condition found tbRes List
PFK1, Phosphofructokinase-1: Click to Expand ⟱
Source:
Type:
Phosphofructokinase-1 (PFK1) is a key regulatory enzyme in glycolysis that catalyzes the conversion of fructose-6-phosphate to fructose-1,6-bisphosphate.
– As a rate-limiting enzyme in glycolysis, PFK1 is subject to complex regulation through allosteric effectors including ATP, AMP, and fructose-2,6-bisphosphate.
• Metabolic Control:
–PFK1 activity is central to controlling the pace of glycolysis, thereby influencing energy production and intermediary metabolite supply.
– In highly proliferative cells or cells under growth conditions, increased glycolytic flux (and, by extension, PFK1 activity) supports the biosynthetic demands of cell division.

– Many tumors (including breast, colorectal, and lung cancers) have been reported to have increased PFK1 expression/activity relative to normal tissues.
– High glycolytic flux, driven partly by enhanced PFK1, supports rapid cell proliferation and survival in the nutrient/stress-challenged tumor microenvironment.

Inhibitors:(typically glycolysis is targeted more broadly)
-Citrate
-Hydrogen ions (pH) – Acidic conditions can have inhibitory effects.
-3PO: inhibits PFKFB3, thereby indirectly reducing PFK1 activity.
-Resveratrol can downregulate glycolytic flux in cancer cells, which may indirectly affect PFK1 activity.
- FMDs offer an indirect strategy to modulate cancer metabolism by broadly reducing glycolysis. Their impact on PFK1 is likely part of a complex network of metabolic adaptations rather than a direct inhibitory effect.
Scientific Papers found: Click to Expand⟱
2291- Ba,  BA,    Baicalein and Baicalin Promote Melanoma Apoptosis and Senescence via Metabolic Inhibition
- in-vitro, Melanoma, SK-MEL-28 - in-vitro, Melanoma, A375
LDHA↓, both baicalein and baicalin inhibited LDHα expression in Mel586, A375, and B16F0 melanoma cells, and ENO1 expression in SK-MEL-2 and A375 cells, as well as partially suppressed PKM2 expression in SK-MEL-2, A375, and B16F0 tumor cells
ENO1↓,
PKM2↓,
GLUT1↓, Baicalein and baicalin treatments markedly suppressed gene expression of Glut1, Glut3, HK2, TPI, GPI, and PFK1 in both human and mouse melanoma cells
GLUT3↓,
HK2↓,
PFK1↓,
GPI↓,
TPI↓,
GlucoseCon↓, baicalein and baicalin significantly inhibited glucose uptake abilities of four melanoma cell lines no matter of N-RAS and B-RAF mutation statuses
TumCG↓, baicalein and baicalin strongly suppressed tumor growth and proliferation of both human and mouse melanoma cells
TumCP↓,
mTORC1↓, Down-Regulation of mTORC1-HIF1α Signaling in Melanoma Cells Is Responsible for Glucose Metabolism Inhibition Induced by Baicalein and Baicalin
Hif1a↓,
Ki-67↓, We observed that baicalein and baicalin treatments markedly suppressed tumor cell proliferation as indicated by a decrease of Ki-67+ cell populations in tumor tissues

2293- Ba,    Baicalein suppresses inflammation and attenuates acute lung injury by inhibiting glycolysis via HIF‑1α signaling
- in-vitro, Nor, MH-S - in-vivo, NA, NA
*Hif1a↓, baicalein could inhibit HIF‑1α signaling, thus suppressing glycolysis, and improving inflammatory responses
*Glycolysis↓, Baicalein inhibits glycolysis in LPS-induced macrophages and in the lung tissues of mice with LPS-induced ALI
*Inflam↓, Baicalein inhibits the inflammatory response in LPS-induced macrophages and mice with LPS-induced ALI
*HK2↓, baicalein could inhibit the expression of key glycolysis-related enzymes (HK2, PFK1 and PKM2) in the lungs of mice with LPS-induced ALI and in LPS-induced macrophages
*PFK1↓,
*PKM2↓,

