Resveratrol / Bcl-2 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


Bcl-2, B-cell CLL/lymphoma 2: Click to Expand ⟱
Source: HalifaxProj (inhibit) CGL-Driver Genes
Type: Antiapoptotic Oncogene
The proteins of BCL-2 family are classified into three subgroups, i.e., the anti-apoptotic/pro-survival proteins represented by BCL-2 and BCL-XL, the pro-apoptotic proteins represented by BAX and Bak, and the pro-apoptotic BH3-only proteins represented by BAD and BID.
Since the expression of Bcl-2 protein in tumor cells is much higher than that in normal cells, inhibitors targeting it have little effect on normal cells.
Scientific Papers found: Click to Expand⟱
685- EGCG,  CUR,  SFN,  RES,  GEN  The “Big Five” Phytochemicals Targeting Cancer Stem Cells: Curcumin, EGCG, Sulforaphane, Resveratrol and Genistein
- Analysis, NA, NA
Bcl-2↓, survivin↓, XIAP↓, EMT↓, Apoptosis↑, Nanog↓, cMyc↓, OCT4↓, Snail↓, Slug↓, Zeb1↓, TCF↓,
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↑,
4286- RES,    Neuroprotective Properties of Resveratrol and Its Derivatives—Influence on Potential Mechanisms Leading to the Development of Alzheimer’s Disease
- Review, AD, NA
*neuroP↑, *Inflam↓, *antiOx↑, *GSH↑, *HO-1↑, *iNOS↓, *BDNF↑, *p‑CREB↑, *PKA↑, *Bcl-2↑, *BAX↓, *IL1β↓, *IL6↓, *MMP9↓, *memory↑, *AMPK↑, *PGC-1α↓, *NF-kB↓, *Aβ↓, *SIRT1↑, *p‑tau↓, *PP2A↑, *lipid-P↓, *NLRP3↓, *BACE↓,
103- RES,  CUR,  QC,    The effect of resveratrol, curcumin and quercetin combination on immuno-suppression of tumor microenvironment for breast tumor-bearing mice
- vitro+vivo, BC, 4T1
ROS↑, MMP↓, Bcl-2↓, BAX↑, Casp9↑, T-Cell↑, TGF-β↓,
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↑,
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↓,
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↓,
2329- RES,    Resveratrol induces apoptosis in human melanoma cell through negatively regulating Erk/PKM2/Bcl-2 axis
- in-vitro, Melanoma, A375
P53↑, Bcl-2↓, BAX↑, Cyt‑c↑, ERK↓, PKM2↓, Apoptosis↑, γH2AX↑, Casp3↑, cl‑PARP1↑,
882- RES,    Resveratrol: A Double-Edged Sword in Health Benefits
- Review, NA, NA
AntiTum↑, Casp3↑, Casp9↑, BAX↑, Bcl-2↓, Bcl-xL↓, P53↑, NAF1↓, NRF2↑, ROS↑, Apoptosis↑, HDAC↓, TumCCA↑, TumAuto↑, angioG↓, iNOS↓,
3054- RES,    Resveratrol induced reactive oxygen species and endoplasmic reticulum stress-mediated apoptosis, and cell cycle arrest in the A375SM malignant melanoma cell line
- in-vitro, Melanoma, A375
TumCG↓, P21↑, p27↑, CycB/CCNB1↓, ROS↑, ER Stress↑, p‑p38↑, P53↑, p‑eIF2α↑, EP4↑, CHOP↑, Bcl-2↓, BAX↓, TumCCA↑, NRF2↓, ChemoSen↑, GSH↓,

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,   GSH↓, 1,   HO-1↑, 1,   lipid-P↑, 1,   NAF1↓, 1,   NRF2↓, 1,   NRF2↑, 2,   ROS↑, 4,   TAC?, 1,   xCT↓, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 1,   MMP↓, 2,   XIAP↓, 2,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 1,   GlutMet↓, 1,   PFK↓, 1,   PKM2↓, 1,   POLD1↓, 1,   SIRT1↑, 2,  

