NHE1 Cancer Research Results
NHE1, Na+/H+ exchanger isoform 1: Click to Expand ⟱
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Plays a crucial role in cancer cell proliferation and metastasis.
NHE1 is a ubiquitously expressed acid-extruding membrane transport protein, and upregulation of its expression and/or activity is commonly correlated with tumor malignancy.
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Scientific Papers found: Click to Expand⟱
*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/CCND1↓, reduction of cyclin D1 and E levels, as well as to the upregulation of p53 and p21 proteins
cycE/CCNE↓,
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
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
Apoptosis↑,
Bcl-2↓,
P53↑, up-regulated expression of p53,
cl‑Casp3↑,
Cyt‑c↑,
ROS↑, induced ROS production by suppressing the expression of antioxidant regulatory enzymes, namely superoxide dismutase and catalase
SOD↓,
Catalase↓,
Glycolysis↓,
GLUT3↓,
LDHA↓, LDHA inhibitor
MCT1↓,
NHE1↓,
ATPase↓,
CAIX↓,
aSmase↝, Figure 3b shows that quercetin treatment caused a dose-dependent augmentation in mRNA levels of Diablo and FAS
Diablo↑,
Fas↓,
Hsc70↓, coupled with a dose-responsive reduction in transcriptional activity of HSC70, HIF1A, Mcl-1, Hsp90 and BIRC4.
Hif1a↓,
Mcl-1↓,
HSP90↓,
FLT4↓, A dose-dependent drop in mRNA levels of FLT4, EPHB4, DNAPK, PARP1, ATM, perlecan, GnTV and heparanase genes was observed after treatment of PC-3
cells with quercetin
EphB4↓,
DNA-PK↓,
PARP1↓,
ATM↓,
XIAP↝,
PLC↓,
GnT-V↝,
heparanase↝,
NM23↑, quercetin significantly exerted a dose-responsive rise in transcriptional levels of NM23 and CSR1 genes
CSR1↑,
SPP1↓, coupled with an expressive lowering in mRNA levels of SPP1, DNMT1, HDAC4, CXCR4, b-catenin and NHE1.
DNMT1↓,
HDAC4↓,
CXCR4↓,
β-catenin/ZEB1↓,
FBXW7↝,
AMACR↓,
cycD1/CCND1↓,
IGF-1R↓, down-regulation of mRNA levels of AMACR, cyclin D1, NOS2A, IGF1R, IMPDH1, IMPDH2 and HEC1
IMPDH1↓,
IMPDH2↓,
HEC1↓,
NHE1↓,
NOS2↓,
hepatoP↑, This group of flavonoids has been extensively studied and they have been used as hepato-protective substances
AntiCan↑, however, silymarin compounds have clear anticancer effects
TumCMig↓, decreasing migration through multiple targeting, decreasing hypoxia inducible factor-1α expression, i
Hif1a↓, In prostate cancer cells silibinin inhibited HIF-1α translation
selectivity↑, antitumoral activity of silymarin compounds is limited to malignant cells while the nonmalignant cells seem not to be affected
toxicity∅, long history of silymarin use in human diseases without toxicity after prolonged administration.
*antiOx↑, as an antioxidant, by scavenging prooxidant free radicals
*Inflam↓, antiinflammatory effects similar to those of indomethacin,
TumCCA↑, MDA-MB 486 breast cancer cells, G1 arrest was found due to increased p21 and decreased CDKs activity
P21↑,
CDK4↓,
NF-kB↓, human prostate carcinoma cells, silymarin decreased ligand binding to Erb1 135 and NF-kB expression was strongly inhibited by silymarin in hepatoma cell
ERK↓, human prostate carcinoma cells, silymarin decreased ligand binding to Erb1 135 and NF-kB expression was strongly inhibited by silymarin in hepatoma cell
PSA↓, Treating prostate carcinoma cells with silymarin the levels of PSA were significantly decreased and cell growth was inhibited through decreased CDK activity and induction of Cip1/p21 and Kip1/p27. 1
TumCG↓,
p27↑,
COX2↓, such as anti-COX2 and anti-IL-1α activity, 140 antiangiogenic effects through inhibition of VEGF secretion, upregulation of Insulin like Growth Factor Binding Protein 3 (IGFBP3), 141 and inhibition of androgen receptors.
IL1↓,
VEGF↓,
IGFBP3↑,
AR↓,
STAT3↓, downregulation of the STAT3 pathway which was seen in many cell models.
Telomerase↓, silymarin has the ability to decrease telomerase activity in prostate cancer cells
Cyt‑c↑, mitochondrial cytochrome C release-caspase activation.
Casp↑,
eff↝, Malignant p53 negative cells show only minimal apoptosis when treated with silymarin. Therefore, one conclusion is that silymarin may be useful in tumors with conserved p53.