2740- BetA,    Effects and mechanisms of fatty acid metabolism-mediated glycolysis regulated by betulinic acid-loaded nanoliposomes in colorectal cancer
- in-vitro, CRC, HCT116
TumCP↓, BA-NLs significantly suppressed the proliferation and glucose uptake of CRC cells by regulating potential glycolysis and fatty acid metabolism targets and pathways, which forms the basis of the anti-CRC function of BA-NLs.
Glycolysis↓,
HK2↓, HK2, PFK-1, PEP and PK isoenzyme M2 (PKM2) in glycolysis, and of ACSL1, CPT1a and PEP in fatty acid metabolism, were blocked by BA-NLs, which play key roles in the inhibition of glycolysis and fatty acid-mediated production of pyruvate and lactate.
PFK1↓,
PKM2↓,
ACSL1↓,
CPT1A↓,
FASN↓,
FAO↓, Significant reduction of FAO was detected in BA-NL-treated HCT116 cells
GlucoseCon↓, glucose uptake in HCT116 cells was significantly decreased by BA-NLs
lactateProd↓, lactic acid secretion was significantly suppressed in HCT116 cells treated with BA-NLs

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

1583- Citrate,    Extracellular citrate and metabolic adaptations of cancer cells
- Review, NA, NA
Warburg↓, hypothesis that extracellular citrate might play a major role in cancer metabolism and is responsible for a switch between Warburg effect and OXPHOS
OXPHOS↓,
Dose∅, 10 mM citrate, cancer cells were shown to have decreased proliferation, ATP synthesis,
TumCP↓,
ATP↓,
eff↑, increased apoptosis and sensitivity to cis-platin
Apoptosis↑,
TumCG↓, high doses of citrate in vivo decreased tumour growth
PFK1↓, increased levels of cytosolic citrate taken up from the extracellular space would decrease phosphofructokinase-1 (PFK-1) activity
NA↓,

2308- CUR,    Counteracting Action of Curcumin on High Glucose-Induced Chemoresistance in Hepatic Carcinoma Cells
- in-vitro, Liver, HepG2
GlucoseCon↓, Curcumin obviated the hyperglycemia-induced modulations like elevated glucose consumption, lactate production, and extracellular acidification, and diminished nitric oxide and reactive oxygen species (ROS) production
lactateProd↓,
ECAR↓,
NO↓,
ROS↑, Curcumin favors the ROS production in HepG2 cells in normal as well as hyperglycemic conditions. ROS production was detected in cancer cells treated with curcumin, or doxorubicin, or their combinations in NG or HG medium for 24 h
HK2↓, HKII, PFK1, GAPDH, PKM2, LDH-A, IDH3A, and FASN. Metabolite transporters and receptors (GLUT-1, MCT-1, MCT-4, and HCAR-1) were also found upregulated in high glucose exposed HepG2 cells. Curcumin inhibited the elevated expression of these enzymes, tr
PFK1↓,
GAPDH↓,
PKM2↓,
LDHA↓,
FASN↓,
GLUT1↓, Curcumin treatment was able to significantly decrease the expression of GLUT1, HKII, and HIF-1α in HepG2 cells either incubated in NG or HG medium.
MCT1↓,
MCT4↓,
HCAR1↓,
SDH↑, Curcumin also uplifted the SDH expression, which was inhibited in high glucose condition
ChemoSen↑, Curcumin Prevents High Glucose-Induced Chemoresistance
ROS↑, Treatment of cells with doxorubicin in presence of curcumin was found to cooperatively augment the ROS level in cells of both NG and HG groups.
BioAv↑, Curcumin Favors Drug Accumulation in Cancer Cells
P53↑, An increased expression of p53 in curcumin-treated cells can be suggestive of susceptibility towards cytotoxic action of anticancer drugs
NF-kB↓, curcumin has therapeutic benefits in hyperglycemia-associated pathological manifestations and through NF-κB inhibition
pH↑, Curcumin treatment was found to resist the lowering of pH of culture supernatant both in NG as well in HG medium.

