Resveratrol / MMP9 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↓, 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


MMP9, MMP9: Click to Expand ⟱
Source: HalifaxProj(suppress)
Type:
Matrix metalloproteinase-9 (MMP-9) is an enzyme that plays a significant role in the degradation of extracellular matrix components.
MMP-9 facilitates the breakdown of the extracellular matrix, which can enable cancer cells to invade surrounding tissues and spread to distant sites (metastasis).
Elevated levels of MMP-9 have been associated with poor prognosis in several cancers, including breast, lung, and colorectal cancers.
MMP2 and MMP9: two enzymes are critical to tumor invasion.
Scientific Papers found: Click to Expand⟱
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↓,
3077- RES,    Resveratrol attenuates matrix metalloproteinase-9 and -2-regulated differentiation of HTB94 chondrosarcoma cells through the p38 kinase and JNK pathways
- in-vitro, Chon, HTB94
MMP2↓, MMP9↓, SOX9↑, MMPs↓, p‑p38↑, p‑JNK↓, NF-kB↓, HO-1↓,
3078- RES,    The Effects of Resveratrol on Prostate Cancer through Targeting the Tumor Microenvironment
- Review, Pca, NA
*ROS↓, ROS↑, DNAdam↑, Apoptosis↑, Hif1a↑, Casp3↑, Casp9↑, Cyt‑c↑, Dose↝, MMPs↓, MMP2↓, MMP9↓, EMT↓, E-cadherin↑, N-cadherin↓, AR↓,
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↑,
3081- RES,    Resveratrol and p53: How are they involved in CRC plasticity and apoptosis?
- Review, CRC, NA
NF-kB↓, FAK↓, Ki-67↓, MMP9↓, CSCs↓, CD44↓, CD133↓, ALDH1A1↓, EMT↓, ChemoSen↑, Hif1a↓, ITGB1↓, Inflam↓,
3083- RES,    Resveratrol suppresses breast cancer cell invasion by inactivating a RhoA/YAP signaling axis
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, MDA-MB-468
YAP/TEAD↓, Rho↓, FAK↓, MMP9↓, ChemoSen↑, RAS↓, ROCK1↓, TumCI↓, TumMeta↓,
3086- RES,    Resveratrol inhibits the tumor migration and invasion by upregulating TET1 and reducing TIMP2/3 methylation in prostate carcinoma cells
- in-vitro, Pca, LNCaP - in-vitro, Pca, PC3 - in-vitro, Pca, DU145
TET1↑, TumCMig↓, TumCI↓, TIMP2↑, TIMP3↑, MMP2↓, MMP9↓,
3089- RES,    The Role of Resveratrol in Cancer Therapy
- Review, Var, NA
angioG↓, VEGF↓, EGFR↓, FGF↑, TumCMig↓, TumCI↓, TIMP1↑, MMP2↓, MMP9↓, NF-kB↓, Hif1a↓, PI3K↓, Akt↓, MAPK↓, EMT↓, AR↓,
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↑,
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↓,
4286- RES,    Neuroprotective Properties of Resveratrol and Its Derivatives—Influence on Potential Mechanisms Leading to the Development of Alzheimer’s Disease
- Review, AD, NA
*neuroP↑, *Inflam↓, *antiOx↑, *GSH↑, *HO-1↑, *iNOS↓, *BDNF↑, *p‑CREB↑, *PKA↑, *Bcl-2↑, *BAX↓, *IL1β↓, *IL6↓, *MMP9↓, *memory↑, *AMPK↑, *PGC-1α↓, *NF-kB↓, *Aβ↓, *SIRT1↑, *p‑tau↓, *PP2A↑, *lipid-P↓, *NLRP3↓, *BACE↓,
3613- RES,    Resveratrol for Alzheimer's disease
- Review, AD, NA
*SIRT1↑, *BioAv↝, *toxicity↓, *ROS↓, *antiOx↑, *Aβ↓, *MMP9↓, *TNF-α↓,
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∅,
3095- RES,    Resveratrol suppresses migration, invasion and stemness of human breast cancer cells by interfering with tumor-stromal cross-talk
- in-vitro, BC, NA
TumCP↓, TumCMig↓, TumCI↓, cycD1/CCND1↓, cMyc↓, MMP2↓, MMP9↓, SOX2↓, Akt↓, STAT3↓, α-SMA↓,
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↓,
3092- RES,    Resveratrol in breast cancer treatment: from cellular effects to molecular mechanisms of action
- Review, BC, MDA-MB-231 - Review, BC, MCF-7
TumCP↓, tumCV↓, TumCI↓, TumMeta↓, *antiOx↑, *cardioP↑, *Inflam↓, *neuroP↑, *Keap1↓, *NRF2↑, *ROS↓, p62↓, IL1β↓, CRP↓, VEGF↓, Bcl-2↓, MMP2↓, MMP9↓, FOXO4↓, POLD1↓, CK2↓, MMP↓, ROS↑, Apoptosis↑, TumCCA↑, Beclin-1↓, Ki-67↓, ATP↓, GlutMet↓, PFK↓, TGF-β↓, SMAD2↓, SMAD3↓, Vim?, Snail↓, Slug↓, E-cadherin↑, EMT↓, Zeb1↓, Fibronectin↓, IGF-1↓, PI3K↓, Akt↓, HO-1↑, eff↑, PD-1↓, CD8+↑, Th1 response↑, CSCs↓, RadioS↑, SIRT1↑, Hif1a↓, mTOR↓,
2566- RES,    A comprehensive review on the neuroprotective potential of resveratrol in ischemic stroke
- Review, Stroke, NA
*neuroP↑, *NRF2↑, *SIRT1↑, *PGC-1α↑, *FOXO↑, *HO-1↑, *NQO1↑, *ROS↓, *BP↓, *BioAv↓, *Half-Life↝, *AMPK↑, *GSK‐3β↓, *eff↑, *AntiAg↑, *BBB↓, *Inflam↓, *MPO↓, *TLR4↓, *NF-kB↓, *p65↓, *MMP9↓, *TNF-α↓, *IL1β↓, *PPARγ↑, *MMP↑, *ATP↑, *Cyt‑c∅, *mt-lipid-P↓, *H2O2↓, *HSP70/HSPA5↝, *Mets↝, *eff↑, *eff↑, *motorD↑, *MDA↓, *NADH:NAD↑, eff↑, eff↑,

