, ERK↓, lipid-P↓, CD24↓,
1489- RES,    Molecular mechanisms of resveratrol as chemo and radiosensitizer in cancer
- Review, Var, NA
RadioS↑, ChemoSen↑, *BioAv↓, *BioAv↑, Ferroptosis↑, lipid-P↑, xCT↓, GPx4↓, *BioAv↑, COX2↓, cycD1/CCND1↓, FasL↓, FOXP3↓, HLA↑, p‑NF-kB↓, BAX↑, Bcl-2↓, MALAT1↓,
3055- RES,    Resveratrol and Tumor Microenvironment: Mechanistic Basis and Therapeutic Targets
- Review, Var, NA
BioAv↓, BioAv↓, Dose↑, eff↑, eff↑, Dose↑, BioAv↑, ROS↑, MMP↓, P21↑, p27↑, TumCCA↑, ChemoSen↑, COX2↓, 5LO↓, VEGF↓, IL1↓, IL6↓, IL8↓, AR↓, PSA↓, MAPK↓, Hif1a↓, Glycolysis↓, miR-21↓, PTEN↑, Half-Life↝, *IGF-1↓, *IGFBP3↑, Half-Life↓,
2441- RES,    Anti-Cancer Properties of Resveratrol: A Focus on Its Impact on Mitochondrial Functions
- Review, Var, NA
*toxicity↓, *BioAv↝, *Dose↝, *hepatoP↑, *neuroP↑, *AntiAg↑, *COX2↓, *antiOx↑, *ROS↓, *ROS↑, PI3K↓, Akt↓, NF-kB↓, Wnt↓, β-catenin/ZEB1↓, NRF2↑, GPx↑, HO-1↑, BioEnh?, PTEN↑, ChemoSen↑, eff↑, mt-ROS↑, Warburg↓, Glycolysis↓, GlucoseCon↓, GLUT1↓, lactateProd↓, HK2↓, EGFR↓, cMyc↓, ROS↝, MMPs↓, MMP7↓, survivin↓, TumCP↓, TumCMig↓, TumCI↓,
2564- RES,    Effect of resveratrol on platelet aggregation by fibrinogen protection
- in-vitro, NA, NA
AntiAg↑, antiOx↓, COX2↓,
2687- RES,    Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs
- Review, NA, NA - Review, AD, NA
NF-kB↓, P450↓, COX2↓, Hif1a↓, VEGF↓, *SIRT1↑, SIRT1↓, SIRT2↓, ChemoSen⇅, cardioP↑, *memory↑, *angioG↑, *neuroP↑, STAT3↓, CSCs↓, RadioS↑, Nestin↓, Nanog↓, TP53↑, P21↑, CXCR4↓, *BioAv↓, EMT↓, Vim↓, Slug↓, E-cadherin↑, AMPK↑, MDR1↓, DNAdam↑, TOP2↓, PTEN↑, Akt↓, Wnt↓, β-catenin/ZEB1↓, cMyc↓, MMP7↓, MALAT1↓, TCF↓, ALDH↓, CD44↓, Shh↓, IL6↓, VEGF↓, eff↑, HK2↓, ROS↑, MMP↓,

Showing Research Papers: 1 to 18 of 18

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 18

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↓, 1,   Ferroptosis↑, 1,   GPx↑, 1,   GPx4↓, 1,   H2O2↑, 1,   HO-1↑, 1,   lipid-P↓, 1,   lipid-P↑, 1,   NRF2↑, 2,   ROS↓, 1,   ROS↑, 4,   ROS↝, 1,   mt-ROS↑, 1,   xCT↓, 1,  

Mitochondria & Bioenergetics ⓘ

MKP5↑, 1,   MMP↓, 2,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 2,   cMyc↓, 4,   FASN↑, 1,   GlucoseCon↓, 1,   Glycolysis↓, 2,   HK2↓, 2,   lactateProd↓, 1,   NADPH↑, 1,   SIRT1↓, 1,   SIRT1↑, 4,   SIRT2↓, 1,   Warburg↓, 1,  

Cell Death ⓘ

Akt↓, 2,   BAX↑, 2,   Bcl-2↓, 1,   FasL↓, 1,   Ferroptosis↑, 1,   p‑JNK↓, 1,   MAPK↓, 1,   MAPK↑, 1,   p27↑, 1,   p38↓, 1,   PUMA↑, 1,   survivin↓, 2,   Telomerase↓, 1,  

Kinase & Signal Transduction ⓘ

Sp1/3/4↓, 1,  

Transcription & Epigenetics ⓘ

miR-21↓, 1,   tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

GRP78/BiP↓, 1,  

Autophagy & Lysosomes ⓘ

BNIP3↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   P53↑, 2,   TP53↑, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 1,   CDK4↓, 1,   cycD1/CCND1↓, 3,   P21↑, 3,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

