Resveratrol / ROS 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↓">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


ROS, Reactive Oxygen Species: Click to Expand ⟱
Source: HalifaxProj (inhibit)
Type:
Reactive oxygen species (ROS) are highly reactive molecules that contain oxygen and can lead to oxidative stress in cells. They play a dual role in cancer biology, acting as both promoters and suppressors of cancer.
ROS can cause oxidative damage to DNA, leading to mutations that may contribute to cancer initiation and progression. So normally you want to inhibit ROS to prevent cell mutations.
However excessive ROS can induce apoptosis (programmed cell death) in cancer cells, potentially limiting tumor growth. Chemotherapy typically raises ROS.
-mitochondria is the main source of reactive oxygen species (ROS) (and the ETC is heavily related)

"Reactive oxygen species (ROS) are two electron reduction products of oxygen, including superoxide anion, hydrogen peroxide, hydroxyl radical, lipid peroxides, protein peroxides and peroxides formed in nucleic acids 1. They are maintained in a dynamic balance by a series of reduction-oxidation (redox) reactions in biological systems and act as signaling molecules to drive cellular regulatory pathways."
"During different stages of cancer formation, abnormal ROS levels play paradoxical roles in cell growth and death 8. A physiological concentration of ROS that maintained in equilibrium is necessary for normal cell survival. Ectopic ROS accumulation promotes cell proliferation and consequently induces malignant transformation of normal cells by initiating pathological conversion of physiological signaling networks. Excessive ROS levels lead to cell death by damaging cellular components, including proteins, lipid bilayers, and chromosomes. Therefore, both scavenging abnormally elevated ROS to prevent early neoplasia and facilitating ROS production to specifically kill cancer cells are promising anticancer therapeutic strategies, in spite of their contradictoriness and complexity."
"ROS are the collection of derivatives of molecular oxygen that occur in biology, which can be categorized into two types, free radicals and non-radical species. The non-radical species are hydrogen peroxide (H 2O 2 ), organic hydroperoxides (ROOH), singlet molecular oxygen ( 1 O 2 ), electronically excited carbonyl, ozone (O3 ), hypochlorous acid (HOCl, and hypobromous acid HOBr). Free radical species are super-oxide anion radical (O 2•−), hydroxyl radical (•OH), peroxyl radical (ROO•) and alkoxyl radical (RO•) [130]. Any imbalance of ROS can lead to adverse effects. H2 O 2 and O 2 •− are the main redox signalling agents. The cellular concentration of H2 O 2 is about 10−8 M, which is almost a thousand times more than that of O2 •−".
"Radicals are molecules with an odd number of electrons in the outer shell [393,394]. A pair of radicals can be formed by breaking a chemical bond or electron transfer between two molecules."

Recent investigations have documented that polyphenols with good antioxidant activity may exhibit pro-oxidant activity in the presence of copper ions, which can induce apoptosis in various cancer cell lines but not in normal cells. "We have shown that such cell growth inhibition by polyphenols in cancer cells is reversed by copper-specific sequestering agent neocuproine to a significant extent whereas iron and zinc chelators are relatively ineffective, thus confirming the role of endogenous copper in the cytotoxic action of polyphenols against cancer cells. Therefore, this mechanism of mobilization of endogenous copper." > Ions could be one of the important mechanisms for the cytotoxic action of plant polyphenols against cancer cells and is possibly a common mechanism for all plant polyphenols. In fact, similar results obtained with four different polyphenolic compounds in this study, namely apigenin, luteolin, EGCG, and resveratrol, strengthen this idea.
Interestingly, the normal breast epithelial MCF10A cells have earlier been shown to possess no detectable copper as opposed to breast cancer cells [24], which may explain their resistance to polyphenols apigenin- and luteolin-induced growth inhibition as observed here (Fig. 1). We have earlier proposed [25] that this preferential cytotoxicity of plant polyphenols toward cancer cells is explained by the observation made several years earlier, which showed that copper levels in cancer cells are significantly elevated in various malignancies. Thus, because of higher intracellular copper levels in cancer cells, it may be predicted that the cytotoxic concentrations of polyphenols required would be lower in these cells as compared to normal cells."