1861- dietFMD,  Chemo,    Fasting induces anti-Warburg effect that increases respiration but reduces ATP-synthesis to promote apoptosis in colon cancer models
- in-vitro, Colon, CT26 - in-vivo, NA, NA
selectivity↑, Short-term-starvation (STS) was shown to protect normal cells and organs but to sensitize different cancer cell types to chemotherapy
ChemoSen↑, STS potentiated the effects of OXP on the suppression of colon carcinoma growth and glucose uptake in both in vitro and in vivo models.
BG↓, glucose and amino acid deficiency conditions imposed by STS promote an anti-Warburg effect
AminoA↓,
Warburg↓,
OCR↑, characterized by increased oxygen consumption but failure to generate ATP, resulting in oxidative damage and apoptosis.
ATP↓,
ROS↑, a significant increase in O2consumption rate (OCR), indicative of an increased oxidative metabolism, was observed
Apoptosis↑,
GlucoseCon↓, STS was as effective as oxaliplatin (OXP) in reducing the average tumor glucose consumption
PI3K↓, STS and in particular STS+OXP down-regulated the expression of PI3K
PTEN↑, and up-regulated PTEN expression
GLUT1↓, STS induced a profound reduction in GLUT1 , GLUT2 , HKII , PFK1, PK
GLUT2↓,
HK2↓,
PFK1↓,
PKA↓,
ATP:AMP↓, Accordingly, the ATP/AMP ratio, a good indicator of cellular energy charge, was dramatically reduced by the two STS settings
Glycolysis↓, results strongly support the effect of STS on reducing glycolysis and lactate production and increasing respiration at Complexes I-IV resulting in superoxide production/oxidative stress but in reduced ATP generation.
lactateProd↓,

1070- IVM,    Ivermectin accelerates autophagic death of glioma cells by inhibiting glycolysis through blocking GLUT4 mediated JAK/STAT signaling pathway activation
- vitro+vivo, GBM, NA
TumCG↓,
LC3II↑,
p62↓,
ATP↓,
Pyruv↓,
GlucoseCon↑, promoted glucose uptake
HK2↓,
PFK1↓,
GLUT4↓,
Glycolysis↓,
JAK2↓,
p‑STAT3↓,
p‑STAT5↓,

2421- PB,    Sodium butyrate inhibits aerobic glycolysis of hepatocellular carcinoma cells via the c‐myc/hexokinase 2 pathway
- in-vitro, HCC, HCCLM3 - in-vivo, NA, NA - in-vitro, HCC, Bel-7402 - in-vitro, HCC, SMMC-7721 cell - in-vitro, Nor, L02
Glycolysis↓, NaBu inhibited aerobic glycolysis in the HCC cells in vivo and in vitro
Apoptosis↑, NaBu induced apoptosis while inhibiting the proliferation of the HCC cells in vivo and in vitro.
TumCP↓,
lactateProd↓, the compound inhibited the release of lactate and glucose consumption in the HCC cells in vitro and inhibited the production of lactate in vivo.
GlucoseCon↓,
HK2↓, NaBu downregulated HK2 expression via c‐myc signalling.
ChemoSen↑, upregulation of glycolysis in the HCC cells induced by sorafenib was impeded by NaBu, thereby enhancing the anti‐HCC effect of sorafenib in vitro and in vivo.
*toxicity↓, Moreover, NaBu did not affect the mouse serum levels of ALT, AST or creatinine (Figure S2A). Furthermore, no obvious pathological changes were observed in the liver, lung, heart or kidney sections of the NaBu‐treated mice
cMyc↓, mRNA expression of c‐myc was significantly inhibited in both HCC‐LM3 and Bel‐7402 cell lines upon treatment with 3 mM NaBu for 48 h
PFK1↓, Western blotting showed that NaBu treatment for 48 h suppressed the expressions of HK2, PFK1 and LDH-A inthe HCC-LM3 and Bel- 6402 cell lines in a dose- dependent manner
LDHA↓,
cMyc↓, NaBu inhibited the expression of c-myc in the total and nuclear lysate in a dose-depedent manner. NaBu suppressed the expression of c- myc in the tumour tissue
ChemoSen↑, NaBu impairs the enhancement of aerobic glycolysis in the HCC cells by sorafenib and improves the effect of the drug on HCC cells both in vitro and in vivo.