ALDH↓, 1,   ALDH1A1↓, 1,   CD133↓, 2,   CD24↓, 1,   CD44↓, 2,   CSCs↓, 4,   EMT↓, 2,   ERK↓, 1,   Gli1↓, 1,   IGF-1↓, 1,   mTOR↓, 1,   Nanog↓, 2,   Nestin↓, 1,   NOTCH↓, 1,   OCT4↓, 1,   PI3K↓, 2,   PTEN↑, 4,   Shh↓, 2,   STAT3↓, 4,   TCF↓, 1,   TOP2↓, 1,   Wnt↓, 3,  

Migration ⓘ

5LO↓, 1,   AntiAg↑, 1,   E-cadherin↓, 1,   E-cadherin↑, 2,   HLA↑, 1,   MALAT1↓, 2,   MMP2↓, 2,   MMP7↓, 2,   MMP9↓, 5,   MMPs↓, 2,   ROCK1↓, 1,   Slug↓, 1,   Smad1↓, 1,   Snail↓, 1,   TIMP1↑, 1,   TIMP2↑, 1,   TumCI↓, 1,   TumCMig↓, 1,   TumCP↓, 1,   TumMeta↓, 1,   Twist↓, 1,   uPAR↓, 1,   Vim↓, 2,   β-catenin/ZEB1↓, 3,  

Angiogenesis & Vasculature ⓘ

angioG↓, 4,   EGFR↓, 1,   Hif1a↓, 5,   VEGF↓, 6,  

Barriers & Transport ⓘ

GLUT1↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 14,   CXCR4↓, 2,   FOXP3↓, 1,   IL1↓, 1,   IL10↓, 1,   IL6↓, 4,   IL8↓, 1,   NF-kB↓, 9,   p‑NF-kB↓, 1,   PGE2↓, 1,   PSA↓, 2,   TNF-α↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 1,   NLRP3↓, 2,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,   CDK6↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 3,   BioAv↑, 3,   BioEnh?, 1,   ChemoSen↑, 5,   ChemoSen⇅, 1,   Dose↑, 2,   Dose↝, 2,   eff↑, 7,   Half-Life↓, 1,   Half-Life↑, 1,   Half-Life↝, 2,   MDR1↓, 1,   P450↓, 1,   RadioS↑, 3,  

Clinical Biomarkers ⓘ

AR↓, 1,   EGFR↓, 1,   IL6↓, 4,   PSA↓, 2,   TP53↑, 1,  

Functional Outcomes ⓘ

cardioP↑, 1,   chemoPv↑, 1,  
Total Targets: 142

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 6,   Catalase↑, 3,   GPx↑, 3,   GSH↑, 3,   GSR↑, 1,   GSTs↑, 1,   HO-1↑, 3,   HO-1⇅, 1,   Keap1↓, 1,   lipid-P↓, 3,   MDA↓, 1,   NRF2↑, 2,   ROS↓, 7,   ROS↑, 1,   SOD↑, 3,  

Mitochondria & Bioenergetics ⓘ

MMP↑, 1,  

Core Metabolism/Glycolysis ⓘ

Acetyl-CoA↓, 1,   AMPK↑, 3,   FAO↑, 1,   GlutMet↑, 1,   SIRT1↑, 5,  

Cell Death ⓘ

Apoptosis↓, 1,   Casp3↓, 1,   iNOS↓, 1,  

Transcription & Epigenetics ⓘ

other↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

GSK‐3β↑, 1,   IGF-1↓, 1,   IGFBP3↑, 1,  

Migration ⓘ

AntiAg↑, 3,   MMP3↓, 1,   MMP9↓, 2,  

Angiogenesis & Vasculature ⓘ

angioG↑, 1,   NO↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 4,   IL1β↓, 1,   IL6↓, 1,   Inflam↓, 4,   NF-kB↓, 2,   PGE2↓, 1,  

Synaptic & Neurotransmission ⓘ

ADAM10↑, 1,   p‑tau↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 3,   BACE↓, 1,   PP2A↑, 1,  

Drug Metabolism & Resistance ⓘ

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

Clinical Biomarkers ⓘ

IL6↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   cardioP↑, 2,   chemoPv↑, 1,   cognitive↑, 2,   hepatoP↑, 2,   memory↑, 4,   neuroP↑, 6,   RenoP↑, 1,   toxicity↓, 1,   toxicity∅, 1,  
Total Targets: 60

Scientific Paper Hit Count for: COX2, cycloocygenase-2 (Cox-2) mRNA and Cox-2 protein
18 Resveratrol
1 Curcumin
1 Ginger/6-Shogaol/Gingerol
1 Pterostilbene
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#:141  Target#:66  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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