Database Query Results : Resveratrol, , SOX2

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


SOX2, SOX2: Click to Expand ⟱
Source:
Type:
SOX2 is a transcription factor that plays a crucial role in the development and maintenance of various cell types, including stem cells and progenitor cells. In the context of cancer, SOX2 has been found to be overexpressed in several types of tumors, including lung, breast, and esophageal cancers.
Overexpressed in: Lung, Breast, Esophageal, Prostate, GBM, CRC.
Scientific Papers found: Click to Expand⟱
3096- RES,    Identification of potential target genes of non-small cell lung cancer in response to resveratrol treatment by bioinformatics analysis
- in-vitro, Lung, A549 - in-vitro, Lung, H1299
TumCP↓, resveratrol might inhibit proliferation but induce apoptosis and autophagy via inhibiting Akt/mTOR pathway and activating p38-MAPK pathway in A549 and H1299 NSCLC cells [7]
Apoptosis↑,
Akt↓,
mTOR↓,
p38↑,
MAPK↑,
STAT3↓, inhibiting the messenger RNA (mRNA) and protein expression of signal transducer and activator of transcription 3 (STAT3) in A549 cells
ROS↑, by leading to mitochondrial dysfunction and increasing of reactive oxygen species (ROS)
SIRT1↑, suggested that resveratrol inhibited age-dependent spontaneous tumorigenesis by increasing the expression of SIRT1 and activating its downstream targets
SOX2↓, resveratrol treatment promoted EGFR and inhibited SOX2.

3095- RES,    Resveratrol suppresses migration, invasion and stemness of human breast cancer cells by interfering with tumor-stromal cross-talk
- in-vitro, BC, NA
TumCP↓, Resveratrol inhibited proliferation, migration and invasion of human breast cancer cells treated with CAF conditioned media.
TumCMig↓,
TumCI↓,
cycD1/CCND1↓, Resveratrol suppressed the expression of cyclin D1, c-Myc, MMP-2, MMP-9 and Sox-2 in breast cancer cells stimulated with CAFs
cMyc↓,
MMP2↓,
MMP9↓,
SOX2↓,
Akt↓, Resveratrol inhibited activation of Akt and STAT3 induced in human breast cancer cells stimulated with CAF conditioned media.
STAT3↓,
α-SMA↓, resveratrol suppressed the proliferation of liver myofibroblasts through inhibition of α-smooth muscle actin (α-SMA)

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↓, we discovered the CSC-targeting activity of resveratrol (RES) analog moscatilin (MOS)
eff↑, Compared with RES, its analog MOS more effectively inhibited cell viability, colony formation, and induced apoptosis in all lung cancer cell lines (H23, H292, and A549).
Akt↓, MOS exerted its anti-CSC effects by inhibiting Akt and consequently restored the activation of glycogen synthase kinase 3β (GSK-3β) and decreased the pluripotent transcription factors (Sox2 and c-Myc).
GSK‐3β↑,
SOX2↓,
cMyc↓,
TumCCA↑, improved activation of various mechanism, such as cell cycle arrest at G2/M phase, production of ROS-mediated apoptosis, and inhibition of Akt activation.
ROS↑,
Apoptosis↑,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 3

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

ROS↑, 2,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 2,   SIRT1↑, 1,  

Cell Death ⓘ

Akt↓, 3,   Apoptosis↑, 2,   MAPK↑, 1,   p38↑, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

CSCs↓, 1,   GSK‐3β↑, 1,   mTOR↓, 1,   SOX2↓, 3,   STAT3↓, 2,  

Migration ⓘ

MMP2↓, 1,   MMP9↓, 1,   TumCI↓, 1,   TumCMig↓, 1,   TumCP↓, 2,   α-SMA↓, 1,  

Drug Metabolism & Resistance ⓘ

eff↑, 1,  
Total Targets: 21

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: SOX2, SOX2
3 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#:656  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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