Database Query Results : Resveratrol, , HH

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


HH, Hedgehog signaling: Click to Expand ⟱
Source: CGL-CF
Type: HH
Sonic hedgehog, Shh; Indian hedgehog, Ihh; Desert hedgehog, Dhh ; Hh signaling pathway is able to regulate the EMT. Hh signaling-related factors, SHH, SMO and GLI1.
Hedgehog signaling is a crucial pathway in embryonic development and tissue homeostasis, but its dysregulation has been implicated in various cancers. The Hedgehog (Hh) pathway is activated by the binding of Hedgehog ligands (such as Sonic Hedgehog, Indian Hedgehog, and Desert Hedgehog) to their receptors, primarily Patched (PTCH) and Smoothened (SMO).

-Hedgehog pathway is crucial for the maintenance of stem cell populations. When deregulated, it can help sustain cancer stem cells (CSCs) that possess self-renewal properties, drive tumor recurrence, and confer resistance to conventional therapies.

-Inhibitors of the pathway, such as vismodegib and sonidegib, have been developed and are used in clinical settings, particularly for treating advanced BCC and other Hedgehog-dependent tumors.
Scientific Papers found: Click to Expand⟱
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↓,

4667- RES,  CUR,  SFN,    Physiological modulation of cancer stem cells by natural compounds: Insights from preclinical models
- Review, Var, NA
CSCs↓, phytochemicals such as resveratrol, curcumin, sulforaphane, and others suppress CSC-associated pathways as well as sensitize CSCs to chemotherapy and radiotherapy
ChemoSen↑,
RadioS↑,
ALDH↓, deplete ALDH+ or CD44+ CSC pools, which ultimately decrease tumor initiation and recurrence.
CD44↓,
Wnt↓, graphical abstract
β-catenin/ZEB1↓,
NOTCH↓,
HH↓,
NF-kB↓,

101- RES,    Resveratrol inhibits the hedgehog signaling pathway and epithelial-mesenchymal transition and suppresses gastric cancer invasion and metastasis
- in-vitro, GC, SGC-7901
HH↓,
Gli1↓,
EMT↓,
Snail↓,
N-cadherin↓,
E-cadherin↑,

102- RES,    Effect of resveratrol on proliferation and apoptosis of human pancreatic cancer MIA PaCa-2 cells may involve inhibition of the Hedgehog signaling pathway
- in-vitro, PC, MIA PaCa-2
HH↓,
PTCH1↓,
Smo↓,
HH↓, Ihh
EMT↓,
PI3K/Akt↓, thru PI-3K/Akt/NF-κB↓
NF-kB↓,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 4

Results for Effect on Cancer/Diseased Cells:
Akt↓,1,   ALDH↓,1,   ALDH1A1↓,1,   CD133↓,1,   CD44↓,2,   ChemoSen↑,1,   CSCs↓,2,   E-cadherin↑,1,   EMT↓,3,   Gli1↓,2,   GLI2↓,1,   GSK‐3β↝,1,   p‑GSK‐3β↓,1,   HH↓,5,   mTOR↓,1,   N-cadherin↓,2,   NF-kB↓,2,   NOTCH↓,2,   OCT4↓,1,   PI3K↓,1,   PI3K/Akt↓,1,   PTCH1↓,1,   RadioS↑,1,   Shh↓,1,   Smo↓,2,   Snail↓,2,   SOX4↓,1,   Wnt↓,2,   β-catenin/ZEB1↓,2,  
Total Targets: 29

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

Scientific Paper Hit Count for: HH, Hedgehog signaling
4 Resveratrol
1 Curcumin
1 Sulforaphane (mainly Broccoli)
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:141  Target#:141  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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