Resveratrol / CSCs 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


CSCs, Cancer Stem Cells: Click to Expand ⟱
Source:
Type:
Cancer Stem Cells

Phytochemicals (natural plant-derived compounds) that may affect CSCs:
Curcumin
— suppresses self-renewal and pathways (Wnt/Notch/Hedgehog).
Resveratrol
— shown to reduce CSC populations and sphere formation in multiple models.
Sulforaphane (from broccoli sprouts)
— reported to inhibit CSC properties and pathways; active in vitro and in vivo.
EGCG (epigallocatechin-3-gallate, green tea)
— reduces CSC markers and sphere formation in several cancer types.
Quercetin
— reported to inhibit CSC proliferation, self-renewal and invasiveness (breast, endometrial, others).
Berberine
— shown to suppress CSC “stemness” and reduce tumorigenic properties in multiple models.
Genistein (soy isoflavone)
— decreases CSC markers, sphere formation and stemness signaling in prostate/breast/other models.
Honokiol (Magnolia bark)
— shown to eliminate or suppress CSC-like populations in oral, colon, glioma models.
Luteolin
— inhibits stemness/EMT and reduces CSC markers and self-renewal in breast, prostate and other models.
Withaferin A (from Withania somnifera / ashwagandha)
— multiple preclinical reports show WA targets CSCs and reduces tumor growth/metastasis in models.

Circadian disruption in cancer and regulation of cancer stem cells by circadian clock genes: An updated review
Potential Role of the Circadian Clock in the Regulation of Cancer Stem Cells and Cancer Therapy
Can we utilise the circadian clock to target cancer stem cells?
Scientific Papers found: Click to Expand⟱
5397- CUR,  SFN,  RES,  EGCG,  Ash  Targeting Cancer Stem Cells with Phytochemicals: Molecular Mechanisms and Therapeutic Potential
- Review, Var, NA
CSCs↓,
4664- GEN,  CUR,  RES,  EGCG,  SFN  Targeting cancer stem cells by nutraceuticals for cancer therapy
- Review, Var, NA
CSCs↓, other↝, eff↑, CD44↓, p‑STAT3↓,
4701- PTS,  RES,    Targeting cancer stem cells and signaling pathways by resveratrol and pterostilbene
- Review, Var, NA
CSCs↓, E-cadherin↑, NF-kB↓, EMT↓, GRP78/BiP↓, CD133↓, COX2↓, β-catenin/ZEB1↓, NOTCH↓,
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↓,
4663- RES,    Exploring resveratrol’s inhibitory potential on lung cancer stem cells: a scoping review of mechanistic pathways across cancer models
- Review, Var, NA
*antiOx↑, *Inflam↓, *chemoPv↑, CSCs↓, Wnt↓, β-catenin/ZEB1↓, NOTCH↓, PI3K↓, Akt↓, mTOR↓, GSK‐3β↝, Snail↓, HH↓, p‑GSK‐3β↓, N-cadherin↓, EMT↓, CD133↓, CD44↓, ALDH1A1↓, OCT4↓, SOX4↓, Shh↓, Smo↓, Gli1↓, GLI2↓,
4662- RES,    A Promising Resveratrol Analogue Suppresses CSCs in Non-Small-Cell Lung Cancer via Inhibition of the ErbB2 Signaling Pathway
- in-vitro, NSCLC, A549 - in-vitro, NSCLC, H460
CSCs↓, CD133↓, OCT4↓, β-catenin/ZEB1↓, HER2/EBBR2↓, TumCP↓, PI3K↓, Akt↓, ALDH1A1↓, eff↑,
4657- RES,    Resveratrol, cancer and cancer stem cells: A review on past to future
- Review, Var, NA
CSCs↓, CD133↓, Shh↓, Twist↓, Snail↓, MMP2↓, MMP9↓, Smad1↓, CD44↓, ALDH1A1↓, OCT4↓, Nanog↓, STAT3↓, survivin↓, cycD1/CCND1↓, COX2↓, cMyc↓,
3094- RES,    Resveratrol suppresses growth of cancer stem-like cells by inhibiting fatty acid synthase
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
CSCs↓, tumCV↓, FASN↑, BNIP3↑, *cardioP↑, *antiOx↑, NF-kB↓, COX2↓, MMP9↓, IGF-1↓, ERK↓, lipid-P↓, CD24↓,
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↓,
105- RES,  QC,    The Effect of Resveratrol and Quercetin on Epithelial-Mesenchymal Transition in Pancreatic Cancer Stem Cell
- in-vitro, Pca, PANC1
N-cadherin↓, TNF-α↓, ACTA2↓, EMT↓, CD133↓, CSCs↓,
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↓,
4669- RES,    Inhibition of RAD51 by siRNA and Resveratrol Sensitizes Cancer Stem Cells Derived from HeLa Cell Cultures to Apoptosis
- in-vitro, Cerv, NA
RAD51↓, CSCs↓,
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↓,
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 15 of 15

