Database Query Results : , , PPP

PPP, pentose phosphate pathway: Click to Expand ⟱
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The pentose phosphate pathway (PPP) is a metabolic pathway that generates NADPH and pentoses from glucose-6-phosphate. In cancer, the PPP is often upregulated to support the increased demand for NADPH, which is necessary for fatty acid synthesis, antioxidant defenses, and maintaining the balance of redox reactions.

High expression of PPP enzymes is often associated with poor prognosis in various cancers, including breast, lung, colorectal, prostate, pancreatic, and ovarian cancer.
Scientific Papers found: Click to Expand⟱
2327- 2DG,    2-Deoxy-d-Glucose and Its Analogs: From Diagnostic to Therapeutic Agents
- Review, Var, NA
Glycolysis↓, 2-DG inhibits glycolysis due to formation and intracellular accumulation of 2-deoxy-d-glucose-6-phosphate (2-DG6P), inhibiting the function of hexokinase and glucose-6-phosphate isomerase, and inducing cell death
HK2↓,
mt-ROS↑, 2-DG-mediated glucose deprivation stimulates reactive oxygen species (ROS) production in mitochondria, also leading to AMPK activation and autophagy stimulation.
AMPK↑,
PPP↓, 2-DG has been shown to block the pentose phosphate shunt
NADPH↓, Decreased levels of NADPH correlate with reduced glutathione levels, one of the major cellular antioxidants.
GSH↓,
Bax:Bcl2↑, Valera et al. also observed that in bladder cancer cells, 2-DG treatment modulates the Bcl-2/Bax protein ratio, driving apoptosis induction
Apoptosis↑,
RadioS↑, 2-DG radiosensitization results from its effect on thiol metabolism
eff↓, (NAC) treatment, downregulated glutamate cysteine ligase activity, or overexpression of ROS scavenging enzymes
Half-Life↓, its plasma half-life was only 48 min [117]) make 2-DG a rather poor drug candidate
other↝, Adverse effects of 2-DG administration in humans include fatigue, sweating, dizziness, and nausea, mimicking the symptoms of hypoglycemia
eff↓, Moreover, 2-DG has to be used at relatively high concentrations (≥5 mmol/L) in order to compete with blood glucose

5282- 3BP,  Rad,    3-Bromopyruvate-mediated MCT1-dependent metabolic perturbation sensitizes triple negative breast cancer cells to ionizing radiation
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, MDA-MB-468
Glycolysis↓, Metabolomic analyses showed that 3BP causes inhibition of glycolysis
RadioS↑, Overall, MCT1-mediated metabolic perturbation in combination with radiotherapy is shown to be a promising strategy for the treatment of glycolytic tumors such as TNBC, overcoming the selectivity challenges of targeting glycolysis with glucose analogs
eff↑, 3BP is selectively toxic to cells expressing MCT1
GAPDH↓, 3BP inhibits GAPDH but not hexokinase
PPP↑, Pentose phosphate pathway is upregulated in response to 3BP
GSH↓, Glutathione and NADH are depleted at early time points
ECAR↓, prolonged incubation with 20 μM 3BP for 24 h resulted in a statistically significant selective decrease in ECAR

206- Api,    Inhibition of glutamine utilization sensitizes lung cancer cells to apigenin-induced apoptosis resulting from metabolic and oxidative stress
- in-vitro, Lung, H1299 - in-vitro, Lung, H460 - in-vitro, Lung, A549 - in-vitro, CRC, HCT116 - in-vitro, Melanoma, A375 - in-vitro, Lung, H2030 - in-vitro, CRC, SW480
Glycolysis↓, glucose consumption, lactate production, and ATP production were all strongly decreased by apigenin
lactateProd↓,
PGK1↓,
ALDOA↓,
GLUT1↓, Apigenin reduces GLUT1 expression levels.
ENO1↓,
ATP↓,
Casp9↑,
Casp3↑,
cl‑PARP↑, cleavage
PI3K/Akt↓,
HK1↓, HK1, HK2
HK2↓,
ROS↑, Apigenin causes oxidative stress leading to apoptosis. Because apoptotic signal transduction cascades involving caspase-9, -3 and PARP cleavage can be activated by increased ROS levels
Apoptosis↑,
eff↓, Cancer cells expressing high levels of GLUT1 are resistant to apigenin-induced apoptosis through metabolic compensation of glucose utilization.
NADPH↓, apigenin significantly decreased glucose utilization through suppression of GLUT1 expression, and consequently decreased NADPH production, which led to increased ROS levels.
PPP↓, inhibition of the PPP

1963- GamB,    Gambogic acid exhibits promising anticancer activity by inhibiting the pentose phosphate pathway in lung cancer mouse model
- in-vitro, Lung, NA
ROS↑, anti-cancer activity of GA depended on reactive oxygen species (ROS)
6PGD↓, anticancer mechanism of GA, which involves the inhibition of 6PGD
PPP↓,

