Resveratrol / P53 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


P53, P53-Guardian of the Genome: Click to Expand ⟱
Source: TCGA
Type: Proapototic
TP53 is the most commonly mutated gene in human cancer. TP53 is a gene that encodes for the p53 tumor suppressor protein ; TP73 (Chr.1p36.33) and TP63 (Chr.3q28) genes that encode transcription factors p73 and p63, respectively, are TP53 homologous structures.
p53 is a crucial tumor suppressor protein that plays a significant role in regulating the cell cycle, maintaining genomic stability, and preventing tumor formation. It is often referred to as the "guardian of the genome" due to its role in protecting cells from DNA damage and stress.
TP53 gene, which encodes the p53 protein, is one of the most frequently mutated genes in human cancers.
Overexpression of MDM2, an inhibitor of p53, can lead to decreased p53 activity even in the presence of wild-type p53.
In some cancers, particularly those with mutant p53, there may be an overexpression of the p53 protein.
Cancers with overexpression: Breast, lung, colorectal, overian, head and neck, Esophageal, bladder, pancreatic, and liver.


Scientific Papers found: Click to Expand⟱
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↑,
3061- RES,    The Anticancer Effects of Resveratrol: Modulation of Transcription Factors
- Review, Var, NA
AhR↓, NRF2↑, *NQO1↑, *HO-1↑, *GSH↑, P53↑, Cyt‑c↑, Diablo↑, Bcl-2↓, Bcl-xL↓, survivin↓, XIAP↓, FOXO↑, p‑PI3K↓, p‑Akt↓, BIM↑, DR4↑, DR5↑, p27↑, cycD1/CCND1↓, SIRT1↑, NF-kB↓, ATF3↑,
2329- RES,    Resveratrol induces apoptosis in human melanoma cell through negatively regulating Erk/PKM2/Bcl-2 axis
- in-vitro, Melanoma, A375
P53↑, Bcl-2↓, BAX↑, Cyt‑c↑, ERK↓, PKM2↓, Apoptosis↑, γH2AX↑, Casp3↑, cl‑PARP1↑,
1490- RES,    Anticancer Potential of Resveratrol, β-Lapachone and Their Analogues
- Review, Var, NA
TumCCA↑, ROS↑, Ca+2↑, MMP↓, ATP↓, TOP1?, P53↑, p53 Wildtype∅, Akt↓, mTOR↓, EMT↓, *BioAv↓,
884- RES,  PTS,    Resveratrol and Pterostilbene Exhibit Anticancer Properties Involving the Downregulation of HPV Oncoprotein E6 in Cervical Cancer Cells
- in-vitro, Cerv, HeLa
TumCD↑, TumCCA↑, E6↓, Casp3↑, P53↑,
882- RES,    Resveratrol: A Double-Edged Sword in Health Benefits
- Review, NA, NA
AntiTum↑, Casp3↑, Casp9↑, BAX↑, Bcl-2↓, Bcl-xL↓, P53↑, NAF1↓, NRF2↑, ROS↑, Apoptosis↑, HDAC↓, TumCCA↑, TumAuto↑, angioG↓, iNOS↓,
2981- RES,    Resveratrol suppresses IGF-1 induced human colon cancer cell proliferation and elevates apoptosis via suppression of IGF-1R/Wnt and activation of p53 signaling pathways
- in-vitro, Colon, HT-29 - in-vitro, Colon, SW48
TumCCA↑, p27↑, cycD1/CCND1↓, TumCP↓, IGF-1R↓, Akt↓, Wnt↓, P53↑, Apoptosis↑, Sp1/3/4↓, cl‑PARP↑, β-catenin/ZEB1↓, MDM2↓,
3054- RES,    Resveratrol induced reactive oxygen species and endoplasmic reticulum stress-mediated apoptosis, and cell cycle arrest in the A375SM malignant melanoma cell line
- in-vitro, Melanoma, A375
TumCG↓, P21↑, p27↑, CycB/CCNB1↓, ROS↑, ER Stress↑, p‑p38↑, P53↑, p‑eIF2α↑, EP4↑, CHOP↑, Bcl-2↓, BAX↓, TumCCA↑, NRF2↓, ChemoSen↑, GSH↓,
4668- RES,    Resveratrol Impedes the Stemness, Epithelial-Mesenchymal Transition, and Metabolic Reprogramming of Cancer Stem Cells in Nasopharyngeal Carcinoma through p53 Activation
- in-vitro, NPC, NA
ROS↑, MMP↓, CSCs↓, P53↑, EMT↓,

