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


RadioS, RadioSensitizer: Click to Expand ⟱
Source:
Type:
A radiosensitizer is an agent that makes cancer cells more sensitive to the damaging effects of radiation therapy. By using a radiosensitizer, clinicians aim to enhance the effectiveness of radiation treatment by either increasing the damage incurred by tumor cells or by interfering with the cancer cells’ repair mechanisms. This can potentially allow for lower doses of radiation, reduced side effects, or improved treatment outcomes.
Pathways that help Radiosensitivity: downregulating HIF-1α, increase SIRT1, Txr

List of Natural Products with radiosensitizing properties:
-Curcumin:modulate NF-κB, STAT3 and has been shown in preclinical studies to enhance the effects of radiation by inhibiting cell survival pathways.
-Resveratrol:
-EGCG:
-Quercetin:
-Genistein:
-Parthenolide:

How radiosensitizers inhibit the thioredoxin (Trx) system in cellular contexts. Notable radiosensitizers, including:
-gold nanoparticles (GNPs),
-gold triethylphosphine cyanide ([Au(SCN) (PEt3)]),
-auranofin, ceria nanoparticles (CONPs),
-curcumin and its derivatives,
-piperlongamide,
-indolequinone derivatives,
-micheliolide,
-motexafin gadolinium, and
-ethane selenide selenidazole derivatives (SeDs)
Scientific Papers found: Click to Expand⟱
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

3076- RES,    Resveratrol for targeting the tumor microenvironment and its interactions with cancer cells
- Review, Var, NA
IL6↓, A dose-dependent reduction of IL-6 by resveratrol led to attenuation of matrix metalloproteinases (MMPs), including MMP2 and MMP9
MMPs↓,
MMP2↓,
MMP9↓,
BioAv↓, The most important weakness of the usual form of resveratrol is its low absorption in the intestine and its low bioavailability
Half-Life↑, some covers such as liposomes and micelles also can facilitate absorption and increase half-life
BioAv↑, another study showed that carboxymethyl chitosan can increase bioavailability by more than 3.5 times
Dose↝, low concentrations of resveratrol (lower than 50 uM) cause no remarkable toxicity for normal cells, while higher concentrations are associated with increased oxidative injury
angioG↓, It is suggested that inhibition of STAT3, IL-10, and a reduction of vascular endothelial growth factor (VEGF) by resveratrol is involved in the suppression of macrophages and reduction of invasion and angiogenesis
IL10↓,
VEGF↓,
NF-kB↓, Inhibition of NF-kB by resveratrol can attenuate the expression of COX-2.
COX2↓,
SIRT1↑, Activation of Sirt-1 by resveratrol has a role in the suppression of NF-kB
Wnt↓, Resveratrol has also been shown that inhibit the Wnt/C-Myc pathway too
cMyc↓,
STAT3↓, Resveratrol has been shown that attenuate the expression of STAT3 through reduction of IL-6 level
PTEN↑, Downregulation of miR-17, miR-20a and miR-106b by resveratrol can activate PTEN, which leads to suppression of PI3K and induction of apoptosis in cancer cells
ROS↑, Resveratrol can trigger NOX5-induced ROS, leading to the induction of DNA damage and cancer cells senescence
RadioS↑, The combination of radiation and resveratrol has shown that has a synergic effect for stimulation of ROS production and induction of senescence in non-small cell lung carci- noma
Hif1a↓, Resveratrol can inhibit HIF-1α and its downstream proteins, including E-cadherin and vimentin
E-cadherin↓,
Vim↓,
angioG↓, Furthermore, resveratrol inhibits angiogenesis markers and tumor growth through the inhibition of HIF-1a

