Resveratrol / TumCCA 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


TumCCA, Tumor cell cycle arrest: Click to Expand ⟱
Source:
Type:
Tumor cell cycle arrest refers to the process by which cancer cells stop progressing through the cell cycle, which is the series of phases that a cell goes through to divide and replicate. This arrest can occur at various checkpoints in the cell cycle, including the G1, S, G2, and M phases. S, G1, G2, and M are the four phases of mitosis.


Scientific Papers found: Click to Expand⟱
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↓,
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↓,
993- RES,    Resveratrol reverses the Warburg effect by targeting the pyruvate dehydrogenase complex in colon cancer cells
- in-vitro, CRC, Caco-2 - in-vivo, Nor, HCEC 1CT
TumCG↓, Glycolysis↓, PPP↓, ATP↑, PDH↑, Ca+2↝, TumCP↓, lactateProd↓, OCR↑, ECAR↓, *ECAR∅, *other?, cycE/CCNE↑, cycA1/CCNA1↑, TumCCA↑, cycD1/CCND1↑, OXPHOS↑,
924- RES,    Resveratrol sequentially induces replication and oxidative stresses to drive p53-CXCR2 mediated cellular senescence in cancer cells
- in-vitro, OS, U2OS - in-vitro, Lung, A549
TumCCA↑, ROS↑, γH2AX↑, ATM↑, p‑CHK1↑, cellSen↑, CXCR2↑,
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↑,
883- RES,    Targeting Histone Deacetylases with Natural and Synthetic Agents: An Emerging Anticancer Strategy
HDAC↓, TumCCA↑, Apoptosis↑, angioG↓, ROS↑,
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↓,
881- RES,    Resveratrol inhibits Src and Stat3 signaling and induces the apoptosis of malignant cells containing activated Stat3 protein
- in-vitro, BC, MDA-MB-231 - in-vitro, PC, PANC1 - in-vitro, Pca, DU145
TumCCA↑, cycD1/CCND1↓, Bcl-xL↓, Mcl-1↓, other↓,
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↓,
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↓,
4666- RES,    Structural modification of resveratrol analogue exhibits anticancer activity against lung cancer stem cells via suppression of Akt signaling pathway
- in-vitro, Lung, H23 - in-vitro, Lung, H292 - in-vitro, Lung, A549
CSCs↓, eff↑, Akt↓, GSK‐3β↑, SOX2↓, cMyc↓, TumCCA↑, ROS↑, Apoptosis↑,

Showing Research Papers: 1 to 12 of 12

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 12

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress

GSH↓, 1,   HO-1↑, 1,   NAF1↓, 1,   NRF2↓, 1,   NRF2↑, 1,   OXPHOS↑, 1,   ROS↑, 8,  

Mitochondria & Bioenergetics

ATP↓, 2,   ATP↑, 1,   MMP↓, 3,   OCR↑, 1,  

Core Metabolism/Glycolysis

cMyc↓, 1,   ECAR↓, 1,   GlutMet↓, 1,   Glycolysis↓, 2,   lactateProd↓, 1,   PDH↑, 1,   PFK↓, 1,   POLD1↓, 1,   PPP↓, 1,   SIRT1↑, 1,  

Cell Death

Akt↓, 4,   Apoptosis↑, 5,   BAX↓, 1,   BAX↑, 1,   Bcl-2↓, 3,   Bcl-xL↓, 2,   Casp3↑, 2,   Casp9↑, 1,   CK2↓, 1,   iNOS↓, 1,   MAPK↓, 1,   Mcl-1↓, 1,   MDM2↓, 1,   p27↑, 3,   p‑p38↑, 1,   TumCD↑, 1,  

Kinase & Signal Transduction

Sp1/3/4↓, 1,  

Transcription & Epigenetics

miR-21↓, 1,   other↓, 1,   tumCV↓, 1,  

Protein Folding & ER Stress

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

Autophagy & Lysosomes

Beclin-1↓, 1,   p62↓, 1,   TumAuto↑, 1,  

DNA Damage & Repair

ATM↑, 1,   p‑CHK1↑, 1,   P53↑, 5,   p53 Wildtype∅, 1,   cl‑PARP↑, 1,   γH2AX↑, 1,  

Cell Cycle & Senescence

cycA1/CCNA1↑, 1,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 2,   cycD1/CCND1↑, 1,   cycE/CCNE↑, 1,   P21↑, 2,   TumCCA↑, 12,  

Proliferation, Differentiation & Cell State

CSCs↓, 2,   EMT↓, 2,   EP4↑, 1,   FOXO4↓, 1,   GSK‐3β↑, 1,   HDAC↓, 2,   IGF-1↓, 1,   IGF-1R↓, 1,   mTOR↓, 2,   PI3K↓, 1,   PTEN↑, 1,   SOX2↓, 1,   TOP1?, 1,   TumCG↓, 2,   Wnt↓, 1,  

Migration

5LO↓, 1,   Ca+2↑, 1,   Ca+2↝, 1,   E-cadherin↑, 1,   Fibronectin↓, 1,   Ki-67↓, 1,   MMP2↓, 1,   MMP9↓, 1,   Slug↓, 1,   SMAD2↓, 1,   SMAD3↓, 1,   Snail↓, 1,   TGF-β↓, 1,   TumCI↓, 1,   TumCP↓, 3,   TumMeta↓, 1,   Vim?, 1,   Zeb1↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature

angioG↓, 2,   Hif1a↓, 2,   VEGF↓, 2,  

Immune & Inflammatory Signaling

cellSen↑, 1,   COX2↓, 1,   CRP↓, 1,   CXCR2↑, 1,   IL1↓, 1,   IL1β↓, 1,   IL6↓, 1,   IL8↓, 1,   PD-1↓, 1,   PSA↓, 1,   Th1 response↑, 1,  

Hormonal & Nuclear Receptors

AR↓, 1,  

Drug Metabolism & Resistance

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

Clinical Biomarkers

AR↓, 1,   CRP↓, 1,   E6↓, 1,   IL6↓, 1,   Ki-67↓, 1,   PSA↓, 1,  

Functional Outcomes

AntiTum↑, 1,  

Infection & Microbiome

CD8+↑, 1,  
Total Targets: 125

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

antiOx↑, 1,   Keap1↓, 1,   NRF2↑, 1,   ROS↓, 1,  

Core Metabolism/Glycolysis

ECAR∅, 1,  

Transcription & Epigenetics

other?, 1,  

Proliferation, Differentiation & Cell State

IGF-1↓, 1,   IGFBP3↑, 1,  

Immune & Inflammatory Signaling

Inflam↓, 1,  

Drug Metabolism & Resistance

BioAv↓, 1,  

Functional Outcomes

cardioP↑, 1,   neuroP↑, 1,  
Total Targets: 12

Scientific Paper Hit Count for: TumCCA, Tumor cell cycle arrest
12 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#:322  State#:%  Dir#:%
wNotes=0 sortOrder:rid,rpid

 

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