2380- PBG,    Potential Strategies for Overcoming Drug Resistance Pathways Using Propolis and Its Polyphenolic/Flavonoid Compounds in Combination with Chemotherapy and Radiotherapy
- Review, Var, NA
Hif1a↓, Flavonoid components from propolis, as inhibitors of HIF-1, have the ability to regulate critical glycolytic components in cancer cells, including (PKM2), (LDHA), (GLUTs), (HKII), (PFK-1), and (PDK)
Glycolysis↓,
PKM2↓,
LDHA↓,
GLUT2↓,
HK2↓,
PFK1↓,
PDK1↓,
chemoP↓, The positive effects of combining propolis with chemotherapeutics include reduced cytotoxicity to peripheral blood leukocytes, liver, and kidney cells.
radioP↑, Their selective nature makes them suitable for protecting normal cells while inducing cell death in cancer cells during chemotherapy or radiotherapy.

2332- RES,    Resveratrol’s Anti-Cancer Effects through the Modulation of Tumor Glucose Metabolism
- Review, Var, NA
Glycolysis↓, Resveratrol reduces glucose uptake and glycolysis by affecting Glut1, PFK1, HIF-1α, ROS, PDH, and the CamKKB/AMPK pathway.
GLUT1↓, resveratrol reduces glycolytic flux and Glut1 expression by targeting ROS-mediated HIF-1α activation in Lewis lung carcinoma tumor-bearing mice
PFK1↓,
Hif1a↓, Resveratrol specifically suppresses the nuclear β-catenin protein by inhibiting HIF-1α
ROS↑, Resveratrol increases ROS production
PDH↑, leading to increased PDH activity, inhibiting HK and PFK, and downregulating PKM2 activity
AMPK↑, esveratrol elevated NAD+/NADH, subsequently activated Sirt1, and in turn activated the AMP-activated kinase (AMPK),
TumCG↓, inhibits cell growth, invasion, and proliferation by targeting NF-kB, Sirt1, Sirt3, LDH, PI-3K, mTOR, PKM2, R5P, G6PD, TKT, talin, and PGAM.
TumCI↓,
TumCP↓,
p‑NF-kB↓, suppressing NF-κB phosphorylation
SIRT1↑, Resveratrol activates the target subcellular histone deacetylase Sirt1 in various human tissues, including tumors
SIRT3↑,
LDH↓, decreases glycolytic enzymes (pyruvate kinase and LDH) in Caco2 and HCT-116 cells
PI3K↓, Resveratrol also targets “classical” tumor-promoting pathways, such as PI3K/Akt, STAT3/5, and MAPK, which support glycolysis
mTOR↓, AMPK activation further inhibits the mTOR pathway
PKM2↓, inhibiting HK and PFK, and downregulating PKM2 activity
R5P↝,
G6PD↓, G6PDH knockdown significantly reduced cell proliferation
TKT↝,
talin↓, induces apoptosis by targeting the pentose phosphate and talin-FAK signaling pathways
HK2↓, Resveratrol downregulates glucose metabolism, mainly by inhibiting HK2;
GRP78/BiP↑, resveratrol stimulates GRP-78, and decreases glucose uptake,
GlucoseCon↓,
ER Stress↑, resveratrol-induced ER-stress leads to apoptosis of CRC cells
Warburg↓, Resveratrol reverses the Warburg effect
PFK↓, leading to increased PDH activity, inhibiting HK and PFK, and downregulating PKM2 activity

2334- RES,    Glut 1 in Cancer Cells and the Inhibitory Action of Resveratrol as A Potential Therapeutic Strategy
- Review, Var, NA
GLUT1↓, resveratrol and other natural products as GLUT1 inhibitors
GlucoseCon↓, Inhibition of Glucose Uptake by Resveratrol
lactateProd↓, RSV were able to inhibit glucose uptake, lactate production, Akt, and mTOR signaling
Akt↓,
mTOR↓,
Dose↝, results suggest that RSV can behave differently according to the dose used and the cell type and the metabolic state
SIRT6↑, RSV induces the expression of silent information regulator-6 (SIRT6) in hypopharyngeal carcinoma FaDu cell line
PKM2↓, observed that RSV down-regulate pyruvate kinase 2 (PKM2) expression by inhibiting mTOR signaling and suppressed cancer metabolism
HK2↓, RSV showed a decrease in mRNA and protein levels of GLUT1, HK2, PFK1, and PKM2 which finally caused inhibition of aerobic glycolysis in a study of VEGF-angiogenesis in human umbilical vein endothelial cells
PFK1↓,
ChemoSen↑, combinatorial strategies that could use GLUT1 inhibitors such as RSV with anticancer conventional drugs for therapy are promising