Majority of ROS are produced as a by-product of oxidative phosphorylation, high levels of ROS are detected in almost all cancers.
-It is well established that during ER stress, cytosolic calcium released from the ER is taken up by the mitochondrion to stimulate ROS overgeneration and the release of cytochrome c, both of which lead to apoptosis.

Note: Products that may raise ROS can be found using this database, by:
Filtering on the target of ROS, and selecting the Effect Direction of ↑

Targets to raise ROS (to kill cancer cells):
• NADPH oxidases (NOX): NOX enzymes are involved in the production of ROS.
    -Targeting NOX enzymes can increase ROS levels and induce cancer cell death.
    -eNOX2 inhibition leads to a high NADH/NAD⁺ ratio which can lead to increased ROS
• Mitochondrial complex I: Inhibiting can increase ROS production
• P53: Activating p53 can increase ROS levels(by inducing the expression of pro-oxidant genes)
• Nrf2 inhibition: regulates the expression of antioxidant genes. Inhibiting Nrf2 can increase ROS levels
• Glutathione (GSH): an antioxidant. Depleting GSH can increase ROS levels
• Catalase: Catalase converts H2O2 into H2O+O. Inhibiting catalase can increase ROS levels
• SOD1: converts superoxide into hydrogen peroxide. Inhibiting SOD1 can increase ROS levels
• PI3K/AKT pathway: regulates cell survival and metabolism. Inhibiting can increase ROS levels
• HIF-1α inhibition: regulates genes involved in metabolism and angiogenesis. Inhibiting HIF-1α can increase ROS
• Glycolysis: Inhibiting glycolysis can increase ROS levels • Fatty acid oxidation: Cancer cells often rely on fatty acid oxidation for energy production.
-Inhibiting fatty acid oxidation can increase ROS levels
• ER stress: Endoplasmic reticulum (ER) stress can increase ROS levels
• Autophagy: process by which cells recycle damaged organelles and proteins.
-Inhibiting autophagy can increase ROS levels and induce cancer cell death.
• KEAP1/Nrf2 pathway: regulates the expression of antioxidant genes.
    -Inhibiting KEAP1 or activating Nrf2 can increase ROS levels and induce cancer cell death.
• DJ-1: regulates the expression of antioxidant genes. Inhibiting DJ-1 can increase ROS levels
• PARK2: regulates the expression of antioxidant genes. Inhibiting PARK2 can increase ROS levels
• SIRT1 inhibition:regulates the expression of antioxidant genes. Inhibiting SIRT1 can increase ROS levels
• AMPK activation: regulates energy metabolism and can increase ROS levels when activated.
• mTOR inhibition: regulates cell growth and metabolism. Inhibiting mTOR can increase ROS levels
• HSP90 inhibition: regulates protein folding and can increase ROS levels when inhibited.
• Proteasome: degrades damaged proteins. Inhibiting the proteasome can increase ROS levels
• Lipid peroxidation: a process by which lipids are oxidized, leading to the production of ROS.
    -Increasing lipid peroxidation can increase ROS levels
• Ferroptosis: form of cell death that is regulated by iron and lipid peroxidation.
    -Increasing ferroptosis can increase ROS levels
• Mitochondrial permeability transition pore (mPTP): regulates mitochondrial permeability.
    -Opening the mPTP can increase ROS levels
• BCL-2 family proteins: regulate apoptosis and can increase ROS levels when inhibited.
• Caspase-independent cell death: a form of cell death that is regulated by ROS.
    -Increasing caspase-independent cell death can increase ROS levels
• DNA damage response: regulates the repair of DNA damage. Increasing DNA damage can increase ROS
• Epigenetic regulation: process by which gene expression is regulated.
    -Increasing epigenetic regulation can increase ROS levels