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 15

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

HO-1↑, 1,   lipid-P↓, 1,   ROS↑, 4,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 1,   MMP↓, 3,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   cMyc↓, 3,   FASN↑, 1,   GlutMet↓, 1,   HK2↓, 1,   PFK↓, 1,   POLD1↓, 1,   SIRT1↓, 1,   SIRT1↑, 1,   SIRT2↓, 1,  

Cell Death ⓘ

Akt↓, 5,   Apoptosis↑, 2,   Bcl-2↓, 1,   CK2↓, 1,   survivin↓, 1,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 1,  

Transcription & Epigenetics ⓘ

other↝, 1,   tumCV↓, 2,  

Protein Folding & ER Stress ⓘ

GRP78/BiP↓, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↓, 1,   BNIP3↑, 1,   p62↓, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   P53↑, 1,   RAD51↓, 1,   TP53↑, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 1,   P21↑, 1,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

ALDH↓, 2,   ALDH1A1↓, 4,   CD133↓, 6,   CD24↓, 1,   CD44↓, 6,   CSCs↓, 15,   EMT↓, 7,   ERK↓, 1,   FOXO4↓, 1,   Gli1↓, 1,   GSK‐3β↑, 1,   GSK‐3β↝, 1,   p‑GSK‐3β↓, 1,   HH↓, 2,   IGF-1↓, 2,   mTOR↓, 2,   Nanog↓, 2,   Nestin↓, 1,   NOTCH↓, 3,   OCT4↓, 3,   PI3K↓, 3,   PTEN↑, 1,   Shh↓, 3,   Smo↓, 1,   SOX2↓, 1,   STAT3↓, 2,   p‑STAT3↓, 1,   TCF↓, 1,   TOP2↓, 1,   Wnt↓, 3,  

Migration ⓘ

ACTA2↓, 1,   E-cadherin↑, 3,   FAK↓, 1,   Fibronectin↓, 1,   GLI2↓, 1,   ITGB1↓, 1,   Ki-67↓, 2,   MALAT1↓, 1,   MMP2↓, 2,   MMP7↓, 1,   MMP9↓, 4,   N-cadherin↓, 2,   Slug↓, 2,   Smad1↓, 1,   SMAD2↓, 1,   SMAD3↓, 1,   Snail↓, 3,   SOX4↓, 1,   TGF-β↓, 1,   TumCI↓, 1,   TumCP↓, 2,   TumMeta↓, 1,   Twist↓, 1,   Vim?, 1,   Vim↓, 1,   Zeb1↓, 1,   β-catenin/ZEB1↓, 5,  

Angiogenesis & Vasculature ⓘ

Hif1a↓, 3,   VEGF↓, 3,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 4,   CRP↓, 1,   CXCR4↓, 1,   IL1β↓, 1,   IL6↓, 1,   Inflam↓, 1,   NF-kB↓, 5,   PD-1↓, 1,   Th1 response↑, 1,   TNF-α↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 2,   ChemoSen⇅, 1,   eff↑, 5,   MDR1↓, 1,   P450↓, 1,   RadioS↑, 3,  

Clinical Biomarkers ⓘ

CRP↓, 1,   HER2/EBBR2↓, 1,   IL6↓, 1,   Ki-67↓, 2,   TP53↑, 1,  

Functional Outcomes ⓘ

cardioP↑, 1,  

Infection & Microbiome ⓘ

CD8+↑, 1,  
Total Targets: 116

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 3,   Keap1↓, 1,   NRF2↑, 1,   ROS↓, 1,  

Core Metabolism/Glycolysis ⓘ

SIRT1↑, 1,  

Angiogenesis & Vasculature ⓘ

angioG↑, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 2,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,  

Functional Outcomes ⓘ

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

Scientific Paper Hit Count for: CSCs, Cancer Stem Cells
15 Resveratrol
3 Curcumin
3 Sulforaphane (mainly Broccoli)
2 EGCG (Epigallocatechin Gallate)
1 Ashwagandha(Withaferin A)
1 Genistein (soy isoflavone)
1 Pterostilbene
1 Quercetin
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#:795  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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