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 ⓘ

HO-1↓, 1,   HO-1↑, 1,   lipid-P↓, 1,   ROS↓, 1,   ROS↑, 3,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 1,   MMP↓, 1,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 3,   FASN↑, 1,   GlutMet↓, 1,   NADPH↑, 1,   PFK↓, 1,   POLD1↓, 1,   SIRT1↑, 3,  

Cell Death ⓘ

Akt↓, 3,   Apoptosis↑, 2,   Bcl-2↓, 1,   Casp3↑, 1,   Casp9↑, 1,   CK2↓, 1,   Cyt‑c↑, 1,   p‑JNK↓, 2,   MAPK↓, 1,   MAPK↑, 1,   p‑p38↑, 1,   survivin↓, 1,   Telomerase↓, 1,   YAP/TEAD↓, 1,  

Kinase & Signal Transduction ⓘ

SOX9↑, 1,   Sp1/3/4↓, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 2,  

Autophagy & Lysosomes ⓘ

Beclin-1↓, 1,   BNIP3↑, 1,   p62↓, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   P53↑, 1,  

Cell Cycle & Senescence ⓘ

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

Proliferation, Differentiation & Cell State ⓘ

ALDH1A1↓, 2,   CD133↓, 2,   CD24↓, 1,   CD44↓, 2,   CSCs↓, 4,   EMT↓, 4,   ERK↓, 1,   FGF↑, 1,   FOXO4↓, 1,   Gli1↓, 1,   IGF-1↓, 2,   mTOR↓, 1,   Nanog↓, 1,   OCT4↓, 1,   PI3K↓, 2,   PTEN↑, 1,   RAS↓, 1,   Shh↓, 1,   SOX2↓, 1,   STAT3↓, 3,   Wnt↓, 1,  