2687- RES,    Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs
- Review, NA, NA - Review, AD, NA
NF-kB↓, RES affects NF-kappaB activity and inhibits cytochrome P450 isoenzyme (CYP A1) drug metabolism and cyclooxygenase activity.
P450↓,
COX2↓,
Hif1a↓, RES may inhibit also the expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) and thus may have anti-cancer properties
VEGF↓,
*SIRT1↑, RES induces sirtuins, a class of proteins involved in regulation of gene expression. RES is also considered to be a SIRT1-activating compound (STACs).
SIRT1↓, In contrast, decreased levels of SIRT1 and SIRT2 were observed after treatment of BJ cells with concentrations of RES
SIRT2↓,
ChemoSen⇅, However, the effects of RES remain controversial as it has been reported to increase as well as decrease the effects of chemotherapy.
cardioP↑, RES has been shown to protect against doxorubicin-induced cardiotoxicity via restoration of SIRT1
*memory↑, RES has been shown to inhibit memory loss and mood dysfunction which can occur during aging.
*angioG↑, RES supplementation resulted in improved learning in the rats. This has been associated with increased angiogenesis and decreased astrocytic hypertrophy and decreased microglial activation in the hippocampus.
*neuroP↑, RES may have neuroprotective roles in AD and may improve memory function in dementia.
STAT3↓, RES was determined to inhibit STAT3, induce apoptosis, suppress the stemness gene signature and induced differentiation.
CSCs↓,
RadioS↑, synergistically increased radiosensitivity. RES treatment suppressed repair of radiation-induced DNA damage
Nestin↓, RES decreased NESTIN
Nanog↓, RES was determined to suppress the expression of NANOG
TP53↑, RES treatment activated TP53 and p21Cip1.
P21↑,
CXCR4↓, RES downregulated nuclear localization and activity of NF-kappa-B which resulted in decreased expression of MMP9 and C-X-C chemokine receptor type 4 (CXCR4), two proteins associated with metastasis.
*BioAv↓, The pharmacological properties of RES can be enhanced by nanoencapsulation. Normally the solubility and stability of RES is poor.
EMT↓, RES was determined to suppress many gene products associated with EMT such as decreased vimentin and SLUG expression but increased E-cadherin expression.
Vim↓,
Slug↓,
E-cadherin↑,
AMPK↑, RES can induce AMPK which results in inhibition of the drug transporter MDR1 in oxaliplatin-resistant (L-OHP) HCT116/L-OHP CRCs.
MDR1↓,
DNAdam↑, RES induced double strand DNA breaks by interfering with type II topoisomerase.
TOP2↓, The DNA damage was determined to be due to type II topoisomerase poisoning.
PTEN↑, RES was determined to upregulate phosphatase and tensin homolog (PTEN) expression and decrease the expression of activated Akt.
Akt↓,
Wnt↓, RES was shown to decrease WNT/beta-catenin pathway activity and the downstream targets c-Myc and MMP-7 in CRC cells.
β-catenin/ZEB1↓,
cMyc↓,
MMP7↓,
MALAT1↓, RES also decreased the expression of long non-coding metastasis associated lung adenocarcinoma transcript 1 (RNA-MALAT1) in the LoVo and HCT116 CRC cells.
TCF↓, Treatment of CRC cells with RES resulted in decreased expression of transcription factor 4 (TCF4), which is a critical effector molecule of the WNT/beta-catenin pathway.
ALDH↓, RES was determined to downregulate ALDH1 and CD44 in HNC-TICs in a dose-dependent fashion.
CD44↓,
Shh↓, RES has been determined to decrease IL-6-induced Sonic hedgehog homolog (SHH) signaling in AML.
IL6↓, RES has been shown to inhibit the secretion of IL-6 and VEGF from A549 lung cancer cells
VEGF↓,
eff↑, Combined RES and MET treatment resulted in a synergistic response in terms of decreased TP53, gammaH2AX and P-Chk2 expression. Thus, the combination of RES and MET might suppress some of the aging effects elicited by UVC-induced DNA damage
HK2↓, RES treatment resulted in a decrease in HK2 and increased mitochondrial-induced apoptosis.
ROS↑, RES was determined to shut off the metabolic shift and increase ROS levels and depolarized mitochondrial membranes.
MMP↓,

1492- RES,    Resveratrol: Biological and pharmaceutical properties as anticancer molecule
- Review, Var, NA
RadioS↑,
ChemoSen↑,

1491- RES,    Resveratrol Augments Doxorubicin and Cisplatin Chemotherapy: A Novel Therapeutic Strategy
RadioS↑,
ChemoSen↑,

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


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 6

Results for Effect on Cancer/Diseased Cells:
Akt↓,2,   ALDH↓,1,   AMPK↑,1,   angioG↓,2,   Apoptosis↑,1,   ATP↓,1,   BAX↑,1,   Bcl-2↓,2,   Beclin-1↓,1,   BioAv↓,1,   BioAv↑,1,   cardioP↑,1,   CD44↓,1,   CD8+↑,1,   ChemoSen↑,3,   ChemoSen⇅,1,   CK2↓,1,   cMyc↓,2,   COX2↓,3,   CRP↓,1,   CSCs↓,2,   CXCR4↓,1,   cycD1↓,1,   DNAdam↑,1,   Dose↝,1,   E-cadherin↓,1,   E-cadherin↑,2,   eff↑,2,   EMT↓,2,   FasL↓,1,   Ferroptosis↑,1,   Fibronectin↓,1,   FOXO4↓,1,   FOXP3↓,1,   GlutMet↓,1,   GPx4↓,1,   Half-Life↑,1,   Hif1a↓,3,   HK2↓,1,   HLA↑,1,   HO-1↑,1,   IGF-1↓,1,   IL10↓,1,   IL1β↓,1,   IL6↓,2,   Ki-67↓,1,   lipid-P↑,1,   MALAT1↓,2,   MDR1↓,1,   MMP↓,2,   MMP2↓,2,   MMP7↓,1,   MMP9↓,2,   MMPs↓,1,   mTOR↓,1,   Nanog↓,1,   Nestin↓,1,   NF-kB↓,2,   p‑NF-kB↓,1,   P21↑,1,   P450↓,1,   p62↓,1,   PD-1↓,1,   PFK↓,1,   PI3K↓,1,   POLD1↓,1,   PTEN↑,2,   RadioS↑,6,   ROS↑,3,   Shh↓,1,   SIRT1↓,1,   SIRT1↑,2,   SIRT2↓,1,   Slug↓,2,   SMAD2↓,1,   SMAD3↓,1,   Snail↓,1,   STAT3↓,2,   TCF↓,1,   TGF-β↓,1,   Th1 response↑,1,   TOP2↓,1,   TP53↑,1,   TumCCA↑,1,   TumCI↓,1,   TumCP↓,1,   tumCV↓,1,   TumMeta↓,1,   VEGF↓,4,   Vim?,1,   Vim↓,2,   Wnt↓,2,   xCT↓,1,   Zeb1↓,1,   β-catenin/ZEB1↓,1,  
Total Targets: 95

Results for Effect on Normal Cells:
angioG↑,1,   antiOx↑,1,   BioAv↓,2,   BioAv↑,2,   cardioP↑,1,   Inflam↑,1,   Keap1↓,1,   memory↑,1,   neuroP↑,2,   NRF2↑,1,   ROS↓,1,   SIRT1↑,1,  
Total Targets: 12

Scientific Paper Hit Count for: RadioS, RadioSensitizer
6 Resveratrol
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:141  Target#:1107  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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