condition found tbRes List
EA, Ellagic acid: Click to Expand ⟱
Features:
Polyphenol found in fruits, vegetables, nuts and some mushrooms. Strawberries, raspberries, blackberries, cherries and walnuts, green tea and red wine.

- Ellagitannins are high molecular weight polyphenols with a complex structure that includes one or more HHDP groups attached to a sugar.
- Ellagic Acid is the simpler, bioactive compound released when the HHDP groups in ellagitannins cyclize during hydrolysis.

Pathways:
Apoptosis Regulation: (Bax, Bad) (Bcl-2, Bcl-xL)
Cell Cycle Arrest: G0/G1 or G2/M phases)
NF-κB (inhibit):
MAPK Pathways: (including ERK1/2, JNK, and p38 MAPK)
PI3K/Akt/mTOR: might downregulate this pathway
p53 Pathway: may influence the expression or activation of p53
Oxidative Stress and Nrf2 Pathway:exhibits antioxidant properties, <ROS, modulate the Nrf2 Angiogenesis Inhibition

Summary:
- Anti-oxidant, with some evidence it can induce ROS in cancer (production of ROS)
- Works well with Curcumin
- Reduced the viability of cancer cells at a concentration of 10 µmol/L, while in healthy cells, this effect was observed only at a concentration of 200 µmol/L
- Pomegranate juice (PJ) (180 ml) containing EA (25 mg) and ETs (318 mg, as punicalagins, the major fruit ellagitannin). Plasma concentration (31.9 ng/ml) after 1 h post-ingestion but was rapidly eliminated by 4 h. (Hence might be difficult to consume enough EA!!!! to match vitro requirements)
- Likely need > 10mg/kg/day -> *180kg = 1800mg (might be possible)
- Increased the expression of p53 and p21 proteins as well as markers of apoptosis (Bax and caspase-3), and decreases Bcl-2, NF-кB, and iNOS
- EA has restricted bioavailability, primarily due to its hydrophobic nature and very low water solubility.
- Industrial processing of pomegranates for juice production increases the concentration of EA in juices, but freezing reduces concentration

Punica granatum L. Pomegranate 700mg/kg (arils), 38700mg/kg(mesocarp)
Rubus idaeus L. Raspberry 2637–3309mg/kg
jaglandaceae Walnut 410mg/kg(freeEA) 8230mg/kg(totalEA)
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.

"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: 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: 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:regulates the expression of antioxidant genes. Inhibiting SIRT1 can increase ROS levels
• AMPK: regulates energy metabolism and can increase ROS levels when activated.
• mTOR: regulates cell growth and metabolism. Inhibiting mTOR can increase ROS levels
• HSP90: 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 Melavonate 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
-Lycopene typically 100mg/day range

Dual Role of Reactive Oxygen Species and their Application in Cancer Therapy

Scientific Papers found: Click to Expand⟱
1609- CUR,  EA,    Curcumin and Ellagic acid synergistically induce ROS generation, DNA damage, p53 accumulation and apoptosis in HeLa cervical carcinoma cells
- in-vitro, Cerv, NA
eff↑, combination of Curcumin and Ellagic acid at various concentrations showed better anticancer properties than either of the drug when used alone as evidenced by MTT assay
Dose∅, IC50 value for Curcumin is calculated as 16.52 mM and for Ellagic acid the IC50 Value is 19.47 mM. The combination of Curcumin and Ellagic acid has IC50 value 10.9 mM.
ROS↑, Curcumin alone increases the ROS level significantly. Similarly the C + E treated cells exhibited a very high magnitude of ROS level.
DNAdam↑, Curcumin and Ellagic acid show mild degree of DNA damage at this concentration but the C + E treated cells shows greater degree of DNA damage
P53↑, C + E treated cells show greater degree of stabilization of p53
P21↑, Elevated expression of p21 in response to Curcumin and C + E treatment
BAX↑, But the C + E treated cells showed higher expression of Bax
Dose∅, Curcumin daily shows detectable levels of Curcumin in plasma and urine and the concentration is close to 11.1 nMol/l