Migration ⓘ

E-cadherin↓, 1,   E-cadherin↑, 2,   FAK↓, 2,   Fibronectin↓, 1,   ITGB1↓, 1,   Ki-67↓, 2,   MMP2↓, 8,   MMP9↓, 13,   MMPs↓, 3,   N-cadherin↓, 1,   Rho↓, 1,   ROCK1↓, 1,   Slug↓, 1,   Smad1↓, 1,   SMAD2↓, 1,   SMAD3↓, 1,   Snail↓, 2,   TET1↑, 1,   TGF-β↓, 1,   TIMP1↑, 2,   TIMP2↑, 2,   TIMP3↑, 1,   TumCI↓, 5,   TumCMig↓, 3,   TumCP↓, 2,   TumMeta↓, 3,   Twist↓, 1,   uPAR↓, 1,   Vim?, 1,   Vim↓, 1,   Zeb1↓, 1,   α-SMA↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 4,   EGFR↓, 1,   Hif1a↓, 4,   Hif1a↑, 1,   VEGF↓, 3,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 5,   CRP↓, 1,   CXCR4↓, 1,   IL10↓, 1,   IL1β↓, 1,   IL6↓, 2,   Inflam↓, 1,   NF-kB↓, 7,   PD-1↓, 1,   PGE2↓, 1,   PSA↓, 1,   Th1 response↑, 1,  

Protein Aggregation ⓘ

NLRP3↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 2,   CDK6↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 2,   ChemoSen↑, 4,   Dose↝, 3,   eff↑, 6,   Half-Life↑, 1,   Half-Life↝, 1,   RadioS↑, 2,  

Clinical Biomarkers ⓘ

AR↓, 2,   CRP↓, 1,   EGFR↓, 1,   IL6↓, 2,   Ki-67↓, 2,   PSA↓, 1,  

Infection & Microbiome ⓘ

CD8+↑, 1,  
Total Targets: 129

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 6,   Catalase↑, 2,   GPx↑, 2,   GSH↑, 3,   GSR↑, 1,   GSTs↑, 1,   H2O2↓, 1,   HO-1↑, 4,   Keap1↓, 1,   lipid-P↓, 3,   mt-lipid-P↓, 1,   MDA↓, 1,   Mets↝, 1,   MPO↓, 1,   NQO1↑, 1,   NRF2↑, 2,   ROS↓, 7,   SOD↑, 2,  

Mitochondria & Bioenergetics ⓘ

ATP↑, 1,   MMP↑, 2,   PGC-1α↓, 1,   PGC-1α↑, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 4,   p‑CREB↑, 1,   GlutMet↑, 1,   NADH:NAD↑, 1,   PPARγ↑, 1,   SIRT1↑, 5,  

Cell Death ⓘ

BAX↓, 1,   Bcl-2↑, 1,   Casp3↓, 1,   Cyt‑c∅, 1,   iNOS↓, 1,  

Transcription & Epigenetics ⓘ

other↑, 2,  

Protein Folding & ER Stress ⓘ

HSP70/HSPA5↝, 1,  

Proliferation, Differentiation & Cell State ⓘ

FOXO↑, 1,   GSK‐3β↓, 1,   GSK‐3β↑, 1,  

Migration ⓘ

AntiAg↑, 2,   MMP3↓, 1,   MMP9↓, 5,   PKA↑, 1,  

Angiogenesis & Vasculature ⓘ

NO↓, 1,  

Barriers & Transport ⓘ

BBB↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   IL1β↓, 3,   IL6↓, 2,   Inflam↓, 5,   NF-kB↓, 4,   p65↓, 1,   PGE2↓, 1,   TLR4↓, 1,   TNF-α↓, 2,  

Synaptic & Neurotransmission ⓘ

BDNF↑, 1,   p‑tau↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 3,   BACE↓, 1,   NLRP3↓, 1,   PP2A↑, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   BioAv↑, 1,   BioAv↝, 1,   eff↑, 3,   Half-Life↓, 1,   Half-Life↝, 1,  

Clinical Biomarkers ⓘ

BP↓, 1,   IL6↓, 2,  

Functional Outcomes ⓘ

cardioP↑, 2,   chemoPv↑, 1,   cognitive↑, 2,   memory↑, 2,   motorD↑, 1,   neuroP↑, 5,   toxicity↓, 1,   toxicity∅, 1,  
Total Targets: 75

Scientific Paper Hit Count for: MMP9, MMP9
18 Resveratrol
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#:203  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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