Resveratrol / cycD1/CCND1 Cancer Research Results

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

Rank Pathway / Axis Cancer Cells Normal Cells Label Primary Interpretation Notes
1 Reactive oxygen species (ROS) ↑ ROS (dose- & context-dependent) ↓ ROS / buffered Conditional Driver Biphasic redox modulation Resveratrol can act as a pro-oxidant in cancer cells while functioning as an antioxidant in normal cells
2 Mitochondrial integrity / intrinsic apoptosis ↓ ΔΨm; ↑ caspase activation ↔ preserved Driver Execution of intrinsic apoptosis Mitochondrial dysfunction and apoptosis follow ROS elevation in cancer cells
3 SIRT1 / AMPK axis ↑ AMPK; context-dependent SIRT1 modulation ↑ SIRT1 / ↑ AMPK Driver Metabolic stress signaling Resveratrol modulates energy-sensing pathways affecting survival and metabolism
4 PI3K → AKT → mTOR axis ↓ AKT / ↓ mTOR ↔ adaptive suppression Secondary Growth and anabolic inhibition Downregulation of growth signaling contributes to cytostasis and apoptosis sensitization
5 NF-κB signaling ↓ NF-κB activation ↓ inflammatory NF-κB tone Secondary Suppression of survival and inflammatory transcription NF-κB inhibition contributes to reduced proliferation and invasion
6 Cell cycle regulation ↑ G1/S or G2/M arrest ↔ largely spared Phenotypic Cytostatic growth control Cell-cycle arrest reflects upstream signaling disruption
7 HIF-1α / VEGF axis ↓ HIF-1α; ↓ VEGF ↔ minimal Secondary Anti-angiogenic pressure Interference with hypoxia-driven adaptation and angiogenesis


cycD1/CCND1, cyclin D1 pathway: Click to Expand ⟱
Source:
Type:
Also called CCND1 Gatekeeper of Cell-Cycle Commitment
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↓, *antiOx↑, *AntiAg↑, *chemoPv↑, ChemoSen↑, BioAv↑, Half-Life↝, COX2↓, cycD1/CCND1↓, CDK2↓, CDK4↓, CDK6↓, P21↑, MMP9↓, NF-kB↓, Telomerase↓, PSA↓, MAPK↑, P53↑,
3061- RES,    The Anticancer Effects of Resveratrol: Modulation of Transcription Factors
- Review, Var, NA
AhR↓, NRF2↑, *NQO1↑, *HO-1↑, *GSH↑, P53↑, Cyt‑c↑, Diablo↑, Bcl-2↓, Bcl-xL↓, survivin↓, XIAP↓, FOXO↑, p‑PI3K↓, p‑Akt↓, BIM↑, DR4↑, DR5↑, p27↑, cycD1/CCND1↓, SIRT1↑, NF-kB↓, ATF3↑,
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/CCND1↓, COX2↓, cMyc↓,
3098- RES,    Regulation of Cell Signaling Pathways and miRNAs by Resveratrol in Different Cancers
- Review, Var, NA
NOTCH2↓, Wnt↓, β-catenin/ZEB1↓, p‑SMAD2↓, p‑SMAD3↓, PTCH1↓, Smo↓, Gli1↓, E-cadherin↑, NOTCH⇅, TAC?, NKG2D↑, DR4↑, survivin↓, DR5↑, BAX↑, p27↑, cycD1/CCND1↓, Bcl-2↓, STAT3↓, STAT5↓, JAK↓, DNAdam↑, 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↓, TumCMig↓, TumCI↓, cycD1/CCND1↓, cMyc↓, MMP2↓, MMP9↓, SOX2↓, Akt↓, STAT3↓, α-SMA↓,
1489- RES,    Molecular mechanisms of resveratrol as chemo and radiosensitizer in cancer
- Review, Var, NA
RadioS↑, ChemoSen↑, *BioAv↓, *BioAv↑, Ferroptosis↑, lipid-P↑, xCT↓, GPx4↓, *BioAv↑, COX2↓, cycD1/CCND1↓, FasL↓, FOXP3↓, HLA↑, p‑NF-kB↓, BAX↑, Bcl-2↓, MALAT1↓,
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↑, PDH↑, Ca+2↝, TumCP↓, lactateProd↓, OCR↑, ECAR↓, *ECAR∅, *other?, cycE/CCNE↑, cycA1/CCNA1↑, TumCCA↑, cycD1/CCND1↑, 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↑, cycD1/CCND1↓, Bcl-xL↓, Mcl-1↓, other↓,
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↑, p27↑, cycD1/CCND1↓, TumCP↓, IGF-1R↓, Akt↓, Wnt↓, P53↑, Apoptosis↑, Sp1/3/4↓, cl‑PARP↑, β-catenin/ZEB1↓, MDM2↓,
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↓, Apoptosis↑, Sp1/3/4↓, p27↓, P21↓, cycD1/CCND1↓, Mcl-1↓, survivin↓,

