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


TumCCA, Tumor cell cycle arrest: Click to Expand ⟱
Source:
Type:
Tumor cell cycle arrest refers to the process by which cancer cells stop progressing through the cell cycle, which is the series of phases that a cell goes through to divide and replicate. This arrest can occur at various checkpoints in the cell cycle, including the G1, S, G2, and M phases. S, G1, G2, and M are the four phases of mitosis.
Scientific Papers found: Click to Expand⟱
3055- RES,    Resveratrol and Tumor Microenvironment: Mechanistic Basis and Therapeutic Targets
- Review, Var, NA
BioAv↓, Resveratrol is poorly bioavailable, and that considered the major hindrance to exert its therapeutic effect, especially for cancer management
BioAv↓, at lower doses (25 mg per healthy subject) demonstrate that the mean proportion of free resveratrol in plasma was 1.7–1.9% with a mean plasma concentration of free resveratrol around 20 nM
Dose↑, Boocock and his colleagues studied the pharmacokinetic of resveratrol; in vitro data showed that minimum of 5 µmol/L resveratrol is essential for the chemopreventive effects to be elicited
eff↑, Despite the low bioavailability of resveratrol, it shows efficacy in vivo. This may be due to the conversion of both glucuronides and sulfate back to resveratrol in target organs such as the liver
eff↑, repeated administration of high doses of resveratrol generates a higher plasma concentration of parent and a much higher concentration of sulfate and glucuronide conjugates in the plasma
Dose↑, The doses tested in this study were 0.5, 1.0, 2.5 or 5.0 g daily for 29 days. No toxicity was detected, but moderate gastrointestinal symptoms were reported for 2.5 and 5.0 g doses
BioAv↑, the co-administration of piperine with resveratrol was used to enhance resveratrol bioavailability
ROS↑, Recent studies have shown that resveratrol increases ROS generation and decreases mitochondrial membrane potential
MMP↓,
P21↑, treatment decreased the viability of melanoma cells by activating the expression of both p21 and p27, which promoted cell cycle arrest.
p27↑,
TumCCA↑,
ChemoSen↑, Additionally, the use of resveratrol with cisplatin in malignant human mesothelioma cells (MSTO-211H and H-2452 cells) synergistically induces cell death by increasing the intracellular ROS level [64].
COX2↓, covers the down-regulation of the products of the following genes, COX-2, 5-LOX, VEGF, IL-1, IL-6, IL-8, AR and PSA [93].
5LO↓,
VEGF↓,
IL1↓,
IL6↓,
IL8↓,
AR↓,
PSA↓,
MAPK↓, by preventing also the activation of the MAPK and PI3K/Akt signaling pathways, it suppresses HIF-1a and VEGF release in ovarian cancer cells of humans
Hif1a↓,
Glycolysis↓, Resveratrol was found to effectively impede the activation, invasion, migration and glycolysis of PSCs induced by reactive oxygen species (ROS) by down-regulating the expression of microRNA 21 (miR-21)
miR-21↓,
PTEN↑, also by increasing the phosphatise and tensin homolog (PTEN) protein levels
Half-Life↝, 25 mg/70 kg resveratrol administered to healthy human participants, the compound predominantly appeared in the form of glucuronide and sulfate conjugates in serum and urine and reached its peak concentrations in serum about 30 min after ingestion
*IGF-1↓, Brown and colleagues noted how a major decline in circulating insulin-like growth factor (IGF)-I as well as IGF-binding proteins (IGFBP-3) among healthy individuals can be credited to the intake of resveratrol
*IGFBP3↑,
Half-Life↓, Microactive® and Resveratrol SR and manufactured by Bioactives. This compound is capable of sustained release for over 12 h to increase intestinal residence time.