-PKM2, but not PKM1, can be inhibited by direct oxidation of cysteine 358 as an adaptive response to increased intracellular reactive oxygen species (ROS)

ProOxidant Strategy:(inhibit the Mevalonate Pathway (likely will also inhibit GPx)
-HydroxyCitrate (HCA) found as supplement online and typically used in a dose of about 1.5g/day or more
-Atorvastatin typically 40-80mg/day, -Dipyridamole typically 200mg 2x/day Combined effect research
-Lycopene typically 100mg/day range (note debatable as it mainly lowers NRF2)

Dual Role of Reactive Oxygen Species and their Application in Cancer Therapy 
ROS-Inducing Interventions in Cancer — Canonical + Mechanistic Reference
-generated from AI and Cancer database
ROS rating:  +++ strong | ++ moderate | + weak | ± mixed | 0 none
NRF2:        ↓ suppressed | ↑ activated | ± mixed | 0 none
Conditions:  [D] dose  [Fe] metal  [M] metabolic  [O₂] oxygen
             [L] light [F] formulation [T] tumor-type [C] combination




Item ROS↑ NRF2 Condition Mechanism Class Remarks 



ROS">Piperlongumine
+++ ↓ [D][T] ROS-dominant






ROS">Shikonin
+++↓/±[D][T]ROS-dominant






ROS">Vitamin K3 (menadione)
+++↓[D]ROS-dominant






ROS">Copper (ionic / nano)
+++↓[Fe][F]ROS-dominant






ROS">Sodium Selenite
+++↓[D]ROS-dominant






ROS">Juglone
+++↓[D]ROS-dominant






ROS">Auranofin
+++↓[D]ROS-dominant






ROS">Photodynamic Therapy (PDT)
+++0[L][O₂]ROS-dominant






ROS">Radiotherapy / Radiation
+++0[O₂]ROS-dominant






ROS">Doxorubicin
+++↓[D]ROS-dominant






ROS">Cisplatin
++↓[D][T]ROS-dominant






ROS">Salinomycin
++↓[D][T]ROS-dominant






ROS">Artemisinin / DHA
++↓[Fe][T]ROS-dominant






ROS">Sulfasalazine
++↓[C][T]ROS-dominant






ROS">FMD / fasting
++↓[M][C][O₂]ROS-dominant






ROS">Vitamin C (pharmacologic)
++↓[Fe][D]ROS-dominant






ROS">Silver nanoparticles
++±[F][D]ROS-dominant






ROS">Gambogic acid
++↓[D][T]ROS-dominant






ROS">Parthenolide
++↓[D][T]ROS-dominant






ROS">Plumbagin
++↓[D]ROS-dominant






ROS">Allicin
++↓[D]ROS-dominant






ROS">Ashwagandha (Withaferin A)
++↓[D][T]ROS-dominant






ROS">Berberine
++↓[D][M]ROS-dominant






ROS">PEITC
++↓[D][C]ROS-dominant






ROS">Methionine restriction
+↓[M][C][T]ROS-secondary






ROS">DCA
+±[M][T]ROS-secondary






ROS">Capsaicin
+±[D][T]ROS-secondary






ROS">Galloflavin
+0[D]ROS-secondary






ROS">Piperine
+±[D][F]ROS-secondary






ROS">Propyl gallate
+↓[D]ROS-secondary






ROS">Scoulerine
+?[D][T]ROS-secondary






ROS">Thymoquinone
±±[D][T]Dual redox