1964- GamB,    Gambogic acid suppresses the pentose phosphate pathway by covalently inhibiting 6PGD protein in cancer cells
- in-vitro, NA, NA
PPP↓, gambogic acid suppresses the pentose phosphate pathway (PPP) by covalently inhibiting the 6-phosphogluconate dehydrogenase (6PGD) protein.
6PGD↓,

2245- MF,    Quantum based effects of therapeutic nuclear magnetic resonance persistently reduce glycolysis
- in-vitro, Nor, NIH-3T3
Warburg↓, tNMR might have the potential to counteract the Warburg effect known from many cancer cells which are prone to glycolysis even under aerobic conditions.
Hif1a↓, combined treatment of tNMR and hypoxia (tNMR hypoxia) led to significantly altered HIF-1α protein levels, namely a further overall reduction in protein amounts
*Hif1a∅, Under normoxic conditions we did not find significant differences in Hif-1α mRNA and protein expression
Glycolysis↓, hypoxic tNMR treatment, driving cellular metabolism to a reduced glycolysis while mitochondrial respiration is kept constant even during reoxygenation.
*lactateProd↓, tNMR reduces lactate production and decreases cellular ADP levels under normoxic conditions
*ADP:ATP↓,
Pyruv↓, Intracellular pyruvate, which was as well decreased in hypoxic control cells, appeared to be further decreased after tNMR under hypoxia
ADP:ATP↓, tNMR under hypoxia further decreased the hypoxia induced decrease of the intracellular ADP/ATP ratio
*PPP↓, pentose phosphate pathway (PPP) is throttled after tNMR treatment, while cell proliferation is enhanced
*mt-ROS↑, tNMR under hypoxia increases mitochondrial and extracellular, but reduces cytosolic ROS
*ROS↓, but reduces cytosolic ROS
RPM↑, Because EMFs are known to affect ROS levels via the radical pair mechanism (RPM)
*ECAR↓, tNMR under normoxic conditions reduces the extracellular acidification rate (ECAR)

5156- PTL,    Rational Design of a Parthenolide-based Drug Regimen That Selectively Eradicates Acute Myelogenous Leukemia Stem Cells
- in-vitro, AML, NA
NADPH↑, parthenolide leads to induction of compensatory mechanisms that include up-regulated NADPH production via the pentose phosphate pathway
PPP↑, Metabolomic analyses reveal increased PPP activity for NADPH production in PTL-treated AML cells. compensatory mechanisms
NRF2↑, activation of the Nrf2-mediated oxidative stress response pathway. compensatory mechanisms
ROS↑,
CSCs↓, parthenolide, 2-deoxyglucose, temsirolimus (termed PDT) regimen is a potent means of targeting AML stem cells but has little to no effect on normal stem cells
selectivity↑,
other↝, combined with 2-deoxyglucose (D) and temsirolimus (T), drugs chosen for their ability to inhibit the PPP and the Nrf-2 mediated anti-oxidant response, respectively

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/CCNE↑, Resveratrol inhibited cell cycle progression by enhancing the levels of cyclin E and cyclin A
cycA1/CCNA1↑,
TumCCA↑,
cycD1/CCND1↑, 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.

3026- RosA,    Modulatory Effect of Rosmarinic Acid on H2O2-Induced Adaptive Glycolytic Response in Dermal Fibroblasts
- in-vitro, Nor, NA
*ROS↓, H2O2 caused a significant ROS increase in the cells, and pre-treatment with rosmarinic acid (5–50 µM) decreased ROS significantly in the presence of glutathione
*ATP↑, The rosmarinic acid also recovered intracellular ATP and decreased NADPH production via the pentose phosphate pathway.
*NADPH↓,
*HK2↓, (HK-2), phosphofructokinase-2 (PFK-2), and lactate dehydrogenase A (LDHA), were downregulated in cells treated with rosmarinic acid
*PFK2↓,
*LDHA↓,
*GSR↑, GSR), glutathione peroxidase-1 (GPx-1), and peroxiredoxin-1 (Prx-1) and redox protein thioredoxin-1 (Trx-1) were upregulated in treated cells compared to control cells.
*GPx↑,
*Prx↑,
*Trx↑,
*antiOx↑, To sum up, the rosmarinic acid could be used as an antioxidant against H2O2-induced adaptive responses in fibroblasts by modulating glucose metabolism, glycolytic genes, and GSH production.
*GSH↑, The pre-treatment of rosmarinic acid could raise intracellular GSH to protect cells from ROS
*ROS↓, rosmarinic acid pre-treatment reduced the amount of ROS in the fibroblasts upon the addition of H2O2
*GlucoseCon↓, both compounds also decreased glucose consumption and lactate production
*lactateProd↓,
*Glycolysis↝, The results indicated that rosmarinic acid is able to shape cellular glucose utilization, glycolysis, and GSH.
*ATP↑, The rosmarinic acid also recovered intracellular ATP and decreased NADPH production via the pentose phosphate pathway.
*NADPH↓,
*PPP↓,