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↓, Treating A375SM cells with resveratrol resulted in a decrease in cell growth.
P21↑, resveratrol was observed to increase the gene expression levels of p21 and p27, as well as decrease the gene expression of cyclin B.
p27↑,
CycB↓,
ROS↑, generation of reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress were confirmed at the cellular and protein levels
ER Stress↑,
p‑p38↑, Resveratrol induced the ROS-p38-p53 pathway by increasing the gene expression of phosphorylated p38 mitogen-activated protein kinase
P53↑, while it induced the p53 and ER stress pathway by increasing the gene expression levels of phosphorylated eukaryotic initiation factor 2α and C/EBP homologous protein.
p‑eIF2α↑,
EP4↑,
CHOP↑,
Bcl-2↓, downregulating B-cell lymphoma-2 (Bcl-2) expression and upregulating Bcl-2-associated X protein expression
BAX↓,
TumCCA↑, Resveratrol induced cell cycle arrest of melanoma cell line
NRF2↓, the decrease in Nrf2 expression caused by resveratrol may prevent the development of such resistance and thereby increase the sensitivity of melanoma cells to chemotherapy.
ChemoSen↑,
GSH↓, (GSH/GSSG) ratio was not measured, it can easily be assumed that the increased ROS generation by resveratrol reduced the GSH/GSSG ratio compared with the control

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↓, The anticancer mechanisms of RES in regard to breast cancer include the inhibition of cell proliferation, and reduction of cell viability, invasion, and metastasis.
tumCV↓,
TumCI↓,
TumMeta↓,
*antiOx↑, antioxidative, cardioprotective, estrogenic, antiestrogenic, anti-inflammatory, and antitumor properties it has been used against several diseases, including diabetes, neurodegenerative diseases, coronary diseases, pulmonary diseases, arthritis, and
*cardioP↑,
*Inflam↑,
*neuroP↑,
*Keap1↓, RES administration resulted in a downregulation of Keap1 expression, therefore, inducing Nrf2 signaling, and leading to a decrease in oxidative damage
*NRF2↑,
*ROS↓,
p62↓, decrease the severity of rheumatoid arthritis by inducing autophagy via p62 downregulation, decreasing the levels of interleukin-1β (IL-1β) and C-reactive protein as well as mitigating angiopoietin-1 and vascular endothelial growth factor (VEGF) path
IL1β↓,
CRP↓,
VEGF↓,
Bcl-2↓, RES downregulates the levels of Bcl-2, MMP-2, and MMP-9, and induces the phosphorylation of extracellular-signal-regulated kinase (ERK)/p-38 and FOXO4
MMP2↓,
MMP9↓,
FOXO4↓,
POLD1↓, The in vivo experiment involving a xenograft model confirmed the ability of RES to reduce tumor growth via POLD1 downregulation
CK2↓, RES reduces the expression of casein kinase 2 (CK2) and diminishes the viability of MCF-7 cells.
MMP↓, Furthermore, RES impairs mitochondrial membrane potential, enhances ROS generation, and induces apoptosis, impairing BC progression
ROS↑,
Apoptosis↑,
TumCCA↑, RES has the capability of triggering cell cycle arrest at S phase and reducing the number of 4T1 BC cells in G0/G1 phase
Beclin-1↓, RES administration promotes cytotoxicity of DOX against BC cells by downregulating Beclin-1 and subsequently inhibiting autophagy
Ki-67↓, Reducing the Ki-67
ATP↓, RES’s administration is responsible for decreasing ATP production and glucose metabolism in MCF-7 cells.
GlutMet↓,
PFK↓, RES decreased PFK activity, preventing glycolysis and glucose metabolism in BC cells and decreasing cellular growth rate
TGF-β↓, RES (12.5–100 µM) inhibited TGF-β signaling and reduced the expression levels of its downstream targets that include Smad2 and Smad3 and as a result impaired the progression of BC cells.
SMAD2↓,
SMAD3↓,
Vim?, a significant decrease in the levels of vimentin, Snail1 and Slug occurred, while E-cadherin levels increased to suppress EMT and metastasis of BC cells.
Snail↓,
Slug↓,
E-cadherin↑,
EMT↓,
Zeb1↓, a significant decrease in the levels of vimentin, Snail1 and Slug occurred, while E-cadherin levels increased to suppress EMT and metastasis of BC cells.
Fibronectin↓,
IGF-1↓, RES administration (10 and 20 µM) impaired the migration and invasion of BC cells via inhibiting PI3K/Akt and therefore decreasing IGF-1 expression and preventing the upregulation of MMP-2
PI3K↓,
Akt↓,
HO-1↑, The activation of heme oxygenase-1 (HO-1) signaling by RES reduced MMP-9 expression and prevented metastasis of BC cells
eff↑, RES-loaded gold nanoparticles were found to enhance RES’s ability to reduce MMP-9 expression as compared to RES alone
PD-1↓, RES inhibited PD-1 expression to promote CD8+ T cell activity and enhance Th1 immune responses.
CD8+↑,
Th1 response↑,
CSCs↓, RES has the ability to target CSCs in various tumors
RadioS↑, RES in reversing drug resistance and radio resistance.
SIRT1↑, RES administration (12.5–200 µmol/L) promotes sensitivity of BC cells to DOX by increasing Sirtuin 1 (SIRT1) expression
Hif1a↓, downregulating HIF-1α expression, an important factor in enhancing radiosensitivity
mTOR↓, mTOR suppression

