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


cycD1, cyclin D1 pathway: Click to Expand ⟱
Source:
Type:
Also called CCND1
The main function of cyclin D1 is to maintain cell cycle and to promote cell proliferation. Cyclin D1 is a key regulatory protein involved in the cell cycle, particularly in the transition from the G1 phase to the S phase. It is part of the cyclin-dependent kinase (CDK) complex, where it binds to CDK4 or CDK6 to promote cell cycle progression.
Cyclin D1 is crucial for the regulation of the cell cycle. Overexpression or dysregulation of cyclin D1 can lead to uncontrolled cell proliferation, a hallmark of cancer.
Cyclin D1 is often found to be overexpressed in various cancers.
Cyclin D1 can interact with tumor suppressor proteins, such as retinoblastoma (Rb). When cyclin D1 is overexpressed, it can lead to the phosphorylation and inactivation of Rb, releasing E2F transcription factors that promote the expression of genes required for DNA synthesis and cell cycle progression.
Cyclin D1 is influenced by various signaling pathways, including the PI3K/Akt and MAPK pathways, which are often activated in cancer.
In some cancers, high levels of cyclin D1 expression have been associated with poor prognosis, making it a potential biomarker for cancer progression and treatment response.
Scientific Papers found: Click to Expand⟱
3063- RES,    Resveratrol: A Review of Pre-clinical Studies for Human Cancer Prevention
- Review, Var, NA
*Inflam↓, Resveratrol is known to have potent anti-inflammatory and anti-oxidant effects and to inhibit platelet aggregation and the growth of a variety of cancer cells.
*antiOx↑,
*AntiAg↑,
*chemoP↑, Its potential chemopreventive and chemotherapeutic activities have been demonstrated in all three stages of carcinogenesis
ChemoSen↑,
BioAv↑, Compared to other known polyphenols, such as quercetin and catechin, trans-resveratrol is well absorbed much more efficiently following oral administration to humans
Half-Life↝, Compared to resveratrol, which has a plasma half-life of 8–14 min, the metabolites have a plasma half-life of about 9.2 hours
COX2↓, there was inhibited expression of anti-apoptotic proteins, such as survivin, and markers of tumor promotion, cyclooxygenase (COX)-2, and ornithine decarboxylase (ODC) were observed
cycD1↓, Resveratrol decreased the expression of cyclins D1 and D2, Cdk 2, 4 and 6, and proliferating cell nuclear antigen (PCNA) whereas p21WAF1/CIP1 was increased
CDK2↓,
CDK4↓,
CDK6↓,
P21↑,
MMP9↓, associated with decreased COX-2 and matrix metalloprotease-9 expression and suppression of NFκB activation
NF-kB↓,
Telomerase↓, Relatively high concentrations also substantially downregulate telomerase activity
PSA↓, Resveratrol downregulates PSA by a mechanism independent of changes in AR
MAPK↑, Resveratrol treatment of various prostate cells also accompanied the activation of MAPK signaling and an increase in cellular p53
P53↑,

3061- RES,    The Anticancer Effects of Resveratrol: Modulation of Transcription Factors
- Review, Var, NA
AhR↓, Several reports demonstrate the inhibitory effects of resveratrol on AhR-mediated activation of phase I enzymes.
NRF2↑, Bishayee et al. (18) demonstrated that attenuation of DENA (diethyl nitrosamine)-induced liver carcinogenesis by resveratrol was mediated by increased Nrf2 expression.
*NQO1↑, Induction of Nrf2 signaling by resveratrol resulted in increased expression of NQO1, heme-oxygenase 1 (HO-1), and glutamate cysteine ligase catalytic subunit in cigarette smoke extract-treated bronchial epithelial cells
*HO-1↑,
*GSH↑, observed restored glutathione levels in cigarette smoke extract-treated A549 lung alveolar epithelial cancer cells by resveratrol;
P53↑, we highlight reported resveratrol-induced, p53-mediated anticancer mechanisms.
Cyt‑c↑, release of mitochondria proteins (e.g. cytochrome c, Smac/DIABLO, etc.) to the cytosol, thus triggering suppression of inhibitors of apoptosis proteins (e.g. Bcl2, Bcl-XL, survivin, XIAP, etc.) and caspase activation in several cancers
Diablo↑,
Bcl-2↓,
Bcl-xL↓,
survivin↓,
XIAP↓,
FOXO↑, activation of FoxO transcription factors is implicated in the observed anticancer activities of resveratrol.
p‑PI3K↓, resveratrol's ability to inhibit the phosphorylation of PI3K/Akt (
p‑Akt↓,
BIM↑, Bim/TRAIL/DR4/DR5/p27KIP1 induction and cyclin D1 inhibition) of resveratrol on prostate cancer cells
DR4↑,
DR5↑,
p27↑,
cycD1↓,
SIRT1↑, resveratrol is considered a SIRT1 agonist
NF-kB↓, resveratrol not only curbs expression of NF-κB, but also impedes the phosphorylation of IκBα thereby keeping the constitutive NF-κB subunit in an inactive state, resulting in suppression of the inflammatory
ATF3↑, Furthermore, increased ATF3 expression by resveratrol facilitated induction of apoptosis