Cell Death ⓘ

AhR↓, 1,   Akt↓, 1,   p‑Akt↓, 1,   Apoptosis↑, 4,   BAX↓, 1,   BAX↑, 5,   Bcl-2↓, 9,   Bcl-xL↓, 2,   BIM↑, 1,   Casp3↑, 2,   Casp9↑, 2,   CK2↓, 1,   Cyt‑c↑, 2,   Diablo↑, 1,   DR4↑, 2,   DR5↑, 2,   FasL↓, 1,   Ferroptosis↑, 1,   iNOS↓, 1,   p27↑, 3,   p‑p38↑, 1,   survivin↓, 3,  

Transcription & Epigenetics ⓘ

tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   p‑eIF2α↑, 1,   ER Stress↑, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↓, 1,   p62↓, 1,   TumAuto↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   P53↑, 4,   cl‑PARP1↑, 1,   γH2AX↑, 2,  

Cell Cycle & Senescence ⓘ

CycB/CCNB1↓, 1,   cycD1/CCND1↓, 3,   P21↑, 1,   TumCCA↑, 3,  

Proliferation, Differentiation & Cell State ⓘ

CSCs↓, 1,   EMT↓, 2,   EP4↑, 1,   ERK↓, 1,   FOXO↑, 1,   FOXO4↓, 1,   Gli1↓, 1,   HDAC↓, 1,   IGF-1↓, 1,   mTOR↓, 1,   Nanog↓, 1,   NOTCH⇅, 1,   NOTCH2↓, 1,   OCT4↓, 1,   PI3K↓, 1,   p‑PI3K↓, 1,   PTCH1↓, 1,   Smo↓, 1,   STAT3↓, 1,   STAT5↓, 1,   TCF↓, 1,   TumCG↓, 1,   Wnt↓, 1,  

Migration ⓘ

E-cadherin↑, 2,   Fibronectin↓, 1,   HLA↑, 1,   Ki-67↓, 1,   MALAT1↓, 1,   MMP2↓, 1,   MMP9↓, 1,   Slug↓, 2,   SMAD2↓, 1,   p‑SMAD2↓, 1,   SMAD3↓, 1,   p‑SMAD3↓, 1,   Snail↓, 2,   TGF-β↓, 2,   TumCI↓, 1,   TumCP↓, 1,   TumMeta↓, 1,   Vim?, 1,   Zeb1↓, 2,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   Hif1a↓, 1,   VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   CRP↓, 1,   FOXP3↓, 1,   IL1β↓, 1,   JAK↓, 1,   NF-kB↓, 1,   p‑NF-kB↓, 1,   PD-1↓, 1,   T-Cell↑, 1,   Th1 response↑, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 2,   eff↑, 1,   RadioS↑, 2,  

Clinical Biomarkers ⓘ

CRP↓, 1,   Ki-67↓, 1,  

Functional Outcomes ⓘ

AntiTum↑, 1,   NKG2D↑, 1,  

Infection & Microbiome ⓘ

CD8+↑, 1,  
Total Targets: 122

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   GSH↑, 2,   HO-1↑, 2,   Keap1↓, 1,   lipid-P↓, 1,   NQO1↑, 1,   NRF2↑, 1,   ROS↓, 1,  

Mitochondria & Bioenergetics ⓘ

PGC-1α↓, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   p‑CREB↑, 1,   SIRT1↑, 1,  

Cell Death ⓘ

BAX↓, 1,   Bcl-2↑, 1,   iNOS↓, 1,  

Migration ⓘ

MMP9↓, 1,   PKA↑, 1,  

Immune & Inflammatory Signaling ⓘ

IL1β↓, 1,   IL6↓, 1,   Inflam↓, 2,   NF-kB↓, 1,  

Synaptic & Neurotransmission ⓘ

BDNF↑, 1,   p‑tau↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 1,   BACE↓, 1,   NLRP3↓, 1,   PP2A↑, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 2,  

Clinical Biomarkers ⓘ

IL6↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 1,   memory↑, 1,   neuroP↑, 2,  
Total Targets: 33

Scientific Paper Hit Count for: Bcl-2, B-cell CLL/lymphoma 2
10 Resveratrol
2 Curcumin
1 EGCG (Epigallocatechin Gallate)
1 Sulforaphane (mainly Broccoli)
1 Genistein (soy isoflavone)
1 Quercetin
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#:27  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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