884- RES,  PS,    Resveratrol and Pterostilbene Exhibit Anticancer Properties Involving the Downregulation of HPV Oncoprotein E6 in Cervical Cancer Cells
- in-vitro, Cerv, HeLa
TumCD↑, pterostilbene displayed a 1.97-fold lower IC50 than Res
TumCCA↑, S-phase cell cycle arrest (both)
E6↓, Downregulation of HPV Oncoprotein E6
Casp3↑,
P53↑,

1490- RES,    Anticancer Potential of Resveratrol, β-Lapachone and Their Analogues
- Review, Var, NA
TumCCA↑, lapachone and its iodine derivatives induce cell cycle arrest in G2/M in human oral squamous cell carcinoma cells
ROS↑, The primary mechanism of action of β-lapachone and its derivatives is the formation of ROS [92] through its processing by NAD(P)H quinone oxidoreductase 1 (NQO1).
Ca+2↑, abnormal production of ROS leads to an increase in Ca++
MMP↓, depolarization of the mitochondrial membrane
ATP↓, decrease in ATP synthesis
TOP1?, β-lapachone inhibits the catalytic activity of topoisomerase I
P53↑, including upregulation of the p53 tumor suppressor protein
p53 Wildtype∅,
Akt↓, inactivation of the Akt/mTOR pathway was again attributed to β-lapachone, promoting the inhibition of EMT transition in NQO1-positive cells.
mTOR↓,
EMT↓,
*BioAv↓, β-lapachone is a promising anticancer drug, its low bioavailability represents a limitation for clinical use due to low solubility in water and gastrointestinal fluids

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.

924- RES,    Resveratrol sequentially induces replication and oxidative stresses to drive p53-CXCR2 mediated cellular senescence in cancer cells
- in-vitro, OS, U2OS - in-vitro, Lung, A549
TumCCA↑, S-phase arrest, which is commonly observed in cells treated with RSV
ROS↑,
γH2AX↑, remarkable increase in the amount of γ-H2AX, a marker for DNA double-strand breaks
ATM↑, a master regulator of DNA damage response, was activated by RSV
p‑CHK1↑,
cellSen↑,
CXCR2↑, peaks at day 5 then drops

883- RES,    Targeting Histone Deacetylases with Natural and Synthetic Agents: An Emerging Anticancer Strategy
HDAC↓, Res is a naturally occurring HDACi
TumCCA↑, HDACi exhibit their antitumor effect by the activation of cell cycle arrest, induction of apoptosis and autophagy, angiogenesis inhibition, increased reactive oxygen species generation causing oxidative stress, and mitotic cell death in cancer cells.
Apoptosis↑,
angioG↓,
ROS↑,