3098- RES,    Regulation of Cell Signaling Pathways and miRNAs by Resveratrol in Different Cancers
- Review, Var, NA
NOTCH2↓, resveratrol has been reported to target multiple proteins in ovarian cancer, markedly reducing NOTCH2 and HES1 in OVCAR-3 and CAOV-3 cells
Wnt↓, In CAOV-3 cells, resveratrol downregulated WNT2 and reduced the nuclear accumulation of β-catenin
β-catenin/ZEB1↓,
p‑SMAD2↓, Resveratrol effectively inhibits SMAD proteins
p‑SMAD3↓, Resveratrol has been reported to reduce phosphorylated-SMAD2/3 in colorectal cancer LoVo cells
PTCH1↓, PTCH, SMO, and GLI-1 were also inhibited in resveratrol-treated colorectal cancer HCT116 cells
Smo↓,
Gli1↓,
E-cadherin↑, resveratrol upregulated E-cadherin
NOTCH⇅, Although some reports document efficient inhibition of different proteins of the NOTCH pathway by resveratrol to inhibit cancer, there are conflicting reports that resveratrol can activate the NOTCH pathway, leading to its anticancer activity.
TAC?,
NKG2D↑, Resveratrol has been found to increase the cell-surface expression of NKG2D ligands and DR4 along
DR4↑,
survivin↓, Resveratrol dose-dependently downregulated survivin in HepG2 cells.
DR5↑, resveratrol upregulated DR4, DR5, Bax, and p27(/KIP1) and inhibited the expression of cyclin D1 and Bcl-2
BAX↑,
p27↑,
cycD1↓,
Bcl-2↓,
STAT3↓, Resveratrol exerts inhibitory effects on the constitutive activation of STAT3 and STAT5.
STAT5↓,
JAK↓, Resveratrol has also been shown to prevent the activation of JAK,
DNAdam↑, Resveratrol induced DNA damage, as evidenced by the presence of multiple γ-H2AX foci after treatment with 25 μM resveratrol.
γH2AX↑,

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↓, 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)

1489- RES,    Molecular mechanisms of resveratrol as chemo and radiosensitizer in cancer
- Review, Var, NA
RadioS↑,
ChemoSen↑,
*BioAv↓, However, in vivo experimental models have demonstrated that RSV is rapidly metabolized and eliminated, which leads to low bioavailability of the compound. 75% of RSV has been shown to be absorbed orally, only 1% is detected in the blood plasma
*BioAv↑, nanocarrier of RSV-loaded poly (ε-caprolactone)-poly (ethylene glycol) nanoparticles with an erythrocyte membrane. This system improved RSV’s poor water solubility
Ferroptosis↑, SV could induce ferroptotic cell death in colorectal cancer by initiating lipid peroxidation and suppressing the expression of SLC7A11 and GPX4
lipid-P↑,
xCT↓,
GPx4↓,
*BioAv↑, Bioactive or bioenhancer compounds have also been used (piperine, quercetin, biflavone ginkgetin) that, in combination with RSV, improve bioavailability, solubility, absorption, and cellular permeability
COX2↓, inhibiting Cyclooxygenase-COX
cycD1↓,
FasL↓,
FOXP3↓,
HLA↑,
p‑NF-kB↓, decrease NF-ĸB phosphorylation
BAX↑,
Bcl-2↓,
MALAT1↓, decrease the expression of the lncRNA MALAT1 in colorectal and gastric cancer cells through the Wnt/β-catenin signaling pathway

