Resveratrol / RadioS 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


RadioS, RadioSensitizer: Click to Expand ⟱
Source:
Type:
A radiosensitizer is an agent that makes cancer cells more sensitive to the damaging effects of radiation therapy. By using a radiosensitizer, clinicians aim to enhance the effectiveness of radiation treatment by either increasing the damage incurred by tumor cells or by interfering with the cancer cells’ repair mechanisms. This can potentially allow for lower doses of radiation, reduced side effects, or improved treatment outcomes.
Pathways that help Radiosensitivity: downregulating HIF-1α, increase SIRT1, Txr

List of Natural Products with radiosensitizing properties:
-Curcumin:modulate NF-κB, STAT3 and has been shown in preclinical studies to enhance the effects of radiation by inhibiting cell survival pathways.
-Resveratrol:
-EGCG:
-Quercetin:
-Genistein:
-Parthenolide:

How radiosensitizers inhibit the thioredoxin (Trx) system in cellular contexts. Notable radiosensitizers, including:
-gold nanoparticles (GNPs),
-gold triethylphosphine cyanide ([Au(SCN) (PEt3)]),
-auranofin, ceria nanoparticles (CONPs),
-curcumin and its derivatives,
-piperlongamide,
-indolequinone derivatives,
-micheliolide,
-motexafin gadolinium, and
-ethane selenide selenidazole derivatives (SeDs)


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↓,
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↓,
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↓,
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↑,
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↓,
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↓,
5857- RES,  CAP,  Rad,    Resveratrol and capsaicin as safer radiosensitizers for colorectal cancer compared to 5-fluorouracil
- in-vivo, Var, NA
RadioS↑, hepatoP↝, toxicity↓,

Showing Research Papers: 1 to 8 of 8

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 8

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress

Ferroptosis↑, 1,   GPx4↓, 1,   HO-1↑, 1,   lipid-P↑, 1,   ROS↑, 3,   xCT↓, 1,  

Mitochondria & Bioenergetics

ATP↓, 1,   MMP↓, 2,  

Core Metabolism/Glycolysis

AMPK↑, 1,   cMyc↓, 2,   GlutMet↓, 1,   HK2↓, 1,   PFK↓, 1,   POLD1↓, 1,   SIRT1↓, 1,   SIRT1↑, 2,   SIRT2↓, 1,  

Cell Death

Akt↓, 2,   Apoptosis↑, 1,   BAX↑, 1,   Bcl-2↓, 2,   CK2↓, 1,   FasL↓, 1,   Ferroptosis↑, 1,  

Transcription & Epigenetics

tumCV↓, 1,  

Autophagy & Lysosomes

Beclin-1↓, 1,   p62↓, 1,  

DNA Damage & Repair

DNAdam↑, 1,   TP53↑, 1,  

Cell Cycle & Senescence

cycD1/CCND1↓, 1,   P21↑, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State

ALDH↓, 2,   CD44↓, 2,   CSCs↓, 3,   EMT↓, 2,   FOXO4↓, 1,   HH↓, 1,   IGF-1↓, 1,   mTOR↓, 1,   Nanog↓, 1,   Nestin↓, 1,   NOTCH↓, 1,   PI3K↓, 1,   PTEN↑, 2,   Shh↓, 1,   STAT3↓, 2,   TCF↓, 1,   TOP2↓, 1,   Wnt↓, 3,  

Migration

E-cadherin↓, 1,   E-cadherin↑, 2,   Fibronectin↓, 1,   HLA↑, 1,   Ki-67↓, 1,   MALAT1↓, 2,   MMP2↓, 2,   MMP7↓, 1,   MMP9↓, 2,   MMPs↓, 1,   Slug↓, 2,   SMAD2↓, 1,   SMAD3↓, 1,   Snail↓, 1,   TGF-β↓, 1,   TumCI↓, 1,   TumCP↓, 1,   TumMeta↓, 1,   Vim?, 1,   Vim↓, 2,   Zeb1↓, 1,   β-catenin/ZEB1↓, 2,  

Angiogenesis & Vasculature

angioG↓, 2,   Hif1a↓, 3,   VEGF↓, 4,  

Immune & Inflammatory Signaling

COX2↓, 3,   CRP↓, 1,   CXCR4↓, 1,   FOXP3↓, 1,   IL10↓, 1,   IL1β↓, 1,   IL6↓, 2,   NF-kB↓, 3,   p‑NF-kB↓, 1,   PD-1↓, 1,   Th1 response↑, 1,  

Drug Metabolism & Resistance

BioAv↓, 1,   BioAv↑, 1,   ChemoSen↑, 4,   ChemoSen⇅, 1,   Dose↝, 1,   eff↑, 2,   Half-Life↑, 1,   MDR1↓, 1,   P450↓, 1,   RadioS↑, 8,  

Clinical Biomarkers

CRP↓, 1,   IL6↓, 2,   Ki-67↓, 1,   TP53↑, 1,  

Functional Outcomes

cardioP↑, 1,   hepatoP↝, 1,   toxicity↓, 1,  

Infection & Microbiome

CD8+↑, 1,  
Total Targets: 104

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

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

Core Metabolism/Glycolysis

SIRT1↑, 1,  

Angiogenesis & Vasculature

angioG↑, 1,  

Immune & Inflammatory Signaling

Inflam↓, 1,  

Drug Metabolism & Resistance

BioAv↓, 2,   BioAv↑, 2,  

Functional Outcomes

cardioP↑, 1,   memory↑, 1,   neuroP↑, 2,  
Total Targets: 12

Scientific Paper Hit Count for: RadioS, RadioSensitizer
8 Resveratrol
1 Curcumin
1 Sulforaphane (mainly Broccoli)
1 Capsaicin
1 Radiotherapy/Radiation
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#:1107  State#:%  Dir#:%
wNotes=0 sortOrder:rid,rpid

 

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