Resveratrol / P21 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


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⟱
3088- RES,    Notch signaling mediated repressive effects of resveratrol in inducing caspasedependent apoptosis in MCF-7 breast cancer cells
- in-vitro, BC, MCF-7
NOTCH1↓, BAX↑, CDK4↝, Casp3↑, P21↑,
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↑,
3056- RES,    Less is more for cancer chemoprevention: evidence of a non-linear dose response for the protective effects of resveratrol in humans and mice
- in-vivo, Nor, NA
*AMPK↑, *P21↑, *Dose↓, *chemoPv↑,
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↓,
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↓,
2982- RES,    The flavonoid resveratrol suppresses growth of human malignant pleural mesothelioma cells through direct inhibition of specificity protein 1
- in-vitro, Melanoma, MSTO-211H
tumCV↓, Apoptosis↑, Sp1/3/4↓, p27↓, P21↓, cycD1/CCND1↓, Mcl-1↓, survivin↓,
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 7 of 7

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 7

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress

GSH↓, 1,   NRF2↓, 1,   ROS↑, 3,  

Mitochondria & Bioenergetics

MMP↓, 2,  

Core Metabolism/Glycolysis

AMPK↑, 1,   cMyc↓, 1,   Glycolysis↓, 1,   HK2↓, 1,   SIRT1↓, 1,   SIRT2↓, 1,  

Cell Death

Akt↓, 1,   Apoptosis↑, 1,   BAX↓, 1,   BAX↑, 1,   Bcl-2↓, 1,   Casp3↑, 1,   MAPK↓, 1,   MAPK↑, 1,   Mcl-1↓, 1,   p27↓, 1,   p27↑, 2,   p‑p38↑, 1,   survivin↓, 1,   Telomerase↓, 1,  

Kinase & Signal Transduction

Sp1/3/4↓, 1,  

Transcription & Epigenetics

miR-21↓, 1,   tumCV↓, 1,  

Protein Folding & ER Stress

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

DNA Damage & Repair

DNAdam↑, 1,   P53↑, 2,   TP53↑, 1,  

Cell Cycle & Senescence

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

Proliferation, Differentiation & Cell State

ALDH↓, 1,   CD44↓, 1,   CSCs↓, 1,   EMT↓, 1,   EP4↑, 1,   Nanog↓, 1,   Nestin↓, 1,   NOTCH1↓, 1,   PTEN↑, 2,   Shh↓, 1,   STAT3↓, 1,   TCF↓, 1,   TOP2↓, 1,   TumCG↓, 1,   Wnt↓, 1,  

Migration

5LO↓, 1,   E-cadherin↑, 1,   MALAT1↓, 1,   MMP7↓, 1,   MMP9↓, 1,   Slug↓, 1,   Vim↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature

Hif1a↓, 2,   VEGF↓, 3,  

Immune & Inflammatory Signaling

COX2↓, 3,   CXCR4↓, 1,   IL1↓, 1,   IL6↓, 2,   IL8↓, 1,   NF-kB↓, 2,   PSA↓, 2,  

Hormonal & Nuclear Receptors

AR↓, 1,   CDK6↓, 1,  

Drug Metabolism & Resistance

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

Clinical Biomarkers

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

Functional Outcomes

cardioP↑, 1,  
Total Targets: 91

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

antiOx↑, 1,  

Core Metabolism/Glycolysis

AMPK↑, 1,   SIRT1↑, 1,  

Cell Cycle & Senescence

P21↑, 1,  

Proliferation, Differentiation & Cell State

IGF-1↓, 1,   IGFBP3↑, 1,  

Migration

AntiAg↑, 1,  

Angiogenesis & Vasculature

angioG↑, 1,  

Immune & Inflammatory Signaling

Inflam↓, 1,  

Drug Metabolism & Resistance

BioAv↓, 1,   Dose↓, 1,  

Functional Outcomes

chemoPv↑, 2,   memory↑, 1,   neuroP↑, 1,  
Total Targets: 14

Scientific Paper Hit Count for: P21, P21
7 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#:234  State#:%  Dir#:%
wNotes=0 sortOrder:rid,rpid

 

Home Page