ROS">Emodin
±±[D][T]Dual redox






ROS">Alpha-lipoic acid (ALA)
±↑[D][M]NRF2-dominant






ROS">Curcumin
±↑/↓[D][F]NRF2-dominant






ROS">EGCG
±↑/↓[D][O₂]NRF2-dominant






ROS">Quercetin
±↑/↓[D][Fe]NRF2-dominant






ROS">Resveratrol
±↑[D][M]NRF2-dominant






ROS">Sulforaphane
±↑↑[D]NRF2-dominant






ROS">Lycopene
0↑—Antioxidant






ROS">Rosmarinic acid
0↑—Antioxidant






ROS">Citrate
00—Neutral


Scientific Papers found: Click to Expand⟱
2206- AgNPs,  RES,    ENHANCED EFFICACY OF RESVERATROL-LOADED SILVER NANOPARTICLE IN ATTENUATING SEPSIS-INDUCED ACUTE LIVER INJURY: MODULATION OF INFLAMMATION, OXIDATIVE STRESS, AND SIRT1 ACTIVATION
- in-vivo, Nor, NA
*hepatoP↑, *Inflam↓, *NF-kB↓, *VEGF↓, *SIRT1↑, *ROS↓, *Dose↝, *Catalase↑, *MDA↓, *MPO↓, *NO↓, *ALAT↓, *AST↓, *antiOx↑,
6027- CGA,  CUR,  EGCG,  QC,  RES  Contribution of Non-Coding RNAs to Anticancer Effects of Dietary Polyphenols: Chlorogenic Acid, Curcumin, Epigallocatechin-3-Gallate, Genistein, Quercetin and Resveratrol
- Review, Nor, NA
*ROS↓, ROS↑,
5780- CRMs,  HCAs,  RES,  Sper,  ASA  Caloric Restriction Mimetics against Age-Associated Disease: Targets, Mechanisms, and Therapeutic Potential
- Review, Var, NA
*OS↑, *AntiAge↑, *cardioP↑, *neuroP↑, AntiCan↑, *TNF-α↓, *Weight↓, *BP↓, *Inflam↓, *Insulin↓, *ROS↓, *AMPK↑, *mTOR↓, *SIRT1↑, CRM↑,
3748- CUR,  RES,  Hup,  Riv,  Gala  Natural acetylcholinesterase inhibitors: A multi-targeted therapeutic potential in Alzheimer's disease
- Review, AD, NA
*AChE↓, *Inflam↓, *Aβ↓, *cognitive↑, *ROS↓,
872- CUR,  RES,    New Insights into Curcumin- and Resveratrol-Mediated Anti-Cancer Effects
- in-vitro, BC, TUBO - in-vitro, BC, SALTO
TumCP↓, tumCV↓, p62↓, p62↑, TumAuto↑, TumAuto↓, ROS↑, ROS↓, CHOP↑,
4703- PTS,  RES,    Pterostilbene and resveratrol: Exploring their protective mechanisms against skin photoaging - A scoping review
- NA, Nor, NA
*AntiAge↑, *eff↑, *Inflam↓, *AntiCan↑, *ROS↓, *Catalase↑, *GSR↑, *HO-1↑, *NAD↑, *NQO1↑, *SOD↑, *NRF2↑,
3078- RES,    The Effects of Resveratrol on Prostate Cancer through Targeting the Tumor Microenvironment
- Review, Pca, NA
*ROS↓, ROS↑, DNAdam↑, Apoptosis↑, Hif1a↑, Casp3↑, Casp9↑, Cyt‑c↑, Dose↝, MMPs↓, MMP2↓, MMP9↓, EMT↓, E-cadherin↑, N-cadherin↓, AR↓,
3079- RES,    Therapeutic role of resveratrol against hepatocellular carcinoma: A review on its molecular mechanisms of action
- Review, Var, NA
angioG↓, TumMeta↓, ChemoSen↑, NADPH↑, SIRT1↑, NF-kB↓, NLRP3↓, Dose↝, COX2↓, MMP9↓, PGE2↓, TIMP1↑, TIMP2↑, Sp1/3/4↓, p‑JNK↓, uPAR↓, ROS↓, CXCR4↓, IL6↓, Gli1↓, *ROS↓, *GSTs↑, *SOD↑, *Catalase↑, *GPx↑, *lipid-P↓, *GSH↑, eff↑, eff↑, eff↑,
