Database Query Results : Resveratrol, , CD133

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


CD133, prominin-1: Click to Expand ⟱
Source:
Type:
CD133, also known as prominin-1, is a pentaspan transmembrane glycoprotein that is commonly used as a marker for stem cells, particularly in the context of cancer research. It is a cell surface protein that is expressed on the surface of many types of stem cells, including embryonic stem cells, hematopoietic stem cells, and cancer stem cells.

CD133 is often used as a marker to identify and isolate cancer stem cells, which are thought to be responsible for the initiation and progression of cancer.

High levels of CD133 expression have been associated with poor prognosis and reduced overall survival in various types of cancer.
Scientific Papers found: Click to Expand⟱
4701- PTS,  RES,    Targeting cancer stem cells and signaling pathways by resveratrol and pterostilbene
- Review, Var, NA
CSCs↓, Resveratrol and pterostilbene target CSCs
E-cadherin↑, " E-cadherin, # NF-jB, # EMT-associated molecules (Twist1,vimentin)
NF-kB↓,
EMT↓,
GRP78/BiP↓, GRP78
CD133↓, CD133
COX2↓, COX-2,
β-catenin/ZEB1↓,
NOTCH↓, Notch

3081- RES,    Resveratrol and p53: How are they involved in CRC plasticity and apoptosis?
- Review, CRC, NA
NF-kB↓, At 5 µM, resveratrol repressed inflammation (NF-κB), CRC progression (FAK, Ki-67, MMP-9, CXCR4) and CSC production (CD44, CD133, ALDH1).
FAK↓, Inhibition of FAK signaling pathway and thereby attenuation of invasion by resveratrol
Ki-67↓,
MMP9↓,
CSCs↓,
CD44↓,
CD133↓,
ALDH1A1↓,
EMT↓, resveratrol inhibits not only EMT but also enhances CRC cells‘ sensitivity to the standard chemotherapeutic drug 5-FU
ChemoSen↑,
Hif1a↓, Suppression of HIF-1α using β1-integrin receptors through resveratrol, thereby inhibition of inflammation
ITGB1↓,
Inflam↓,

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↓, YI-12 suppress CSCs-related proteins, indicated by decreased expression of CSC-enhancing molecules such as CD133-, OCT4-, and CSC-related protein β-catenin
CD133↓,
OCT4↓,
β-catenin/ZEB1↓,
HER2/EBBR2↓, In conclusion, we highlight the novel resveratrol derivative YI-12 for its ability to inhibit CSCs through the ErbB2 signaling pathway.
TumCP↓, YI-12 Inhibits the Proliferation and Decreases the Colony Formation
PI3K↓, YI-12 Suppresses Human Lung CSCs via the ErbB2-Downregulated PI3K/AKT Pathway
Akt↓,
ALDH1A1↓, YI-12, has been found to enhance the suppression of CSCs such as CD133, ALDH1A1, and OCT4.
eff↑, YI-12 was found to be more potent than its parent compound in terms of both cytotoxicity and selectivity.

4657- RES,    Resveratrol, cancer and cancer stem cells: A review on past to future
- Review, Var, NA
CSCs↓, RSV is reported to regulate all the major CSC signaling pathways, but exact mechanisms of its interactions are not clearly understood
CD133↓, CD133(+) cells ↓
Shh↓, Sonic hedgehog (Shh) ↓
Twist↓, GBM Stem cell marker expression: Twist ↓, Snail↓, Slug ↓, MMP-2 ↓, MMP-9 ↓, Smad ↓
Snail↓,
MMP2↓,
MMP9↓,
Smad1↓,
CD44↓, CSC marker proteins: CD44, CD133, ALDH1A1, Oct-4, Nanog ↓
ALDH1A1↓,
OCT4↓,
Nanog↓,
STAT3↓, STAT3 ↓
survivin↓, Survivin, cyclin D1, Cox-2 and c-Myc ↓
cycD1↓,
COX2↓,
cMyc↓,

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↑, Resveratrol is a natural compound with notable health benefits, such as anti-inflammatory, antioxidant, and chemopreventive properties.
*Inflam↓,
*chemoP↑,
CSCs↓, It has shown potential in inhibiting tumorigenesis and tumour progression via targeted therapy, specifically by targeting cancer stem cells (CSCs)
Wnt↓, Three papers reported on the effects on resveratrol on Wnt/ β-catenin pathway
β-catenin/ZEB1↓,
NOTCH↓, 3 papers on Notch pathway
PI3K↓, 3 papers on PI3K/Akt/mTOR pathway
Akt↓,
mTOR↓,
GSK‐3β↝, Akt/GSK β/snail pathway
Snail↓,
HH↓, 4 papers on Hedgehog pathway
p‑GSK‐3β↓, It downregulated p-AKT, p-GSK3β, Snail and N-cadherin in a dose-dependent manner, indicating its role in modulating the Akt/GSK3β/snail signalling pathway to reverse EMT
N-cadherin↓,
EMT↓,
CD133↓, This further reduced CSC markers CD133, CD44, ALDH1A1, OCT4, SOX2 and β-catenin
CD44↓,
ALDH1A1↓,
OCT4↓,
SOX4↓,
Shh↓, Sun et al., reported that resveratrol downregulated SHH, SMO, Gli1 and Gli2 proteins on renal CSC, reducing the number and size of renal cancer cell spheres and decreasing expression of stemness markers CD44 and CD133
Smo↓,
Gli1↓,
GLI2↓,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 5

Results for Effect on Cancer/Diseased Cells:
Akt↓,2,   ALDH1A1↓,4,   CD133↓,5,   CD44↓,3,   ChemoSen↑,1,   cMyc↓,1,   COX2↓,2,   CSCs↓,5,   cycD1↓,1,   E-cadherin↑,1,   eff↑,1,   EMT↓,3,   FAK↓,1,   Gli1↓,1,   GLI2↓,1,   GRP78/BiP↓,1,   GSK‐3β↝,1,   p‑GSK‐3β↓,1,   HER2/EBBR2↓,1,   HH↓,1,   Hif1a↓,1,   Inflam↓,1,   ITGB1↓,1,   Ki-67↓,1,   MMP2↓,1,   MMP9↓,2,   mTOR↓,1,   N-cadherin↓,1,   Nanog↓,1,   NF-kB↓,2,   NOTCH↓,2,   OCT4↓,3,   PI3K↓,2,   Shh↓,2,   Smad1↓,1,   Smo↓,1,   Snail↓,2,   SOX4↓,1,   STAT3↓,1,   survivin↓,1,   TumCP↓,1,   Twist↓,1,   Wnt↓,1,   β-catenin/ZEB1↓,3,  
Total Targets: 44

Results for Effect on Normal Cells:
antiOx↑,1,   chemoP↑,1,   Inflam↓,1,  
Total Targets: 3

Scientific Paper Hit Count for: CD133, prominin-1
5 Resveratrol
1 Pterostilbene
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:141  Target#:677  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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