1140- SIL,    Silibinin-mediated metabolic reprogramming attenuates pancreatic cancer-induced cachexia and tumor growth
- in-vitro, PC, AsPC-1 - in-vivo, PC, NA - in-vitro, PC, MIA PaCa-2 - in-vitro, PC, PANC1 - in-vitro, PC, Bxpc-3
TumCG↓,
Glycolysis↓,
cMyc↓,
STAT3↓,
TumCP↓,
Weight∅, prevents the loss of body weight and muscle.
Strength↑,
DNAdam↑,
Casp3↑,
Casp9↑,
GLUT1↓,
HK2↓,
LDHA↓,
GlucoseCon↓, silibinin inhibits glucose uptake and lactate release
lactateProd↓,
PPP↓, significant reduction in pentose phosphate pathway (PPP) metabolites, including 6-phosphogluconate (~50%), erythrose-4-phosphate (~40%), sedoheptulose-7-phosphate and sedoheptulose bis-phosphate (~ 70%)
Ki-67↓, reduced Ki67-positive cells
p‑STAT3↓,
cachexia↓,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 10

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

GSH↓, 2,   HK1↓, 1,   NRF2↑, 1,   OXPHOS↑, 1,   ROS↑, 3,   mt-ROS↑, 1,   RPM↑, 1,  

Mitochondria & Bioenergetics ⓘ

ADP:ATP↓, 1,   ATP↓, 1,   ATP↑, 1,   OCR↑, 1,  

Core Metabolism/Glycolysis ⓘ

6PGD↓, 2,   ALDOA↓, 1,   AMPK↑, 1,   cMyc↓, 1,   ECAR↓, 2,   ENO1↓, 1,   GAPDH↓, 1,   GlucoseCon↓, 1,   Glycolysis↓, 6,   HK2↓, 3,   lactateProd↓, 3,   LDHA↓, 1,   NADPH↓, 2,   NADPH↑, 1,   PDH↑, 1,   PGK1↓, 1,   PI3K/Akt↓, 1,   PPP↓, 6,   PPP↑, 2,   Pyruv↓, 1,   Warburg↓, 1,  

Cell Death ⓘ

Apoptosis↑, 2,   Bax:Bcl2↑, 1,   Casp3↑, 2,   Casp9↑, 2,  

Transcription & Epigenetics ⓘ

other↝, 2,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

cycA1/CCNA1↑, 1,   cycD1/CCND1↑, 1,   cycE/CCNE↑, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

CSCs↓, 1,   STAT3↓, 1,   p‑STAT3↓, 1,   TumCG↓, 2,  

Migration ⓘ

Ca+2↝, 1,   Ki-67↓, 1,   TumCP↓, 2,  

Angiogenesis & Vasculature ⓘ

Hif1a↓, 1,  

Barriers & Transport ⓘ

GLUT1↓, 2,  

Drug Metabolism & Resistance ⓘ

eff↓, 3,   eff↑, 1,   Half-Life↓, 1,   RadioS↑, 2,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

Ki-67↓, 1,  

Functional Outcomes ⓘ

cachexia↓, 1,   Strength↑, 1,   Weight∅, 1,  
Total Targets: 61

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   GPx↑, 1,   GSH↑, 1,   GSR↑, 1,   Prx↑, 1,   ROS↓, 3,   mt-ROS↑, 1,   Trx↑, 1,  

Mitochondria & Bioenergetics ⓘ

ADP:ATP↓, 1,   ATP↑, 2,  

Core Metabolism/Glycolysis ⓘ

ECAR↓, 1,   ECAR∅, 1,   GlucoseCon↓, 1,   Glycolysis↝, 1,   HK2↓, 1,   lactateProd↓, 2,   LDHA↓, 1,   NADPH↓, 2,   PFK2↓, 1,   PPP↓, 2,  

Transcription & Epigenetics ⓘ

other?, 1,  

Angiogenesis & Vasculature ⓘ

Hif1a∅, 1,  
Total Targets: 22

Scientific Paper Hit Count for: PPP, pentose phosphate pathway
2 Gambogic Acid
1 2-DeoxyGlucose
1 3-bromopyruvate
1 Radiotherapy/Radiation
1 Apigenin (mainly Parsley)
1 Magnetic Fields
1 Parthenolide
1 Resveratrol
1 Rosmarinic acid
1 Silymarin (Milk Thistle) silibinin
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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