Resveratrol / ChemoSen 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


ChemoSen, chemo-sensitization: Click to Expand ⟱
Source:
Type:
The effectiveness of chemotherapy by increasing cancer cell sensitivity to the drugs used to treat them, which is known as “chemo-sensitization”.

Chemo-Sensitizers:
-Curcumin
-Resveratrol
-EGCG
-Quercetin
-Genistein
-Berberine
-Piperine: alkaloid from black pepper
-Ginsenosides: active components of ginseng
-Silymarin
-Allicin
-Lycopene
-Ellagic acid
-caffeic acid phenethyl ester
-flavopiridol
-oleandrin
-ursolic acid
-butein
-betulinic acid
Scientific Papers found: Click to Expand⟱
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↓,
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↑,
102- RES,    Effect of resveratrol on proliferation and apoptosis of human pancreatic cancer MIA PaCa-2 cells may involve inhibition of the Hedgehog signaling pathway
- in-vitro, PC, MIA PaCa-2
HH↓, PTCH1↓, Smo↓, HH↓, EMT↓, PI3K/Akt↓, NF-kB↓, TumCP↓, Apoptosis↑, ChemoSen↑,
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↓,
2334- RES,    Glut 1 in Cancer Cells and the Inhibitory Action of Resveratrol as A Potential Therapeutic Strategy
- Review, Var, NA
GLUT1↓, GlucoseCon↓, lactateProd↓, Akt↓, mTOR↓, Dose↝, SIRT6↑, PKM2↓, HK2↓, PFK1↓, ChemoSen↑,
1492- RES,    Resveratrol: Biological and pharmaceutical properties as anticancer molecule
- Review, Var, NA
RadioS↑, ChemoSen↑,
1491- RES,    Resveratrol Augments Doxorubicin and Cisplatin Chemotherapy: A Novel Therapeutic Strategy
RadioS↑, ChemoSen↑,
2439- RES,    By reducing hexokinase 2, resveratrol induces apoptosis in HCC cells addicted to aerobic glycolysis and inhibits tumor growth in mice
- in-vitro, HCC, HCCLM3 - in-vitro, Nor, L02 - in-vitro, HCC, SMMC-7721 cell - in-vitro, HCC, Bel-7402 - in-vitro, HCC, HUH7
HK2↓, ChemoSen↑, other↑, Glycolysis↓, lactateProd↓, TumCP↓, Casp3↑, cl‑PARP↑, PKM2↓,
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↓,
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↓,
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↓,
2650- RES,    Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical Evidence
- Review, Var, NA
ROS↑, Dose↝, NRF2↑, NAF1↓, ChemoSen↑, BioAv↓,
4667- RES,  CUR,  SFN,    Physiological modulation of cancer stem cells by natural compounds: Insights from preclinical models
- Review, Var, NA
CSCs↓, ChemoSen↑, RadioS↑, ALDH↓, CD44↓, Wnt↓, β-catenin/ZEB1↓, NOTCH↓, HH↓, NF-kB↓,

Showing Research Papers: 1 to 16 of 16

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 16

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Ferroptosis↑, 1,   GPx↑, 1,   GPx4↓, 1,   GSH↓, 1,   HO-1↑, 1,   lipid-P↑, 1,   NAF1↓, 1,   NRF2↓, 1,   NRF2↑, 2,   ROS↓, 1,   ROS↑, 4,   ROS↝, 1,   mt-ROS↑, 1,   xCT↓, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 2,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   cMyc↓, 2,   GlucoseCon↓, 2,   Glycolysis↓, 3,   HK2↓, 4,   lactateProd↓, 3,   NADPH↑, 1,   PFK1↓, 1,   PI3K/Akt↓, 1,   PKM2↓, 2,   SIRT1↓, 1,   SIRT1↑, 1,   SIRT2↓, 1,   Warburg↓, 1,  

Cell Death ⓘ

Akt↓, 3,   Apoptosis↑, 1,   BAX↓, 1,   BAX↑, 1,   Bcl-2↓, 2,   Casp3↑, 1,   FasL↓, 1,   Ferroptosis↑, 1,   p‑JNK↓, 1,   MAPK↓, 1,   MAPK↑, 1,   p27↑, 2,   p‑p38↑, 1,   survivin↓, 1,   Telomerase↓, 1,   YAP/TEAD↓, 1,  

