condition found tbRes List
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


Sp1/3/4, Specificity Protein: Click to Expand ⟱
Source:
Type:
SP2 (Specificity Protein 2) and SP3 (Specificity Protein 3) are also members of the Sp/KLF (Sp1/Krüppel-like factor) family of transcription factors, similar to SP1. They share some functional similarities but also have distinct roles in cellular processes and cancer biology.
-Sp proteins are a family of transcription factors that play a crucial role in regulating gene expression.
-SP1 is often overexpressed in various types of cancer, including breast, prostate, and lung cancers. However, expression levels of Sp in normal cells and tissues are low to undetectable.

SP inhibitors:
-Curcumin, Resveratrol, EGCG, Genistein, Piperlongumine, Betulinic acid
Scientific Papers found: Click to Expand⟱
2991- RES,  Chemo,    Synergistic anti-cancer effects of resveratrol and chemotherapeutic agent clofarabine against human malignant mesothelioma MSTO-211H cells
- in-vitro, Melanoma, MSTO-211H - in-vitro, Nor, MeT5A
eff↑, resveratrol and clofarabine produced a synergistic antiproliferative effect in MSTO-211H cells, but not in MeT-5A cells.
selectivity↑,
Sp1/3/4↓, ability of resveratrol to reduce the contents of Sp1

2990- RES,    Resveratrol reduces cerebral edema through inhibition of de novo SUR1 expression induced after focal ischemia
- in-vivo, Stroke, NA
*OS↑, We found that RSV reduced the infarct area and cerebral edema, prevented blood-brain barrier damage, improved neurological performance, and increased survival.
*antiOx↑, antioxidant activity of RSV targeted SP transcription factors and inhibited SUR1 and AQP4 expression.
Sp1/3/4↓,

2989- RES,    Resveratrol Represses Pokemon Expression in Human Glioma Cells
- in-vitro, GBM, NA
FBI-1↓, we showed that RSV could efficiently decrease the activity of the Pokemon promoter and the expression of Pokemon.
Sp1/3/4↓, RSV also inhibited Sp1 DNA binding activity to the Pokemon promoter; whereas, it did not influence the expression and nuclear translocation of Sp1.

2988- RES,    The Antimetastatic Effects of Resveratrol on Hepatocellular Carcinoma through the Downregulation of a Metastasis-Associated Protease by SP-1 Modulation
- in-vitro, HCC, HUH7
TumCMig↓, resveratrol treatment significantly inhibited cell migration and invasion capacities of Huh7 cell lines that have low cytotoxicity in vitro, even at a high concentration of 100 µM.
TumCI↓,
uPA↓, activities and protein levels of the urokinase-type plasminogen activator (u-PA) were inhibited by resveratrol.
Sp1/3/4↓, reactive in transcription protein of nuclear factor SP-1 was inhibited by resveratrol.

2987- RES,    Resveratrol ameliorates myocardial damage by inducing vascular endothelial growth factor-angiogenesis and tyrosine kinase receptor Flk-1
- in-vivo, Nor, NA
*VEGF↑, effect of resveratrol on significant upregulation of the protein expression profiles of vascular endothelial growth factor (VEGF) and its tyrosine kinase receptor Flk-1, 3 wk after MI.
*iNOS↑, Pretreatment with resveratrol also increased nitric-oxide synthase (inducible NOS and endothelial NOS) along with increased antiapoptotic and proangiogenic factors nuclear factor (NF)-kappaB and specificity protein (SP)-1.
*NF-kB↑,
*Sp1/3/4↑,
*cardioP↑, demonstrate increased capillary density as well as improved left ventricular function by pharmacological preconditioning with resveratrol 3 wk after MI

2986- RES,    Effect of the natural compound trans‑resveratrol on human MCM4 gene transcription
- in-vitro, Cerv, HeLa - in-vitro, AML, HL-60
Sp1/3/4↑, As revealed in Fig. 5A, an increase of Sp1 and a decrease of PU.1 were observed. The Sp1/PU.1 ratio was markedly induced 24 h after the addition of Rsv to the culture medium