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

3144- VitC,    Some characteristics of Rabbit muscle phosphofructokinase-1 inhibition by ascorbate
- in-vitro, Nor, NA
PFK1↓, We found that inhibition by ascorbate was PFK-1 concentration dependent
LDH↓, vitamin C specifically inhibits muscle isozymes of AK (adenylate kinase), LDH, and PFK-1


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 15

Results for Effect on Cancer/Diseased Cells:
ACLY↓,2,   ACSL1↓,1,   Akt↓,3,   p‑Akt↓,1,   AminoA↓,1,   AMPK↑,1,   Apoptosis↑,3,   ATP↓,4,   ATP:AMP↓,1,   Bcl-xL↓,1,   BG↓,1,   BioAv↑,1,   Casp2↑,2,   Casp3↑,2,   Casp8↑,1,   Casp9↑,2,   chemoP↓,1,   ChemoSen↑,7,   cMyc↓,2,   CPT1A↓,1,   Dose?,1,   Dose↑,1,   Dose↝,1,   Dose∅,1,   E-cadherin↑,1,   ECAR↓,1,   eff↑,2,   ENO1↓,1,   ER Stress↑,1,   p‑ERK↓,1,   FAO↓,1,   FASN↓,2,   FASN↑,1,   FBPase↑,1,   G6PD↓,1,   GAPDH↓,1,   glucoNG↑,1,   GlucoseCon↓,8,   GlucoseCon↑,1,   GLUT1↓,6,   GLUT2↓,2,   GLUT3↓,2,   GLUT4↓,1,   Glycolysis↓,8,   GPI↓,1,   GRP78/BiP↑,1,   HCAR1↓,1,   Hif1a↓,3,   HK1↓,1,   HK2↓,10,   IGF-1R↓,2,   JAK2↓,1,   Ki-67↓,1,   lactateProd↓,6,   LC3II↑,1,   LDH↓,2,   LDHA↓,4,   Mcl-1↓,2,   MCT1↓,1,   MCT4↓,1,   mTOR↓,3,   mTORC1↓,1,   NA↓,1,   NF-kB↓,1,   p‑NF-kB↓,1,   NO↓,1,   OCR↑,1,   other↓,1,   OXPHOS↓,1,   P53↑,1,   p62↓,1,   PDH↑,1,   PDK1↓,1,   PFK↓,1,   PFK1↓,14,   PFK2↓,3,   pH↑,1,   PI3K↓,4,   PKA↓,1,   PKM2↓,7,   PTEN↑,3,   Pyruv↓,1,   R5P↝,1,   radioP↑,1,   ROS↑,4,   SDH↑,1,   selectivity↑,1,   SIRT1↑,1,   SIRT3↑,1,   SIRT6↑,1,   Snail↓,1,   p‑STAT3↓,1,   p‑STAT5↓,1,   talin↓,1,   TCA↑,1,   TKT↝,1,   TPI↓,1,   TumCG↓,4,   TumCI↓,1,   TumCP↓,6,   Warburg↓,3,  
Total Targets: 101

Results for Effect on Normal Cells:
Glycolysis↓,1,   Hif1a↓,1,   HK2↓,1,   Inflam↓,1,   PFK1↓,1,   PKM2↓,1,   toxicity↓,1,  
Total Targets: 7

Scientific Paper Hit Count for: PFK1, Phosphofructokinase-1
3 Citric Acid
2 Baicalein
2 Resveratrol
1 Baicalin
1 Betulinic acid
1 Curcumin
1 diet FMD Fasting Mimicking Diet
1 Chemotherapy
1 Ivermectin
1 Phenylbutyrate
1 Propolis -bee glue
1 Shikonin
1 Vitamin C (Ascorbic Acid)
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:%  Target#:988  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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