1621- EA,    The multifaceted mechanisms of ellagic acid in the treatment of tumors: State-of-the-art
- Review, Var, NA
AntiCan↑, Studies have shown its anti-tumor effect in gastric cancer, liver cancer, pancreatic cancer, breast cancer, colorectal cancer, lung cancer and other malignant tumors
Apoptosis↑,
TumCP↓,
TumMeta↓,
TumCI↓,
TumAuto↑,
VEGFR2↓, inhibition of VEGFR-2 signaling
MAPK↓, MAPK and PI3K/Akt pathways
PI3K↓,
Akt↓,
PD-1↓, Downregulation of VEGFR-2 and PD-1 expression
NOTCH↓, Inhibition of Akt and Notch
PCNA↓, regulation of the expression of proliferation-related proteins PCNA, Ki67, CyclinD1, CDK-2, and CDK-6
Ki-67↓,
cycD1↓,
CDK2↑,
CDK6↓,
Bcl-2↓,
cl‑PARP↑, up-regulated the expression of cleaved PARP, Bax, Active Caspase3, DR4, and DR5
BAX↑,
Casp3↑,
DR4↑,
DR5↑,
Snail↓, down-regulated the expression of Snail, MMP-2, and MMP-9
MMP2↓,
MMP9↓,
TGF-β↑, up-regulation of TGF-β1
PKCδ↓, Inhibition of PKC signaling
β-catenin/ZEB1↓, decreases the expression level of β-catenin
SIRT1↓, down-regulates the expression of anti-apoptotic protein, SIRT1, HuR, and HO-1 protein
HO-1↓,
ROS↑, up-regulates ROS
CHOP↑, activating the CHOP signaling pathway to induce apoptosis
Cyt‑c↑, releases cytochrome c
MMP↓, decreases mitochondrial membrane potential and oxygen consumption,
OCR↓,
AMPK↑, activates AMPK, and downregulates HIF-1α expression
Hif1a↓,
NF-kB↓, inhibition of NF-κB pathway
E-cadherin↑, Upregulates E-cadherin, downregulates vimentin and then blocks EMT progression
Vim↓,
EMT↓,
LC3II↑, Up-regulation of LC3 – II expression and down-regulation of CIP2A
CIP2A↓,
GLUT1↓, regulation of glycolysis-related gene GLUT1 and downstream protein PDH expression
PDH↝,
MAD↓, Downregulation of MAD, LDH, GR, GST, and GSH-Px related protein expressio
LDH↓,
GSTs↑,
NOTCH↓, inhibited the expression of Akt and Notch protein
survivin↓, survivin and XIAP was also significantly down-regulated
XIAP↓,
ER Stress↑, through ER stress
ChemoSideEff↓, could improve cisplatin-induced hepatotoxicity in colorectal cancer cells
ChemoSen↑, Enhancing chemosensitivity

1620- EA,  Rad,    Radiosensitizing effect of ellagic acid on growth of Hepatocellular carcinoma cells: an in vitro study
- in-vitro, Liver, HepG2
ROS↑, Treatment of HepG2 cells with EA and gamma radiation showed increased reactive oxygen species generation
P53↑, up regulation of p53 protein expression
TumCCA↑, combination treatment increased G2/M phase cell population
IL6↓, decreased IL-6, COX–2 and TNF-α expression
COX2↓,
TNF-α↓,
MMP↓, caused a loss in mitochondrial membrane potential
angioG↓, decreased level of angiogenesis marker MMP-9
MMP9↓,
BAX↑,
Casp3↑,
Apoptosis↑,
RadioS↑,
TBARS↑, EA increased TBARS level in HepG2 cells after irradiation
GSH↓, EA decreased the reduced glutathione content in HepG2 cells after irradiation
Bax:Bcl2↑, Combination treatment increased the Bax/Bcl2 ratio
p‑NF-kB↓, EA along with radiation decreased p-NF-κB level in tumour cells
p‑STAT3↓, Radiation and EA combination treatment decreased p-STAT3 level in tumour cells

1615- EA,    Absorption, metabolism, and antioxidant effects of pomegranate (Punica granatum l.) polyphenols after ingestion of a standardized extract in healthy human volunteers
- Human, Nor, NA
*BioAv∅, 800 mg of extract. Results indicate that ellagic acid (EA) from the extract is bioavailable, with an observed C(max) of 33 ng/mL at t(max) of 1 h.
*ROS∅, whereas the generation of reactive oxygen species (ROS) was not affected

