PFK2 Cancer Research Results

PFK2, PFK2: Click to Expand ⟱
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“PFK-2” typically refers to the family of bifunctional enzymes (commonly known as 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases or PFKFBs) that regulate the levels of fructose-2,6-bisphosphate—a critical allosteric activator of glycolysis.

– PFK-2 enzymes catalyze the synthesis of fructose-2,6-bisphosphate (F2,6BP), which in turn is a potent activator of phosphofructokinase-1 (PFK-1), a key rate-limiting enzyme in glycolysis.
– Increased activity of PFK-2 contributes to enhanced glycolysis and the diversion of glycolytic intermediates into biosynthetic pathways that support rapid tumor cell growth and proliferation. – Upregulated glycolysis supports not only energy production but also the generation of precursors needed for nucleotide, amino acid, and lipid synthesis, aiding tumor progression.

– Elevated expression of certain PFK-2 isoforms (notably PFKFB3) has been observed in various cancers such as breast, colorectal, lung, and others.
– High PFK-2 expression is frequently associated with increased glycolytic activity, enhanced cell proliferation, and a shift toward an anabolic phenotype, correlating with more aggressive tumor behavior.
Scientific Papers found: Click to Expand⟱
2710- BBR,    Berberine inhibits the Warburg effect through TET3/miR-145/HK2 pathways in ovarian cancer cells
- in-vitro, Ovarian, SKOV3
Warburg↓, berberine inhibited the Warburg effect by up-regulating miR-145, miR-145 targeted HK2 directly.
miR-145↑,
HK2↓, westernblot suggested that berberine could significantly down regulate the expression of HK2
TET3↑, Berberine increased the expression of miR-145 by promoting the expression of TET3 and reducing the methylation level of the promoter region of miR-145 precursor gene.
Glycolysis↓, Furthermore, the effect of berberine on glycolysis related enzymes was detected, the results of qRT-PCR and westernblot suggested that berberine could significantly down regulate the expression of HK2
PKM2↓, Western blot results showed down-expression of miR-145 reversed berberine's inhibition of HK2 expression. PKM2, pyruvate kinase M2; HK2, Hexokinase2; GLUT1, glucose transporter 1; LDH, lactate dehydrogenase; PFK2, phosphofructokinase 2; PDK1,
GLUT1↓,
LDH↓,
PFK2↓,
PDK1↓,

1587- Citrate,    ATP citrate lyase: A central metabolic enzyme in cancer
- Review, NA, NA
ACLY↓, administration of citrate at high level mimics a strong inhibition of ACLY and could be tested to strengthen the effects of current therapies. -a strong ACLY inhibition could be mimicked by by flooding the cytosol with citrate.
other↓, ACLY inhibition by simple drugs such as HCA or bempedoic acid should be tested, optimally associated with glycolytic inhibitors (or glucose starvation diet) and current therapies.
PFK1↓, citrate promotes: - the inactivation of PFK1 and decreases ATP production [
ATP↓,
PFK2↓, inhibition of PFK2 in ascite cancer cells
Mcl-1↓, deactivation of the anti-apoptotic factor Mcl-1 and the activation of caspases such as caspase 2, 3 and 9
Casp3↑,
Casp2↑,
Casp9↑,
IGF-1R↓, downregulation of the IGF-1R/PI3K/AKT
PI3K↓,
Akt↓,
p‑Akt↓, decreased phosphorylation of AKT and ERK in non-small cell lung cancer
p‑ERK↓,
PTEN↑, activation of PTEN suppressor,
Snail↓, reversion of dedifferentiation (in particular through Snail inhibition with E-cadherin expression) and stimulation of T lymphocytes response
E-cadherin↑,
ChemoSen↑, increasing the sensitivity of tumors to cisplatin