3079- RES,    Therapeutic role of resveratrol against hepatocellular carcinoma: A review on its molecular mechanisms of action
- Review, Var, NA
angioG↓, Resveratrol suppresses angiogenesis and metastatic markers to reverse cancer spread.
TumMeta↓,
ChemoSen↑, Resveratrol chemosensitizes chemotherapy and synergizes anti-cancer phytochemicals.
NADPH↑, Both in vitro and in vivo studies indicates that resveratrol enhances various redox enzymes activity, especially nicotinamide adenine dinucleotide phosphate (NADPH)
SIRT1↑, resveratrol effectively modulates both the cytokine and chemokine profiles in immune and endothelial cells by the upregulation of sirtuin-1 (SIRT1)
NF-kB↓, suppression of NF-κB and prevention of the activation of NOD-like receptor family (Nrf) pyrin domain containing-3 inflammasome [
NLRP3↓,
Dose↝, The optimal dose of resveratrol being around 150 mg per day is considered safe by all means.
COX2↓, Cox2 ↓; MMP9 ↓
MMP9↓,
PGE2↓, Cox1 and 2; PGE2↓
TIMP1↑, Resveratrol suppresses the PMA-induced MMP activity in HepG2 cell line, while it also upregulates tissue inhibitor proteins of MMP, namely, TIMP1 and TIMP2, in dose-dependent manner
TIMP2↑,
Sp1/3/4↓, Resveratrol mitigates the expression of SP-1 by inhibiting both phosphorylation of JNK1/2 and expression of urokinase-type plasminogen activator in Huh-7 cell line
p‑JNK↓,
uPAR↓,
ROS↓, Resveratrol attenuates the excessive ROS production and inflammatory cytokine, IL-6, and CXCR4 receptor expression by downregulating Gli-1 expression.
CXCR4↓,
IL6↓,
Gli1↓,
*ROS↓, redox imbalance may be attenuated by resveratrol via downregulating ROS production and simultaneously inducing antioxidant enzymes, GST, SOD, CAT and GPx activities in the cells
*GSTs↑,
*SOD↑,
*Catalase↑,
*GPx↑,
*lipid-P↓, [72] observed that resveratrol treatment not only reduces lipid peroxidation but also increases GSH and GST serum levels in CCl4-treated rats as compared to the CCl4-control animals
*GSH↑,
eff↑, Resveratrol, in combination with thymoquinone (TQ), has been demonstrated to provide a synergistic antiproliferative efficacy against HCC cell lines as reported by Ismail et al.
eff↑, Curcumin, a potential anticancer phytochemical, in combination with resveratrol has been reported to trigger synergistic apoptotic effects against Hepa1–6 cells
eff↑, berberine in combination with resveratrol lowers the cell viability and cell adhesion. At low concentration, berberine significantly induces cell death while resveratrol inhibits cell migration in HepG2 cells

2984- RES,    Involvement of miR-539-5p in the inhibition of de novo lipogenesis induced by resveratrol in white adipose tissue
- in-vivo, Nor, NA
*Sp1/3/4↓, Among the three targets, only SP1 showed a reduction in protein expression.
*SREBP1↓, In addition, significant reductions in SREBP1 protein expression and fasn gene expression were found in resveratrol-treated rats.
*FASN↓,

104- RES,  QC,    Resveratrol and Quercetin in Combination Have Anticancer Activity in Colon Cancer Cells and Repress Oncogenic microRNA-27a
- in-vitro, Colon, HT-29
Casp3↑, x2
PARP↑,
survivin↓,
miR-27a-3p↓, miR-27a
Sp1/3/4↓,
ZBTB10↑,

2985- RES,    Resveratrol Inhibits Diabetic-Induced Müller Cells Apoptosis through MicroRNA-29b/Specificity Protein 1 Pathway
- in-vivo, Nor, NA - vitro+vivo, Diabetic, NA
*Sp1/3/4↓, diabetes-induced downregulated expression of miR-29b and upregulated expression of SP1 could be rescued by RSV in vivo and in vitro
*miR-29b↑,

2983- RES,    Resveratrol Improves Diabetic Retinopathy via Regulating MicroRNA-29b/Specificity Protein 1/Apoptosis Pathway by Enhancing Autophagy
- in-vitro, Nor, NA
*Beclin-1↑, RSV increased autophagosome formation and LC3-I/LC3-II and Beclin-1 levels while decreasing P62 level, thereby promoting autophagy and inhibiting dysregulation of miR-29b/SP1 pathway expression and RMCs apoptosis in DR rat retinal tissues and high gl
*p62↓,
*Sp1/3/4↓, RSV further inhibits the apoptosis of RMCs by activating autophagy and regulating the early miR-29b downregulation and SP1 upregulation induced by high glucose
*Apoptosis↓,