3069- RES,    Resveratrol Inhibits NLRP3 Inflammasome-Induced Pyroptosis and miR-155 Expression in Microglia Through Sirt1/AMPK Pathway
- in-vitro, Nor, N9
*antiOx↑, *Inflam↓, *ROS↓, *NF-kB↓, *AMPK↑, *SIRT1↑, *miR-155↓, *NLRP3↓,
3064- RES,    Resveratrol Suppresses Cancer Cell Glucose Uptake by Targeting Reactive Oxygen Species–Mediated Hypoxia-Inducible Factor-1α Activation
- in-vitro, CRC, HT-29 - in-vitro, BC, T47D - in-vitro, Lung, LLC1
FDG↓, ROS↓, Hif1a↓, GLUT1↓, lactateProd↓,
3060- RES,    Resveratrol targeting NRF2 disrupts the binding between KEAP1 and NRF2-DLG motif to ameliorate oxidative stress damage in mice pulmonary infection
- in-vitro, Nor, RAW264.7 - in-vivo, NA, NA
*NRF2↑, *antiOx↑, *ROS↓,
3059- RES,    Resveratrol, an Nrf2 activator, ameliorates aging-related progressive renal injury
- in-vivo, Nor, HK-2
*RenoP↑, *Inflam↓, *NRF2↑, *HO-1↑, *SIRT1↑, *ROS↓, AntiAge↑,
3057- RES,    The therapeutic effect of resveratrol: Focusing on the Nrf2 signaling pathway
- Review, Var, NA - Review, AD, NA - Review, Stroke, NA
*NRF2↑, *Keap1↓, *ROS↓, *Apoptosis↓, *Inflam↓, *antiOx↑, *hepatoP↑, *neuroP↑, *cardioP↑, *RenoP↑, *AntiCan↑, *memory↑, *SOD↑, *GPx↑, *Catalase↑, *MDA↓, *NRF2↑, *HO-1↑, *ROS↓, *Aβ↓, *iNOS↓, *COX2↓, *GSH↑, *HO-1⇅, *SIRT1↑,
4288- RES,    Trans-resveratrol Inhibits Tau Phosphorylation in the Brains of Control and Cadmium Chloride-Treated Rats by Activating PP2A and PI3K/Akt Induced-Inhibition of GSK3β
- in-vivo, AD, NA
*memory↑, *GSH↑, *ROS↓, *MDA↓, *p‑tau↓, *PI3K↑, *Akt↑, *AMPK↑, *PP2A↑, *GSK‐3β↓,
4284- RES,    Resveratrol induces dephosphorylation of Tau by interfering with the MID1-PP2A complex
- in-vitro, AD, HEK293 - NA, Stroke, NA - in-vivo, AD, NA
*p‑tau↓, *PP2A↑, *neuroP↑, *antiOx↑, COX2↓, *AntiAg↑, *SIRT1↑, *AMPK↑, *Acetyl-CoA↓, *FAO↑, *ADAM10↑, *BACE↓, *Aβ↓, *memory↑, *Inflam↓, *ROS↓,
3613- RES,    Resveratrol for Alzheimer's disease
- Review, AD, NA
*SIRT1↑, *BioAv↝, *toxicity↓, *ROS↓, *antiOx↑, *Aβ↓, *MMP9↓, *TNF-α↓,
3612- RES,    Resveratrol in Alzheimer's disease: a review of pathophysiology and therapeutic potential
- Review, AD, NA
*other↑, *Aβ↓, *Inflam↓, *NF-kB↓, *neuroP↑, *HO-1↑, *lipid-P↓, *COX2↓, *AMPK↑, *Catalase↑, *SOD↑, *GSR↑, *ROS↓, *MMP9↓, *cognitive↑, *SIRT1↑, *IL1β↓, *IL6↓,
3099- RES,    Resveratrol and cognitive decline: a clinician perspective
- Review, Nor, NA - NA, AD, NA