HDAC↓, inhibit histone deacetylase activity;
HATs↑, increase histone acetyltransferase activity
Zeb1↓, reduce expression of the transcription factor ZEB1
E-cadherin↑, increase expression of E-cadherin;
miR-203↑, increase expression of miR-203
NHE1↓, reduce activation of sodium hydrogen isoform 1 exchanger (NHE1)
MMP2↓, target β catenin and reduce the levels of MMP2 and MMP9
MMP9↓,
PGE2↓, reduce activation of prostaglandin E2
Vim↓, suppress vimentin expression
Wnt↓, inhibit Wnt signaling
angioG↓, Silymarin inhibits angiogenesis.
VEGF↓, VEGF downregulation
*TIMP1↓, Silymarin has the capacity to decrease TIMP1 expression166–168 in mice.
EMT↓, found that silibinin had no effect on EMT. However, the opposite was found in other malignant tissues160–162 where it showed inhibitory effects.
TGF-β↓, Silibinin reduces the expression of TGF β2 in different tumors such as triple negative breast, 174 prostate, and colorectal cancers.
CD44↓, Silibinin decreased CD44 expression and the activation of EGFR (epidermal growth factor receptor)
EGFR↓,
PDGF↓, silibinin had the ability to downregulate PDFG in fibroblasts, thus decreasing proliferation.
*IL8↓, Flavonoids, in general, reduce levels of IL-8. Curcumin, 200 apigenin, 201 and silybin showed the ability to decrease IL-8 levels
SREBP1↓, Silymarin inhibited STAT3 phosphorylation and decreased the expression of intranuclear sterol regulatory element binding protein 1 (SREBP1), decreasing lipid synthesis.
MMP↓, reduced membrane potential and ATP content
ATP↓,
uPA↓, silibinin decreased MMP2, MMP9, and urokinase plasminogen activator receptor level (uPAR) in neuroblastoma cells. uPAR is also a marker of cell invasion.
PD-L1↓, Silibinin inhibits PD-L1 by impeding STAT5 binding in NSCLC.
NOTCH↓, Silybin inhibited Notch signaling in hepatocellular carcinoma cells showing antitumoral effects
*SIRT1↑, Silymarin can also increase SIRT1 expression in other tissues, such as hippocampus, 221 articular chondrocytes, 222 and heart muscle
SIRT1↓, Silymarin seems to act differently in tumors: in lung cancer cells SIRT downregulated SIRT1 and exerted multiple antitumor effects such as reduced adhesion and migration and increased apoptosis.
CA↓, Silymarin has the ability to inhibit CA isoforms CA I and CA II.
Ca+2↑, ilymarin increases mitochondrial release of Ca++ and lowers mitochondrial membrane potential in cancer cell
chemoP↑, Silymarin: Decreasing Side Effects and Toxicity of Chemotherapeutic Drugs
cardioP↑, There is also evidence that it protects the heart from doxorubicin toxicity, however, it is less potent than quercetin in this effect.
Dose↝, oral administration of 240 mg of silybin to 6 healthy volunteers the following results were obtained 377 : maximum\,plasmaconcentration0.34±0.16𝜇g/mL
Half-Life↝, and time to maximum plasma concentration 1.32 ± 0.45 h. Absorption half life 0.17 ± 0.09 h, elimination half life 6.32 ± 3.94 h
BioAv↓, silymarin is not soluble in water and oral administration shows poor absorption in the alimentary tract (approximately 1% in rats,
BioAv↓, Our conclusion is that, from a bioavailability standpoint, it is much easier to achieve migration inhibition, than proliferative reduction.
BioAv↓, Combination with succinate: is available on the market under the trade mark Legalon® (bis hemisuccinate silybin). Combination with phosphatidylcholine:
toxicity↝, 13 g daily per os divided into 3 doses was well tolerated. The most frequent adverse event was asymptomatic liver toxicity.
Half-Life↓, It may be necessary to administer 800 mg 4 times a day because the half-life is short.