Kinase & Signal Transduction ⓘ

Sp1/3/4↓, 1,  

Transcription & Epigenetics ⓘ

miR-21↓, 1,   other↑, 1,  

Protein Folding & ER Stress ⓘ

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

DNA Damage & Repair ⓘ

DNAdam↑, 1,   P53↑, 2,   cl‑PARP↑, 1,   SIRT6↑, 1,   TP53↑, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 1,   CDK4↓, 1,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 2,   P21↑, 4,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

ALDH↓, 2,   ALDH1A1↓, 1,   CD133↓, 1,   CD44↓, 3,   CSCs↓, 3,   EMT↓, 3,   EP4↑, 1,   Gli1↓, 1,   HH↓, 3,   mTOR↓, 1,   Nanog↓, 1,   Nestin↓, 1,   NOTCH↓, 1,   PI3K↓, 1,   PTCH1↓, 1,   PTEN↑, 3,   RAS↓, 1,   Shh↓, 1,   Smo↓, 1,   STAT3↓, 1,   TCF↓, 1,   TOP2↓, 1,   TumCG↓, 1,   Wnt↓, 3,  

Migration ⓘ

5LO↓, 1,   E-cadherin↑, 1,   FAK↓, 2,   HLA↑, 1,   ITGB1↓, 1,   Ki-67↓, 1,   MALAT1↓, 2,   MMP7↓, 2,   MMP9↓, 4,   MMPs↓, 1,   Rho↓, 1,   ROCK1↓, 1,   Slug↓, 1,   TIMP1↑, 1,   TIMP2↑, 1,   TumCI↓, 2,   TumCMig↓, 1,   TumCP↓, 3,   TumMeta↓, 2,   uPAR↓, 1,   Vim↓, 1,   β-catenin/ZEB1↓, 3,  

Angiogenesis & Vasculature ⓘ

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

Barriers & Transport ⓘ

GLUT1↓, 2,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 5,   CXCR4↓, 2,   FOXP3↓, 1,   IL1↓, 1,   IL6↓, 3,   IL8↓, 1,   Inflam↓, 1,   NF-kB↓, 7,   p‑NF-kB↓, 1,   PGE2↓, 1,   PSA↓, 2,  

Protein Aggregation ⓘ

NLRP3↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,   CDK6↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 3,   BioAv↑, 2,   BioEnh?, 1,   ChemoSen↑, 15,   ChemoSen⇅, 1,   Dose↑, 2,   Dose↝, 3,   eff↑, 7,   Half-Life↓, 1,   Half-Life↝, 2,   MDR1↓, 1,   P450↓, 1,   RadioS↑, 5,  

Clinical Biomarkers ⓘ

AR↓, 1,   EGFR↓, 1,   IL6↓, 3,   Ki-67↓, 1,   PSA↓, 2,   TP53↑, 1,  

Functional Outcomes ⓘ

cardioP↑, 1,  
Total Targets: 147

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   Catalase↑, 1,   GPx↑, 1,   GSH↑, 1,   GSTs↑, 1,   lipid-P↓, 1,   ROS↓, 2,   ROS↑, 1,   SOD↑, 1,  

Core Metabolism/Glycolysis ⓘ

SIRT1↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

IGF-1↓, 1,   IGFBP3↑, 1,  

Migration ⓘ

AntiAg↑, 2,  

Angiogenesis & Vasculature ⓘ

angioG↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   Inflam↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   BioAv↑, 2,   BioAv↝, 1,   Dose↝, 1,  

Functional Outcomes ⓘ

chemoPv↑, 1,   hepatoP↑, 1,   memory↑, 1,   neuroP↑, 2,   toxicity↓, 1,  
Total Targets: 25

Scientific Paper Hit Count for: ChemoSen, chemo-sensitization
16 Resveratrol
1 Curcumin
1 Sulforaphane (mainly Broccoli)
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#:1106  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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