*antiOx↑, *ROS↓, *cognitive↑, *neuroP↑, *SIRT1↑, *AMPK↑, *GPx↑, *HO-1↑, *GSK‐3β↑, *COX2↓, *PGE2↓, *NF-kB↓, *NO↓, *Casp3↓, *MMP3↓, *MMP9↓, *MMP↑, *GSH↑, *other↑, *BioAv↑, *memory↑, *GlutMet↑, *BioAv↓, *Half-Life↓, *toxicity∅,
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↓,
1511- RES,  Chemo,    Combination therapy in combating cancer
- Review, NA, NA
eff↑, *NRF2↑, *GSH↑, *ROS↓, chemoPv↑, ChemoSideEff↓,
2441- RES,    Anti-Cancer Properties of Resveratrol: A Focus on Its Impact on Mitochondrial Functions
- Review, Var, NA
*toxicity↓, *BioAv↝, *Dose↝, *hepatoP↑, *neuroP↑, *AntiAg↑, *COX2↓, *antiOx↑, *ROS↓, *ROS↑, PI3K↓, Akt↓, NF-kB↓, Wnt↓, β-catenin/ZEB1↓, NRF2↑, GPx↑, HO-1↑, BioEnh?, PTEN↑, ChemoSen↑, eff↑, mt-ROS↑, Warburg↓, Glycolysis↓, GlucoseCon↓, GLUT1↓, lactateProd↓, HK2↓, EGFR↓, cMyc↓, ROS↝, MMPs↓, MMP7↓, survivin↓, TumCP↓, TumCMig↓, TumCI↓,
2443- RES,    Health Benefits and Molecular Mechanisms of Resveratrol: A Narrative Review
- Review, Var, NA
*antiOx↑, *ROS↓, *PTEN↑, *Akt↓, *Catalase↑, *SOD↑, *ERK↓, *GSH↑, *AMPK↑, *FOXO1↝, *RNS↓, *Catalase↑, *cardioP↑, *PI3K↑, *eNOS↑, hepatoP↑,
2566- RES,    A comprehensive review on the neuroprotective potential of resveratrol in ischemic stroke
- Review, Stroke, NA
*neuroP↑, *NRF2↑, *SIRT1↑, *PGC-1α↑, *FOXO↑, *HO-1↑, *NQO1↑, *ROS↓, *BP↓, *BioAv↓, *Half-Life↝, *AMPK↑, *GSK‐3β↓, *eff↑, *AntiAg↑, *BBB↓, *Inflam↓, *MPO↓, *TLR4↓, *NF-kB↓, *p65↓, *MMP9↓, *TNF-α↓, *IL1β↓, *PPARγ↑, *MMP↑, *ATP↑, *Cyt‑c∅, *mt-lipid-P↓, *H2O2↓, *HSP70/HSPA5↝, *Mets↝, *eff↑, *eff↑, *motorD↑, *MDA↓, *NADH:NAD↑, eff↑, eff↑,
6056- RES,  SeNPs,    A comparative study of resveratrol and resveratrol-functional selenium nanoparticles: Inhibiting amyloid β aggregation and reactive oxygen species formation properties
- Study, AD, NA
*antiOx↑, *eff↑, *ROS↓, *Apoptosis↓, *Aβ↓,
6054- RES,  SeNPs,    Oral Administration of Resveratrol-Selenium-Peptide Nanocomposites Alleviates Alzheimer's Disease-like Pathogenesis by Inhibiting Aβ Aggregation and Regulating Gut Microbiota
- in-vivo, AD, NA
*Dose↝, *cognitive↑, *Aβ↓, *ROS↓, *TAC↑, *GutMicro↑, *BBB↑,
6051- RES,  SeNPs,  Chit,    Resveratrol-loaded selenium/chitosan nano-flowers alleviate glucolipid metabolism disorder-associated cognitive impairment in Alzheimer's disease
- in-vivo, AD, NA
*Inflam↓, *ROS↓, *GutMicro↑, *lipid-P↓, *Aβ↓, *tau↓, *cognitive↑,
4670- RES,  CUR,  EGCG,  TQ,    Targeting aging pathways with natural compounds: a review of curcumin, epigallocatechin gallate, thymoquinone, and resveratrol
- Review, Nor, NA
*antiOx↑, *Inflam↓, *AntiAge↑, *SIRT1↑, *SIRT3↑, *FOXO↑, *ROS↓,