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↓, Resveratrol is also an Histone deacetylase inhibitors
TumCCA↑,
TumAuto↑,
angioG↓,
iNOS↓, inhibit iNOS expression in colon cancer cells

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

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: 11

Results for Effect on Cancer/Diseased Cells:
5LO↓,1,   Akt↓,3,   angioG↓,2,   AntiTum↑,1,   Apoptosis↑,4,   AR↓,1,   ATM↑,1,   ATP↓,2,   ATP↑,1,   BAX↓,1,   BAX↑,1,   Bcl-2↓,3,   Bcl-xL↓,2,   Beclin-1↓,1,   BioAv↓,2,   BioAv↑,1,   Ca+2↑,1,   Ca+2↝,1,   Casp3↑,2,   Casp9↑,1,   CD8+↑,1,   cellSen↑,1,   ChemoSen↑,2,   p‑CHK1↑,1,   CHOP↑,1,   CK2↓,1,   COX2↓,1,   CRP↓,1,   CSCs↓,1,   CXCR2↑,1,   cycA1↑,1,   CycB↓,1,   cycD1↓,2,   cycD1↑,1,   cycE↑,1,   Dose↑,2,   E-cadherin↑,1,   E6↓,1,   ECAR↓,1,   eff↑,3,   p‑eIF2α↑,1,   EMT↓,2,   EP4↑,1,   ER Stress↑,1,   Fibronectin↓,1,   FOXO4↓,1,   GlutMet↓,1,   Glycolysis↓,2,   GSH↓,1,   Half-Life↓,1,   Half-Life↝,1,   HDAC↓,2,   Hif1a↓,2,   HO-1↑,1,   IGF-1↓,1,   IGF-1R↓,1,   IL1↓,1,   IL1β↓,1,   IL6↓,1,   IL8↓,1,   iNOS↓,1,   Ki-67↓,1,   lactateProd↓,1,   MAPK↓,1,   Mcl-1↓,1,   MDM2↓,1,   miR-21↓,1,   MMP↓,3,   MMP2↓,1,   MMP9↓,1,   mTOR↓,2,   NAF1↓,1,   NRF2↓,1,   NRF2↑,1,   OCR↑,1,   other↓,1,   OXPHOS↑,1,   P21↑,2,   p27↑,3,   p‑p38↑,1,   P53↑,5,   p53 Wildtype∅,1,   p62↓,1,   cl‑PARP↑,1,   PD-1↓,1,   PDH↑,1,   PFK↓,1,   PI3K↓,1,   POLD1↓,1,   PPP↓,1,   PSA↓,1,   PTEN↑,1,   RadioS↑,1,   ROS↑,7,   SIRT1↑,1,   Slug↓,1,   SMAD2↓,1,   SMAD3↓,1,   Snail↓,1,   Sp1/3/4↓,1,   TGF-β↓,1,   Th1 response↑,1,   TOP1?,1,   TumAuto↑,1,   TumCCA↑,11,   TumCD↑,1,   TumCG↓,2,   TumCI↓,1,   TumCP↓,3,   tumCV↓,1,   TumMeta↓,1,   VEGF↓,2,   Vim?,1,   Wnt↓,1,   Zeb1↓,1,   β-catenin/ZEB1↓,1,   γH2AX↑,1,  
Total Targets: 117

Results for Effect on Normal Cells:
antiOx↑,1,   BioAv↓,1,   cardioP↑,1,   ECAR∅,1,   IGF-1↓,1,   IGFBP3↑,1,   Inflam↑,1,   Keap1↓,1,   neuroP↑,1,   NRF2↑,1,   other?,1,   ROS↓,1,  
Total Targets: 12

Scientific Paper Hit Count for: TumCCA, Tumor cell cycle arrest
11 Resveratrol
1 Pterostilbene
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:141  Target#:322  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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