1613- EA,    Ellagitannins in Cancer Chemoprevention and Therapy
- Review, Var, NA
ROS↑, pomegranate ET inhibit pro-inflammatory pathways including, but not limited to, the NF-κB pathway, whose activation leads to immune reactions, inflammation, and the transcription of genes involved in cell survival, such as Bclx and inhibitors of apop
angioG↓, ET to inhibit angiogenesis
ChemoSen↑, ET could also be utilized to increase the sensitivity of tumor cells to standard chemotherapeutic drugs
BAX↑, induction of pro-apoptotic mediators (Bax and Bak), downregulation of Bcl-2 and Bcl-XL, and reduced expression of cyclin-dependent kinases 2, 4, 6, and cyclins D1, D2, and E
Bak↑,
Bcl-2↓,
Bcl-xL↓,
CDK2↓,
CDK4↓,
CDK6↓,
cycD1↓,
cycE1↓,
TumCG↓, reduced LNCaP prostate cancer xenograft size, tumor vessel density, VEGF peptide levels and HIF-α expression after four weeks of treatment in severe combined immunodeficient mice
VEGF↓,
Hif1a↓,
eff↑, Oenothein B, a macrocyclic ET, and quercetin-3-O-glucuronide from Epilobium sp. herbs—used in traditional medicine to treat benign prostatic hyperplasia and prostatic adenoma—have been proven to strongly inhibit the proliferation of human prostate ca
COX2↓, pomegranate ET (i.e., punicalagin and ellagic acid) have been shown to suppress cyclooxygenase-2 (COX-2) protein expression in human colon cancer (HT-29) cells
TumCCA↑, pomegranate ET and their metabolites, i.e., urolithins A and C, inhibit HT-29 cells proliferation via G0/G1 and G2/M arrest
selectivity↑, interestingly, normal human breast epithelial cells (MCF-10A) were far less sensitive to the inhibitory effect of polyphenol-rich fractions.
Wnt/(β-catenin)↓, suppression of Wnt/β-catenin
*toxicity∅, LD50 of a standardized pomegranate fruit extract containing 30% punicalagin in Wistar rats was >5 g/kg b.w.,

1612- EA,    Negative Effect of Ellagic Acid on Cytosolic pH Regulation and Glycolytic Flux in Human Endometrial Cancer Cell
- in-vitro, EC, NA
NHE1↓, 48 hour treatment with Ellagic acid (20 µM) significantly decreased NHE1 transcript levels by 75%, NHE1 protein abundance by 95%
i-pH↓, pHi from 7.24 ± 0.01 to 7.02 ± 0.01
ROS↓, ROS by 82%
GlucoseCon↓, glucose uptake by 58%
NHE1↓, Treatment with EA is followed by a significant decline of NHE1 transcript levels, NHE1 protein abundance, and Na+/H+ exchanger activity.
Glycolysis↓, EA down-regulates expression and function of the Na+/H+ exchanger, decreases cytosolic acidification with subsequent impairment of glycolysis

1611- EA,    Targeting Myeloperoxidase Activity and Neutrophil ROS Production to Modulate Redox Process: Effect of Ellagic Acid and Analogues
- in-vitro, Mal, NA
*BioAv↓, ellagic acid is widely studied due to its antioxidant and parasite-inhibiting properties. However, its low oral bioavailability remains a concern
eff↑, very effective inhibitor of Plasmodium falciparum, showing an in vitro activity ranging from 100 to 300 nM
*BioAv↓, ellagic acid remains its very low oral bioavailability (<30% in mice), which impedes its use as an oral antimalarial drug and was partially linked to its low hydrosolubility.
ROS↑, when in contact with the parasite environment, could become pro-oxidant and efficient

1610- EA,    Anticancer Effect of Pomegranate Peel Polyphenols against Cervical Cancer
- Review, Cerv, NA
TumCCA↑, EA had a dose-dependent apoptotic effect on HeLa cells caused by cell cycle arrest in the G1 phase via the regulation of STAT3
STAT3↓,
P21↑, increase in the expression of both p21 mRNA and protein
IGFBP7↑, increase in igfb7
Akt↓, inhibition of the Akt/mTOR signaling
mTOR↓,
ROS↑, increase in the production of ROS and DNA damage
DNAdam↑,
P53↑, restored activity of p53 and p21 genes and
P21↑,
BAX↑, increased expression of the Bax