Showing Research Papers: 1 to 10 of 10

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 10

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

ATF3↑, 1,   Ferroptosis↑, 1,   GPx4↓, 1,   lipid-P↑, 1,   NRF2↑, 1,   OXPHOS↑, 1,   TAC?, 1,   xCT↓, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↑, 1,   OCR↑, 1,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 2,   ECAR↓, 1,   Glycolysis↓, 1,   lactateProd↓, 1,   PDH↑, 1,   PPP↓, 1,   SIRT1↑, 1,  

Cell Death ⓘ

AhR↓, 1,   Akt↓, 2,   p‑Akt↓, 1,   Apoptosis↑, 2,   BAX↑, 2,   Bcl-2↓, 3,   Bcl-xL↓, 2,   BIM↑, 1,   Cyt‑c↑, 1,   Diablo↑, 1,   DR4↑, 2,   DR5↑, 2,   FasL↓, 1,   Ferroptosis↑, 1,   MAPK↑, 1,   Mcl-1↓, 2,   MDM2↓, 1,   p27↓, 1,   p27↑, 3,   survivin↓, 4,   Telomerase↓, 1,  

Kinase & Signal Transduction ⓘ

Sp1/3/4↓, 2,  

Transcription & Epigenetics ⓘ

other↓, 1,   tumCV↓, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   P53↑, 3,   cl‑PARP↑, 1,   γH2AX↑, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 1,   CDK4↓, 1,   cycA1/CCNA1↑, 1,   cycD1/CCND1↓, 9,   cycD1/CCND1↑, 1,   cycE/CCNE↑, 1,   P21↓, 1,   P21↑, 1,   TumCCA↑, 3,  

Proliferation, Differentiation & Cell State ⓘ

ALDH1A1↓, 1,   CD133↓, 1,   CD44↓, 1,   CSCs↓, 1,   FOXO↑, 1,   Gli1↓, 1,   IGF-1R↓, 1,   Nanog↓, 1,   NOTCH⇅, 1,   NOTCH2↓, 1,   OCT4↓, 1,   p‑PI3K↓, 1,   PTCH1↓, 1,   Shh↓, 1,   Smo↓, 1,   SOX2↓, 1,   STAT3↓, 3,   STAT5↓, 1,   TumCG↓, 1,   Wnt↓, 2,  

Migration ⓘ

Ca+2↝, 1,   E-cadherin↑, 1,   HLA↑, 1,   MALAT1↓, 1,   MMP2↓, 2,   MMP9↓, 3,   Smad1↓, 1,   p‑SMAD2↓, 1,   p‑SMAD3↓, 1,   Snail↓, 1,   TumCI↓, 1,   TumCMig↓, 1,   TumCP↓, 3,   Twist↓, 1,   α-SMA↓, 1,   β-catenin/ZEB1↓, 2,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 3,   FOXP3↓, 1,   JAK↓, 1,   NF-kB↓, 2,   p‑NF-kB↓, 1,   PSA↓, 1,  

Hormonal & Nuclear Receptors ⓘ

CDK6↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 1,   ChemoSen↑, 2,   Half-Life↝, 1,   RadioS↑, 1,  

Clinical Biomarkers ⓘ

PSA↓, 1,  

Functional Outcomes ⓘ

NKG2D↑, 1,  
Total Targets: 104

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   GSH↑, 1,   HO-1↑, 1,   NQO1↑, 1,  

Core Metabolism/Glycolysis ⓘ

ECAR∅, 1,  

Transcription & Epigenetics ⓘ

other?, 1,  

Migration ⓘ

AntiAg↑, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 2,  

Functional Outcomes ⓘ

chemoPv↑, 1,  
Total Targets: 11

Scientific Paper Hit Count for: cycD1/CCND1, cyclin D1 pathway
10 Resveratrol
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:141  Target#:73  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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