Showing Research Papers: 1 to 27 of 27

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 27

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

GPx↑, 1,   HO-1↑, 2,   NRF2↑, 1,   ROS↓, 3,   ROS↑, 4,   ROS↝, 1,   mt-ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 1,   MMP↓, 1,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 1,   CRM↑, 1,   FDG↓, 1,   GlucoseCon↓, 1,   GlutMet↓, 1,   Glycolysis↓, 1,   HK2↓, 1,   lactateProd↓, 2,   NADPH↑, 1,   PFK↓, 1,   POLD1↓, 1,   SIRT1↑, 2,   Warburg↓, 1,  

Cell Death ⓘ

Akt↓, 2,   Apoptosis↑, 2,   Bcl-2↓, 1,   Casp3↑, 1,   Casp9↑, 1,   CK2↓, 1,   Cyt‑c↑, 1,   p‑JNK↓, 1,   survivin↓, 1,  

Kinase & Signal Transduction ⓘ

Sp1/3/4↓, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 2,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↓, 1,   p62↓, 2,   p62↑, 1,   TumAuto↓, 1,   TumAuto↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

CSCs↓, 1,   EMT↓, 2,   FOXO4↓, 1,   Gli1↓, 1,   IGF-1↓, 1,   mTOR↓, 1,   PI3K↓, 2,   PTEN↑, 1,   Wnt↓, 1,  

Migration ⓘ

E-cadherin↑, 2,   Fibronectin↓, 1,   Ki-67↓, 1,   MMP2↓, 2,   MMP7↓, 1,   MMP9↓, 3,   MMPs↓, 2,   N-cadherin↓, 1,   Slug↓, 1,   SMAD2↓, 1,   SMAD3↓, 1,   Snail↓, 1,   TGF-β↓, 1,   TIMP1↑, 1,   TIMP2↑, 1,   TumCI↓, 2,   TumCMig↓, 1,   TumCP↓, 3,   TumMeta↓, 2,   uPAR↓, 1,   Vim?, 1,   Zeb1↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   EGFR↓, 1,   Hif1a↓, 2,   Hif1a↑, 1,   VEGF↓, 1,  

Barriers & Transport ⓘ

GLUT1↓, 2,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   CRP↓, 1,   CXCR4↓, 1,   IL1β↓, 1,   IL6↓, 1,   NF-kB↓, 2,   PD-1↓, 1,   PGE2↓, 1,   Th1 response↑, 1,  

Protein Aggregation ⓘ

NLRP3↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Drug Metabolism & Resistance ⓘ