1578- Citrate,    Understanding the Central Role of Citrate in the Metabolism of Cancer Cells and Tumors: An Update
- Review, Var, NA
TCA↑,
FASN↑, Cytosolic acetyl-CoA sustains fatty acid (FA) synthesis (FAS)
Glycolysis↓,
glucoNG↑, while it enhances gluconeogenesis by promoting fructose-1,6-biphosphatase (FBPase)
PFK1↓, citrate directly inhibits the main regulators of glycolysis, phosphofructokinase-1 (PFK1) and phosphofructokinase-2 (PFK2)
PFK2↓, well-known inhibitor of PFK
FBPase↑, enhances gluconeogenesis by promoting fructose-1,6-biphosphatase (FBPase)
TumCP↓, inhibits the proliferation of various cancer cells of solid tumors (human mesothelioma, gastric and ovarian cancer cells) at high concentrations (10–20 mM),
eff↑, promoting apoptosis and the sensitization of cells to cisplatin
ACLY↓, higher concentrations (10 mM or more) decreased both acetylation and ACLY expression
Dose↑, In various cell lines, a high concentration of citrate—generally above 10 mM—inhibits the proliferation of cancer cells in a dose dependent manner
Casp3↑,
Casp2↑,
Casp8↑,
Casp9↑,
Bcl-xL↓,
Mcl-1↓,
IGF-1R↓, citrate at high concentration (10 mM) also inhibits the insulin-like growth factor-1 receptor (IGF-1R)
PI3K↓, pathways
Akt↓, activates PTEN, the key phosphatase inhibiting the PI3K/Akt pathway
mTOR↓,
PTEN↑, high dose of citrate activates PTEN
ChemoSen↑, citrate increases the sensibility of cells to chemotherapy (in particular, cisplatin)
Dose?, oral gavage of citrate sodium (4 g/kg twice a day) for several weeks (4 to 7 weeks) significantly regressed tumors

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↓,

2419- SK,    Regulation of glycolysis and the Warburg effect in wound healing
- in-vivo, Nor, NA
Glycolysis↓, Treatment with 5–10 μM of the glycolysis inhibitor shikonin significantly decreased gene expression of the facilitative glucose transporters, GLUT1 and GLUT3
GLUT1↓,
GLUT3↓,
HK2↓, shikonin downregulated expression of the rate-limiting enzymes HK1 and HK2, although a 20 μM dose was needed
HK1↓, HK1
PFK1↓, Shikonin treatment also downregulated the rate-limiting enzyme PFK1
PFK2↓, PFK2 expression was only significantly lowered with a 20 μM dose
PKM2↓, 5 μM shikonin treatment inhibits gene expression of PKM2 (8.59 vs. 2.30, P < 0.001) and downregulated PDK1
lactateProd↓, coupled with decreased lactate production at higher concentrations of shikonin (10 μM and 20 μM)
GlucoseCon↓, shikonin effectively downregulated key enzymes involved in glucose uptake, glycolysis, and lactate production


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 ⓘ

HK1↓, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 1,  

Core Metabolism/Glycolysis ⓘ

ACLY↓, 2,   FASN↑, 1,   FBPase↑, 1,   glucoNG↑, 1,   GlucoseCon↓, 1,   Glycolysis↓, 3,   HK2↓, 2,   lactateProd↓, 1,   LDH↓, 1,   PDK1↓, 1,   PFK1↓, 3,   PFK2↓, 4,   PKM2↓, 2,   TCA↑, 1,   Warburg↓, 1,  

Cell Death ⓘ

Akt↓, 2,   p‑Akt↓, 1,   Bcl-xL↓, 1,   Casp2↑, 2,   Casp3↑, 2,   Casp8↑, 1,   Casp9↑, 2,   Mcl-1↓, 2,  

Transcription & Epigenetics ⓘ

miR-145↑, 1,   other↓, 1,   TET3↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

p‑ERK↓, 1,   IGF-1R↓, 2,   mTOR↓, 1,   PI3K↓, 2,   PTEN↑, 2,  

Migration ⓘ

E-cadherin↑, 1,   Snail↓, 1,   TumCP↓, 1,  

Barriers & Transport ⓘ

GLUT1↓, 2,   GLUT3↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 2,   Dose?, 1,   Dose↑, 1,   eff↑, 1,  

Clinical Biomarkers ⓘ

LDH↓, 1,  
Total Targets: 43

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   GPx↑, 1,   GSH↑, 1,   GSR↑, 1,   Prx↑, 1,   ROS↓, 2,   Trx↑, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↑, 2,  

Core Metabolism/Glycolysis ⓘ

GlucoseCon↓, 1,   Glycolysis↝, 1,   HK2↓, 1,   lactateProd↓, 1,   LDHA↓, 1,   NADPH↓, 2,   PFK2↓, 1,   PPP↓, 1,  
Total Targets: 16

Scientific Paper Hit Count for: PFK2, PFK2
2 Citric Acid
1 Berberine
1 Rosmarinic acid
1 Shikonin
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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