993- RES,    Resveratrol reverses the Warburg effect by targeting the pyruvate dehydrogenase complex in colon cancer cells
- in-vitro, CRC, Caco-2 - in-vivo, Nor, HCEC 1CT
TumCG↓,
Glycolysis↓,
PPP↓,
ATP↑, significant increase (20%) in ATP production
PDH↑, Resveratrol targets the pyruvate dehydrogenase (PDH) complex, a key mitochondrial gatekeeper of energy metabolism, leading to an enhanced PDH activity.
Ca+2↝, resveratrol is a potent modulator of many cellular Ca2+ signaling pathways. Ca2+ is a key mediator of the effect of resveratrol on the oxidative capacity of colon cancer cells.
TumCP↓,
lactateProd↓,
OCR↑, increase of oxygen consumption rate (OCR) both in normal colonic epithelial HCEC 1CT cells
ECAR↓, Following treatment with resveratrol (10 µM, 48 hr), the ECAR was unchanged in normal HCEC 1CT cells, whereas it was significantly reduced (31%) in HCEC 1CT RPA cells ****
*ECAR∅, Following treatment with resveratrol (10 µM, 48 hr), the ECAR was unchanged in normal HCEC 1CT cells
*other?, Resveratrol promotes a shift from respiration to glycolysis in cancer-like cells, but not in normal colonocytes
cycE↑, Resveratrol inhibited cell cycle progression by enhancing the levels of cyclin E and cyclin A
cycA1↑,
TumCCA↑,
cycD1↑, and by decreasing cyclin D1
OXPHOS↑, Taken together, these observations indicate that exposure to resveratrol leads to a metabolic reorientation from aerobic glycolysis toward OXPHOS.

881- RES,    Resveratrol inhibits Src and Stat3 signaling and induces the apoptosis of malignant cells containing activated Stat3 protein
- in-vitro, BC, MDA-MB-231 - in-vitro, PC, PANC1 - in-vitro, Pca, DU145
TumCCA↑, at the G0 -G1 phase or at the S phase (malignant cells contain activated Stat3)
cycD1↓,
Bcl-xL↓,
Mcl-1↓,
other↓, not effective on cells lacking aberrant Stat3 activity

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: 9

Results for Effect on Cancer/Diseased Cells:
AhR↓,1,   Akt↓,2,   p‑Akt↓,1,   Apoptosis↑,2,   ATF3↑,1,   ATP↑,1,   BAX↑,2,   Bcl-2↓,3,   Bcl-xL↓,2,   BIM↑,1,   BioAv↑,1,   Ca+2↝,1,   CDK2↓,1,   CDK4↓,1,   CDK6↓,1,   ChemoSen↑,2,   cMyc↓,1,   COX2↓,2,   cycA1↑,1,   cycD1↓,8,   cycD1↑,1,   cycE↑,1,   Cyt‑c↑,1,   Diablo↑,1,   DNAdam↑,1,   DR4↑,2,   DR5↑,2,   E-cadherin↑,1,   ECAR↓,1,   FasL↓,1,   Ferroptosis↑,1,   FOXO↑,1,   FOXP3↓,1,   Gli1↓,1,   Glycolysis↓,1,   GPx4↓,1,   Half-Life↝,1,   HLA↑,1,   IGF-1R↓,1,   JAK↓,1,   lactateProd↓,1,   lipid-P↑,1,   MALAT1↓,1,   MAPK↑,1,   Mcl-1↓,2,   MDM2↓,1,   MMP2↓,1,   MMP9↓,2,   NF-kB↓,2,   p‑NF-kB↓,1,   NKG2D↑,1,   NOTCH⇅,1,   NOTCH2↓,1,   NRF2↑,1,   OCR↑,1,   other↓,1,   OXPHOS↑,1,   P21↓,1,   P21↑,1,   p27↓,1,   p27↑,3,   P53↑,3,   cl‑PARP↑,1,   PDH↑,1,   p‑PI3K↓,1,   PPP↓,1,   PSA↓,1,   PTCH1↓,1,   RadioS↑,1,   SIRT1↑,1,   p‑SMAD2↓,1,   p‑SMAD3↓,1,   Smo↓,1,   SOX2↓,1,   Sp1/3/4↓,2,   STAT3↓,2,   STAT5↓,1,   survivin↓,3,   TAC?,1,   Telomerase↓,1,   TumCCA↑,3,   TumCG↓,1,   TumCI↓,1,   TumCMig↓,1,   TumCP↓,3,   tumCV↓,1,   Wnt↓,2,   xCT↓,1,   XIAP↓,1,   α-SMA↓,1,   β-catenin/ZEB1↓,2,   γH2AX↑,1,  
Total Targets: 92

Results for Effect on Normal Cells:
AntiAg↑,1,   antiOx↑,1,   BioAv↓,1,   BioAv↑,2,   chemoP↑,1,   ECAR∅,1,   GSH↑,1,   HO-1↑,1,   Inflam↓,1,   NQO1↑,1,   other?,1,  
Total Targets: 11

Scientific Paper Hit Count for: cycD1, cyclin D1 pathway
9 Resveratrol
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:141  Target#:73  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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