BioEnh?, 1,   ChemoSen↑, 2,   Dose↝, 2,   eff↑, 8,   RadioS↑, 1,  

Clinical Biomarkers ⓘ

AR↓, 1,   CRP↓, 1,   EGFR↓, 1,   IL6↓, 1,   Ki-67↓, 1,  

Functional Outcomes ⓘ

AntiAge↑, 1,   AntiCan↑, 1,   chemoPv↑, 1,   ChemoSideEff↓, 1,   hepatoP↑, 1,  

Infection & Microbiome ⓘ

CD8+↑, 1,  
Total Targets: 106

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 12,   Catalase↑, 7,   GPx↑, 3,   GSH↑, 6,   GSR↑, 2,   GSTs↑, 1,   H2O2↓, 1,   HO-1↑, 6,   HO-1⇅, 1,   Keap1↓, 2,   lipid-P↓, 3,   mt-lipid-P↓, 1,   MDA↓, 4,   Mets↝, 1,   MPO↓, 2,   NQO1↑, 2,   NRF2↑, 8,   RNS↓, 1,   ROS↓, 26,   ROS↑, 1,   SIRT3↑, 1,   SOD↑, 5,   TAC↑, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↑, 1,   Insulin↓, 1,   MMP↑, 2,   PGC-1α↑, 1,  

Core Metabolism/Glycolysis ⓘ

Acetyl-CoA↓, 1,   ALAT↓, 1,   AMPK↑, 8,   FAO↑, 1,   GlutMet↑, 1,   NAD↑, 1,   NADH:NAD↑, 1,   PPARγ↑, 1,   SIRT1↑, 11,  

Cell Death ⓘ

Akt↓, 1,   Akt↑, 1,   Apoptosis↓, 2,   Casp3↓, 1,   Cyt‑c∅, 1,   iNOS↓, 1,  

Transcription & Epigenetics ⓘ

other↑, 2,  

Protein Folding & ER Stress ⓘ

HSP70/HSPA5↝, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 1,   FOXO↑, 2,   FOXO1↝, 1,   GSK‐3β↓, 2,   GSK‐3β↑, 1,   mTOR↓, 1,   PI3K↑, 2,   PTEN↑, 1,  

Migration ⓘ

AntiAg↑, 3,   miR-155↓, 1,   MMP3↓, 1,   MMP9↓, 4,  

Angiogenesis & Vasculature ⓘ

eNOS↑, 1,   NO↓, 2,   VEGF↓, 1,  

Barriers & Transport ⓘ

BBB↓, 1,   BBB↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 4,   IL1β↓, 2,   IL6↓, 1,   Inflam↓, 13,   NF-kB↓, 5,   p65↓, 1,   PGE2↓, 1,   TLR4↓, 1,   TNF-α↓, 3,  

Synaptic & Neurotransmission ⓘ

AChE↓, 1,   ADAM10↑, 1,   tau↓, 1,   p‑tau↓, 2,  

Protein Aggregation ⓘ

Aβ↓, 8,   BACE↓, 1,   NLRP3↓, 1,   PP2A↑, 2,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   BioAv↑, 1,   BioAv↝, 2,   Dose↝, 3,   eff↑, 5,   Half-Life↓, 1,   Half-Life↝, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   AST↓, 1,   BP↓, 2,   GutMicro↑, 2,   IL6↓, 1,  

Functional Outcomes ⓘ

AntiAge↑, 3,   AntiCan↑, 2,   cardioP↑, 4,   cognitive↑, 5,   hepatoP↑, 3,   memory↑, 4,   motorD↑, 1,   neuroP↑, 8,   OS↑, 1,   RenoP↑, 2,   toxicity↓, 2,   toxicity∅, 1,   Weight↓, 1,  
Total Targets: 103

Scientific Paper Hit Count for: ROS, Reactive Oxygen Species
27 Resveratrol
4 Curcumin
3 Selenium NanoParticles
2 EGCG (Epigallocatechin Gallate)
1 Silver-NanoParticles
1 Chlorogenic acid
1 Quercetin
1 Calorie Restriction Mimetics
1 Hydroxycinnamic-acid
1 Spermidine
1 Aspirin -acetylsalicylic acid
1 Huperzine A/Huperzia serrata
1 Rivastigmine
1 Galantamine
1 Pterostilbene
1 Chemotherapy
1 chitosan
1 Thymoquinone
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#:275  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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