Database Query Results : Resveratrol, , CSCs

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


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.
Scientific Papers found: Click to Expand⟱
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↓,
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↓, 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↓,
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↓,

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

Results for Effect on Cancer/Diseased Cells:
Akt↓,2,   ALDH↓,1,   ALDH1A1↓,2,   AMPK↑,1,   Apoptosis↑,1,   ATP↓,1,   Bcl-2↓,1,   Beclin-1↓,1,   BNIP3↑,1,   cardioP↑,1,   CD133↓,2,   CD24↓,1,   CD44↓,3,   CD8+↑,1,   ChemoSen↑,1,   ChemoSen⇅,1,   CK2↓,1,   cMyc↓,2,   COX2↓,3,   CRP↓,1,   CSCs↓,5,   CXCR4↓,1,   cycD1↓,1,   DNAdam↑,1,   E-cadherin↑,2,   eff↑,2,   EMT↓,3,   ERK↓,1,   FAK↓,1,   FASN↑,1,   Fibronectin↓,1,   FOXO4↓,1,   GlutMet↓,1,   Hif1a↓,3,   HK2↓,1,   HO-1↑,1,   IGF-1↓,2,   IL1β↓,1,   IL6↓,1,   Inflam↓,1,   ITGB1↓,1,   Ki-67↓,2,   lipid-P↓,1,   MALAT1↓,1,   MDR1↓,1,   MMP↓,2,   MMP2↓,2,   MMP7↓,1,   MMP9↓,4,   mTOR↓,1,   Nanog↓,2,   Nestin↓,1,   NF-kB↓,3,   OCT4↓,1,   P21↑,1,   P450↓,1,   p62↓,1,   PD-1↓,1,   PFK↓,1,   PI3K↓,1,   POLD1↓,1,   PTEN↑,1,   RadioS↑,2,   ROS↑,2,   Shh↓,2,   SIRT1↓,1,   SIRT1↑,1,   SIRT2↓,1,   Slug↓,2,   Smad1↓,1,   SMAD2↓,1,   SMAD3↓,1,   Snail↓,2,   STAT3↓,2,   survivin↓,1,   TCF↓,1,   TGF-β↓,1,   Th1 response↑,1,   TOP2↓,1,   TP53↑,1,   TumCCA↑,1,   TumCI↓,1,   TumCP↓,1,   tumCV↓,2,   TumMeta↓,1,   Twist↓,1,   VEGF↓,3,   Vim?,1,   Vim↓,1,   Wnt↓,1,   Zeb1↓,1,   β-catenin/ZEB1↓,1,  
Total Targets: 92

Results for Effect on Normal Cells:
angioG↑,1,   antiOx↑,2,   BioAv↓,1,   cardioP↑,2,   Inflam↓,1,   Keap1↓,1,   memory↑,1,   neuroP↑,2,   NRF2↑,1,   ROS↓,1,   SIRT1↑,1,  
Total Targets: 11

Scientific Paper Hit Count for: CSCs, Cancer Stem Cells
5 Resveratrol
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:141  Target#:795  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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