1608- EA,    Ellagic Acid from Hull Blackberries: Extraction, Purification, and Potential Anticancer Activity
- in-vitro, Cerv, HeLa - in-vitro, Liver, HepG2 - in-vitro, BC, MCF-7 - in-vitro, Lung, A549 - in-vitro, Nor, HUVECs
eff↑, Hull blackberry fruits into five growth periods according to color and determined the EA content in the fruits in each period. The EA content in the green fruit stage was the highest at 5.67 mg/g FW
Dose∅, EA inhibited HeLa cells with an IC50 of 35 μg/mL
*BioAv↑, EA is not sensitive to high temperatures and is not highly soluble in many solvents.
selectivity↑, selectivity index varied from 7.4 for Hela to about 1 for A549
TumCP↓, EA reduced the proliferation of human cervical cancer HeLa, SiHa, and C33A cells in a dose- and time-dependent manner, and the inhibitory effect was significantly more pronounced in HeLa cells than in SiHa and C33A cells
Casp↑, EA reduced the proliferation of human cervical cancer HeLa, SiHa, and C33A cells in a dose- and time-dependent manner, and the inhibitory effect was significantly more pronounced in HeLa cells than in SiHa and C33A cells
PTEN↑,
TSC1↑,
mTOR⇅,
Akt↓, AKT, PDK1 expression were down-regulated
PDK1↓,
E6↓, mRNA levels of E6/E7 were determined to decrease gradually with the increase in EA incubation time and concentration
E7↓,
DNAdam↑, When DNA damage is introduced into cells from exogenous or endogenous sources there is an increase in the amount of intracellular reactive oxygen species (ROS)
ROS↑,
*BioAv↓, EA cannot be exploited for in vivo therapeutic applications in the current situation because of its poor water solubility and accordingly low bioavailability.
*BioEnh↑, As Lei [52] reported that EA in pomegranate leaf is rapidly absorbed and distributed as well as eliminated in rats
*Half-Life∅, blood concentration peaked at 0.5 h with Cmax = 7.29 μg/mL, and the drug concentration decreased to half of the original after 57 min of administration

1606- EA,    Ellagic acid inhibits proliferation and induced apoptosis via the Akt signaling pathway in HCT-15 colon adenocarcinoma cells
- in-vitro, Colon, HCT15
TumCP↓,
cycD1↓,
Apoptosis↑,
PI3K↓, strong inactivation of phosphatidylinositol 3-kinase (PI3K)/Akt pathway by EA
Akt↓,
ROS↑, production of reactive oxygen intermediates, which were examined by 2,7-dichlorodihydrofluorescein diacetate (H2DCF-DA), increased with time, after treatment with EA
Casp3↑, EA promoted the expression of Bax, caspase-3, and cytochrome c, and suppression of Bcl-2 activity in HCT-15 cells
Cyt‑c↑,
Bcl-2↓,
TumCCA↑, induces G2/M phase cell cycle arrest in HCT-15 cells
Dose∅, since 60 lM of the drug concentration could cause attentional loss of cells (60 and 45 % were viable in 12 and 24 h treatment, respectively) for crucial experiments, we used this dosage to assess the effect of EA in killing HCT-15 cells
ALP↓, significant decrease in the activity of ALP at 60 lM concentration of EA for the 12 h treatment
LDH↓, decrease in the activity of LDH in cells was proportional to increase in the incubation time with EA.
PCNA↓, EA down-regulated the expressions of PCNA and cyclin D1
P53↑, EA promoted p53 gene expression
Bax:Bcl2↑, increase in the Bcl-2/Bax ratio