Showing Research Papers: 1 to 10 of 10

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 10

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress

ATF3↑, 1,   GSH↓, 1,   H2O2↑, 1,   NAF1↓, 1,   NRF2↓, 1,   NRF2↑, 3,   ROS↑, 5,  

Mitochondria & Bioenergetics

ATP↓, 1,   MMP↓, 2,   XIAP↓, 1,  

Core Metabolism/Glycolysis

PKM2↓, 1,   SIRT1↑, 2,  

Cell Death

AhR↓, 1,   Akt↓, 2,   p‑Akt↓, 1,   Apoptosis↑, 3,   BAX↓, 1,   BAX↑, 3,   Bcl-2↓, 4,   Bcl-xL↓, 2,   BIM↑, 1,   Casp3↑, 3,   Casp9↑, 1,   Cyt‑c↑, 2,   Diablo↑, 1,   DR4↑, 1,   DR5↑, 1,   iNOS↓, 1,   MAPK↑, 1,   MDM2↓, 1,   p27↑, 3,   p‑p38↑, 1,   PUMA↑, 1,   survivin↓, 1,   Telomerase↓, 1,   TumCD↑, 1,  

Kinase & Signal Transduction

Sp1/3/4↓, 1,  

Protein Folding & ER Stress

CHOP↑, 1,   p‑eIF2α↑, 1,   ER Stress↑, 1,  

Autophagy & Lysosomes

TumAuto↑, 1,  

DNA Damage & Repair

P53↑, 10,   p53 Wildtype∅, 1,   cl‑PARP↑, 1,   cl‑PARP1↑, 1,   γH2AX↑, 1,  

Cell Cycle & Senescence

CDK2↓, 1,   CDK4↓, 1,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 3,   P21↑, 2,   TumCCA↑, 5,  

Proliferation, Differentiation & Cell State

CSCs↓, 1,   EMT↓, 2,   EP4↑, 1,   ERK↓, 1,   FOXO↑, 1,   HDAC↓, 1,   IGF-1R↓, 1,   mTOR↓, 2,   PI3K↓, 1,   p‑PI3K↓, 1,   STAT3↓, 1,   TOP1?, 1,   TumCG↓, 1,   Wnt↓, 1,  

Migration

Ca+2↑, 1,   MMP9↓, 1,   TumCP↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature

angioG↓, 1,   Hif1a↓, 1,   VEGF↓, 1,  

Immune & Inflammatory Signaling

COX2↓, 2,   NF-kB↓, 3,   PSA↓, 1,  

Protein Aggregation

NLRP3↓, 1,  

Hormonal & Nuclear Receptors

CDK6↓, 1,  

Drug Metabolism & Resistance

BioAv↑, 1,   ChemoSen↑, 2,   Half-Life↝, 1,  

Clinical Biomarkers

E6↓, 1,   PSA↓, 1,  

Functional Outcomes

AntiTum↑, 1,   chemoPv↑, 1,  
Total Targets: 85

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

antiOx↑, 1,   GSH↑, 1,   HO-1↑, 1,   NQO1↑, 1,  

Migration

AntiAg↑, 1,  

Immune & Inflammatory Signaling

Inflam↓, 1,  

Drug Metabolism & Resistance

BioAv↓, 1,  

Functional Outcomes

chemoPv↑, 1,  
Total Targets: 8

Scientific Paper Hit Count for: P53, P53-Guardian of the Genome
10 Resveratrol
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#:236  State#:%  Dir#:2
wNotes=0 sortOrder:rid,rpid

 

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