ROS↓, its ability as an antioxidant reduces ROS production
FAK↓, Silibinin decreased human osteosarcoma cell invasion through Erk inhibition of a FAK/ERK/uPA/MMP2 pathway
Showing Research Papers: 1 to 5 of 5
* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 5
Pathway results for Effect on Cancer / Diseased Cells:
Redox & Oxidative Stress ⓘ
antiOx↓, 1, Catalase↓, 1, HO-1↓, 1, HO-2↓, 1, ROS↓, 2, ROS↑, 2, SOD↓, 1,
Mitochondria & Bioenergetics ⓘ
AIF↑, 1, ATP↓, 1, MMP↓, 2, XIAP↓, 1, XIAP↝, 1,
Core Metabolism/Glycolysis ⓘ
AMACR↓, 1, CAIX↓, 1, cMyc↓, 1, ECAR↝, 1, GlucoseCon↓, 2, Glycolysis↓, 3, lactateProd↓, 1, LDHA↓, 1, PDK1?, 2, SIRT1↓, 2, SREBP1↓, 1,
Cell Death ⓘ
Akt↑, 1, p‑Akt↓, 1, Apoptosis↑, 1, aSmase↝, 1, Bax:Bcl2↑, 1, Bcl-2↓, 1, Bcl-xL↓, 1, Casp↑, 1, Casp3↑, 1, cl‑Casp3↑, 1, Casp9↑, 1, CSR1↑, 1, Cyt‑c↑, 3, Diablo↑, 2, Fas↓, 1, iNOS↓, 1, Mcl-1↓, 2, MCT1↓, 1, MDM2↓, 1, Myc↓, 1, NOXA↑, 1, p27↑, 1, PUMA↑, 1, survivin↓, 1, Telomerase↓, 2,
Transcription & Epigenetics ⓘ
HATs↑, 1, SPP1↓, 1, tumCV↓, 1,
Protein Folding & ER Stress ⓘ
Hsc70↓, 1, HSP90↓, 1,
DNA Damage & Repair ⓘ
ATM↓, 1, DNA-PK↓, 1, DNAdam↓, 1, DNMT1↓, 1, P53↑, 2, cl‑PARP↑, 1, PARP1↓, 1, SIRT6↑, 1,
Cell Cycle & Senescence ⓘ
CDK2↓, 1, CDK4↓, 1, cycD1/CCND1↓, 2, cycE/CCNE↓, 1, P21↑, 2, p‑RB1↓, 1, TumCCA↑, 2,
Proliferation, Differentiation & Cell State ⓘ
CD44↓, 1, CDK8↓, 1, EMT↓, 1, ERK↓, 1, p‑ERK↓, 1, FBXW7↝, 1, HDAC↓, 1, HDAC4↓, 1, IGF-1R↓, 1, IGFBP3↑, 1, NOTCH↓, 2, PTEN↑, 1, STAT3↓, 2, p‑STAT3↓, 1, TumCG↓, 1, Wnt↓, 1, Wnt/(β-catenin)↓, 1,
Migration ⓘ
ATPase↓, 1, CA↓, 1, Ca+2↑, 1, Ca+2↝, 1, E-cadherin↑, 1, EphB4↓, 1, FAK↓, 1, p‑FAK↓, 1, GnT-V↝, 1, heparanase↝, 1, miR-203↑, 1, MMP2↓, 2, MMP9↓, 2, NM23↑, 1, PDGF↓, 1, PKCδ↓, 1, SMAD3↓, 1, Snail↓, 1, TGF-β↓, 2, TumCMig↓, 1, TumCP↓, 1, Twist↓, 1, uPA↓, 1, Vim↓, 1, Zeb1↓, 1, β-catenin/ZEB1↓, 1,
Angiogenesis & Vasculature ⓘ
angioG↓, 2, EGFR↓, 2, Endoglin↑, 1, FLT4↓, 1, Hif1a↓, 3, VEGF↓, 3,
Barriers & Transport ⓘ
GLUT3↓, 1, NHE1↓, 6,
Immune & Inflammatory Signaling ⓘ
COX1↓, 1, COX2↓, 2, CXCR4↓, 1, IL1↓, 1, Inflam↓, 1, JAK↓, 1, NF-kB↓, 2, PD-L1↓, 2, PGE2↓, 1, PSA↓, 1,
Cellular Microenvironment ⓘ
i-pH↓, 1, PLC↓, 1,
Hormonal & Nuclear Receptors ⓘ
AR↓, 1, CDK6↓, 2,
Drug Metabolism & Resistance ⓘ
BioAv↓, 3, Dose↝, 2, Dose∅, 1, eff↑, 2, eff↝, 1, Half-Life↓, 1, Half-Life↝, 1, RadioS↑, 2, selectivity↑, 2,
Clinical Biomarkers ⓘ
AR↓, 1, EGFR↓, 2, HEC1↓, 1, Myc↓, 1, NOS2↓, 1, PD-L1↓, 2, PSA↓, 1,
Functional Outcomes ⓘ
AntiCan↑, 1, cardioP↑, 1, chemoP↑, 1, hepatoP↑, 1, IMPDH1↓, 1, IMPDH2↓, 1, toxicity↝, 1, toxicity∅, 1,
Total Targets: 157
Pathway results for Effect on Normal Cells:
Redox & Oxidative Stress ⓘ
antiOx↑, 1,
Core Metabolism/Glycolysis ⓘ
SIRT1↑, 1,
Migration ⓘ
TIMP1↓, 1,
Immune & Inflammatory Signaling ⓘ
IL8↓, 1, Inflam↓, 1,
Drug Metabolism & Resistance ⓘ
BioAv↓, 1,
Total Targets: 6
Scientific Paper Hit Count for: NHE1, Na+/H+ exchanger isoform 1
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
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