1605- EA,    Ellagic Acid and Cancer Hallmarks: Insights from Experimental Evidence
- Review, Var, NA
*BioAv↓, Within the gastrointestinal tract, EA has restricted bioavailability, primarily due to its hydrophobic nature and very low water solubility.
antiOx↓, strong antioxidant properties [12,13], anti-inflammatory effects
Inflam↓,
TumCP↓, numerous studies indicate that EA possesses properties that can inhibit cell proliferation
TumCCA↑, achieved this by causing cell cycle arrest at the G1 phase
cycD1↓, reduction of cyclin D1 and E levels, as well as to the upregulation of p53 and p21 proteins
cycE↓,
P53↑,
P21↑,
COX2↓, notable reduction in the protein expression of COX-2 and NF-κB as a result of this treatment
NF-kB↓,
Akt↑, suppressing Akt and Notch signaling pathways
NOTCH↓,
CDK2↓,
CDK6↓,
JAK↓, suppression of the JAK/STAT3 pathway
STAT3↓,
EGFR↓, decreased expression of epidermal growth factor receptor (EGFR)
p‑ERK↓, downregulated the expression of phosphorylated ERK1/2, AKT, and STAT3
p‑Akt↓,
p‑STAT3↓,
TGF-β↓, downregulation of the TGF-β/Smad3
SMAD3↓,
CDK6↓, EA demonstrated the capacity to bind to CDK6 and effectively inhibit its activity
Wnt/(β-catenin)↓, ability of EA to inhibit phosphorylation of EGFR
Myc↓, Myc, cyclin D1, and survivin, exhibited decreased levels
survivin↓,
CDK8↓, diminished CDK8 level
PKCδ↓, EA has demonstrated a notable downregulatory impact on the expression of classical isoenzymes of the PKC family (PKCα, PKCβ, and PKCγ).
tumCV↓, EA decreased cell viability
RadioS↑, further intensified when EA was combined with gamma irradiation.
eff↑, EA additionally potentiated the impact of quercetin in promoting the phosphorylation of p53 at Ser 15 and increasing p21 protein levels in the human leukemia cell line (MOLT-4)
MDM2↓, finding points to the ability of reduced MDM2 levels
XIAP↓, downregulation of X-linked inhibitor of apoptosis protein (XIAP).
p‑RB1↓, EA exerted a decrease in phosphorylation of pRB
PTEN↑, EA enhances the protein phosphatase activity of PTEN in melanoma cells (B16F10)
p‑FAK↓, reduced phosphorylation of focal adhesion kinase (FAK)
Bax:Bcl2↑, EA significantly increases the Bax/Bcl-2 rati
Bcl-xL↓, downregulates Bcl-xL and Mcl-1
Mcl-1↓,
PUMA↑, EA also increases the expression of Bcl-2 inhibitory proapoptotic proteins PUMA and Noxa in prostate cancer cells
NOXA↑,
MMP↓, addition to the reduction in MMP, the release of cytochrome c into the cytosol occurs in pancreatic cancer cells
Cyt‑c↑,
ROS↑, induction of ROS production
Ca+2↝, changes in intracellular calcium concentration, leading to increased levels of EndoG, Smac/DIABLO, AIF, cytochrome c, and APAF1 in the cytosol
Endoglin↑,
Diablo↑,
AIF↑,
iNOS↓, decreased expression of Bcl-2, NF-кB, and iNOS were observed after exposure to EA at concentrations of 15 and 30 µg/mL
Casp9↑, increase in caspase 9 activity in EA-treated pancreatic cancer cells PANC-1
Casp3↑, EA-induced caspase 3 activation and PARP cleavage in a dose-dependent manner (10–100 µmol/L)
cl‑PARP↑,
RadioS↑, EA sensitizes and reduces the resistance of breast cancer MCF-7 cells to apoptosis induced by γ-radiation
Hif1a↓, EA reduced the expression of HIF-1α
HO-1↓, EA significantly reduced the levels of two isoforms of this enzyme, HO-1, and HO-2, and increased the levels of sEH (Soluble epoxide hydrolase) in LnCap
HO-2↓,
SIRT1↓, EA-induced apoptosis was associated with reduced expression of HuR and Sirt1
selectivity↑, A significant advantage of EA as a potential chemopreventive, anti-tumor, or adjuvant therapeutic agent in cancer treatment is its relative selectivity
Dose∅, EA significantly reduced the viability of cancer cells at a concentration of 10 µmol/L, while in healthy cells, this effect was observed only at a concentration of 200 µmol/L
NHE1↓, EA had the capacity to regulate cytosolic pH by downregulating the expression of the Na+/H+ exchanger (NHE1)
Glycolysis↓, led to intracellular acidification with subsequent impairment of glycolysis
GlucoseCon↓, associated with a decrease in the cellular uptake of glucose
lactateProd↓, notable reduction in lactate levels in supernatant
PDK1?, inhibit pyruvate dehydrogenase kinase (PDK) -bind and inhibit PDK3
PDK1?,
ECAR↝, EA has been shown to influence extracellular acidosis
COX1↓, downregulation of cancer-related genes, including COX1, COX2, snail, twist1, and c-Myc.
Snail↓,
Twist↓,
cMyc↓,
Telomerase↓, EA, might dose-dependently inhibit telomerase activity
angioG↓, EA may inhibit angiogenesis
MMP2↓, EA demonstrated a notable reduction in the secretion of matrix metalloproteinase (MMP)-2 and MMP-9.
MMP9↓,
VEGF↓, At lower concentrations (10 and 20 μM), EA led to a substantial increase in VEGF levels. However, at higher doses (40 and 100 μM), a notable reduction in VEGF
Dose↝, At lower concentrations (10 and 20 μM), EA led to a substantial increase in VEGF levels. However, at higher doses (40 and 100 μM), a notable reduction in VEGF
PD-L1↓, EA downregulated the expression of the immune checkpoint PD-L1 in tumor cells
eff↑, EA might potentially enhance the efficacy of anti-PD-L1 treatment
SIRT6↑, EA exhibited statistically significant upregulation of sirtuin 6 at the protein level in Caco2 cells
DNAdam↓, increase in DNA damage