2982- RES,    The flavonoid resveratrol suppresses growth of human malignant pleural mesothelioma cells through direct inhibition of specificity protein 1
- in-vitro, Melanoma, MSTO-211H
tumCV↓, Cell viability was decreased and apoptotic cell death was increased by Res (0-60 µM).
Apoptosis↑,
Sp1/3/4↓, significantly suppressed Sp1 protein levels, but not Sp1 mRNA levels
p27↓, figure 4
P21↓,
cycD1↓,
Mcl-1↓,
survivin↓,

2981- RES,    Resveratrol suppresses IGF-1 induced human colon cancer cell proliferation and elevates apoptosis via suppression of IGF-1R/Wnt and activation of p53 signaling pathways
- in-vitro, Colon, HT-29 - in-vitro, Colon, SW48
TumCCA↑, by arresting G0/G1-S phase cell cycle progression through p27 stimulation and cyclin D1 suppression.
p27↑,
cycD1↓,
TumCP↓, resveratrol suppressed IGF-1R protein levels and concurrently attenuated the downstream Akt/Wnt signaling pathways that play a critical role in cell proliferation.
IGF-1R↓,
Akt↓,
Wnt↓,
P53↑, Resveratrol treatment induced apoptosis by activating tumor suppressor p53 protein,
Apoptosis↑,
Sp1/3/4↓, Resveratrol also activated p53 protein and suppressed levels of sp1, a protein that transcriptionally activates IGF-1R
cl‑PARP↑, Resveratrol treatment elevated cleaved PARP, a hallmark of apoptosis
β-catenin/ZEB1↓, lower levels of nuclear β-catenin in resveratrol treated cells
MDM2↓, resveratrol activates p53 and suppresses MDM2 levels in colon cancer cells


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 13

Results for Effect on Cancer/Diseased Cells:
Akt↓,1,   angioG↓,1,   Apoptosis↑,2,   Casp3↑,1,   ChemoSen↑,1,   COX2↓,1,   CXCR4↓,1,   cycD1↓,2,   Dose↝,1,   eff↑,4,   FBI-1↓,1,   Gli1↓,1,   IGF-1R↓,1,   IL6↓,1,   p‑JNK↓,1,   Mcl-1↓,1,   MDM2↓,1,   miR-27a-3p↓,1,   MMP9↓,1,   NADPH↑,1,   NF-kB↓,1,   NLRP3↓,1,   P21↓,1,   p27↓,1,   p27↑,1,   P53↑,1,   PARP↑,1,   cl‑PARP↑,1,   PGE2↓,1,   ROS↓,1,   selectivity↑,1,   SIRT1↑,1,   Sp1/3/4↓,8,   Sp1/3/4↑,1,   survivin↓,2,   TIMP1↑,1,   TIMP2↑,1,   TumCCA↑,1,   TumCI↓,1,   TumCMig↓,1,   TumCP↓,1,   tumCV↓,1,   TumMeta↓,1,   uPA↓,1,   uPAR↓,1,   Wnt↓,1,   ZBTB10↑,1,   β-catenin/ZEB1↓,1,  
Total Targets: 48

Results for Effect on Normal Cells:
antiOx↑,1,   Apoptosis↓,1,   Beclin-1↑,1,   cardioP↑,1,   Catalase↑,1,   FASN↓,1,   GPx↑,1,   GSH↑,1,   GSTs↑,1,   iNOS↑,1,   lipid-P↓,1,   miR-29b↑,1,   NF-kB↑,1,   OS↑,1,   p62↓,1,   ROS↓,1,   SOD↑,1,   Sp1/3/4↓,3,   Sp1/3/4↑,1,   SREBP1↓,1,   VEGF↑,1,  
Total Targets: 21

Scientific Paper Hit Count for: Sp1/3/4, Specificity Protein
13 Resveratrol
1 Chemotherapy
1 Quercetin
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:141  Target#:506  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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