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 11

Results for Effect on Cancer/Diseased Cells:
AIF↑,1,   Akt↓,4,   Akt↑,1,   p‑Akt↓,1,   ALP↓,1,   AMPK↑,1,   angioG↓,3,   AntiCan↑,1,   antiOx↓,1,   Apoptosis↑,3,   Bak↑,1,   BAX↑,5,   Bax:Bcl2↑,3,   Bcl-2↓,3,   Bcl-xL↓,2,   Ca+2↝,1,   Casp↑,1,   Casp3↑,4,   Casp9↑,1,   CDK2↓,2,   CDK2↑,1,   CDK4↓,1,   CDK6↓,4,   CDK8↓,1,   ChemoSen↑,2,   ChemoSideEff↓,1,   CHOP↑,1,   CIP2A↓,1,   cMyc↓,1,   COX1↓,1,   COX2↓,3,   cycD1↓,4,   cycE↓,1,   cycE1↓,1,   Cyt‑c↑,3,   Diablo↑,1,   DNAdam↓,1,   DNAdam↑,3,   Dose↝,1,   Dose∅,5,   DR4↑,1,   DR5↑,1,   E-cadherin↑,1,   E6↓,1,   E7↓,1,   ECAR↝,1,   eff↑,6,   EGFR↓,1,   EMT↓,1,   Endoglin↑,1,   ER Stress↑,1,   p‑ERK↓,1,   p‑FAK↓,1,   GlucoseCon↓,2,   GLUT1↓,1,   Glycolysis↓,2,   GSH↓,1,   GSTs↑,1,   Hif1a↓,3,   HO-1↓,2,   HO-2↓,1,   IGFBP7↑,1,   IL6↓,1,   Inflam↓,1,   iNOS↓,1,   JAK↓,1,   Ki-67↓,1,   lactateProd↓,1,   LC3II↑,1,   LDH↓,2,   MAD↓,1,   MAPK↓,1,   Mcl-1↓,1,   MDM2↓,1,   MMP↓,3,   MMP2↓,2,   MMP9↓,3,   mTOR↓,1,   mTOR⇅,1,   Myc↓,1,   NF-kB↓,2,   p‑NF-kB↓,1,   NHE1↓,3,   NOTCH↓,3,   NOXA↑,1,   OCR↓,1,   P21↑,4,   P53↑,5,   cl‑PARP↑,2,   PCNA↓,2,   PD-1↓,1,   PD-L1↓,1,   PDH↝,1,   PDK1?,2,   PDK1↓,1,   i-pH↓,1,   PI3K↓,2,   PKCδ↓,2,   PTEN↑,2,   PUMA↑,1,   RadioS↑,3,   p‑RB1↓,1,   ROS↓,1,   ROS↑,9,   selectivity↑,3,   SIRT1↓,2,   SIRT6↑,1,   SMAD3↓,1,   Snail↓,2,   STAT3↓,2,   p‑STAT3↓,2,   survivin↓,2,   TBARS↑,1,   Telomerase↓,1,   TGF-β↓,1,   TGF-β↑,1,   TNF-α↓,1,   TSC1↑,1,   TumAuto↑,1,   TumCCA↑,5,   TumCG↓,1,   TumCI↓,1,   TumCP↓,4,   tumCV↓,1,   TumMeta↓,1,   Twist↓,1,   VEGF↓,2,   VEGFR2↓,1,   Vim↓,1,   Wnt/(β-catenin)↓,2,   XIAP↓,2,   β-catenin/ZEB1↓,1,  
Total Targets: 132

Results for Effect on Normal Cells:
BioAv↓,4,   BioAv↑,1,   BioAv∅,1,   BioEnh↑,1,   Half-Life∅,1,   ROS∅,1,   toxicity∅,1,  
Total Targets: 7

Scientific Paper Hit Count for: ROS, Reactive Oxygen Species
11 Ellagic acid
1 Curcumin
1 Radiotherapy/Radiation
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:74  Target#:275  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

Home Page