PFK Cancer Research Results

PFK, Phosphofructokinase: Click to Expand ⟱

Source:

Type:

PFK (Phosphofructokinase) is a key enzyme in glycolysis, the process by which cells convert glucose into energy. PFK is overexpressed in many types of cancer, and its expression is often associated with poor prognosis.
Mechanisms:
• PFK promotes glycolysis, which is a key metabolic pathway in cancer cells.
• PFK helps to produce energy for cancer cells.
• PFK promotes cell proliferation.

Therapeutic Targeting:
• PFK inhibitors are being developed as a potential therapeutic strategy for cancer treatment.
• Inhibitors of glycolysis, such as 2-deoxyglucose, are being explored as a potential therapeutic strategy for cancer treatment.

Scientific Papers found: Click to Expand⟱

3454-

ALA,

Lipoic acid blocks autophagic flux and impairs cellular bioenergetics in breast cancer and reduces stemness

in-vitro,

BC,

MCF-7

(0.5 mM, 1 mM, 2.5 mM, and 5 mM)

in-vitro,

BC,

MDA-MB-231

TumCG↑, Lipoic acid inhibits breast cancer cell growth via accumulation of autophagosomes.
Glycolysis↓, Lipoic acid inhibits glycolysis in breast cancer cells.
ROS↑, Lipoic acid induces ROS production in breast cancer cells/BCSC.
CSCs↓, Here, we demonstrate that LA inhibits mammosphere formation and subpopulation of BCSCs
selectivity↑, In contrast, LA at similar doses. had no significant effect on the cell viability of the human embryonic kidney cell line (HEK-293)
LC3B-II↑, LA treatment (0.5 mM and 1.0 mM) increased the expression level of LC3B-I to LC3B-II in both MCF-7 and MDA-MB231cells at 48 h
MMP↓, LA induced mitochondrial ROS levels, decreased mitochondria complex I activity, and MMP in both MCF-7 and MDA-MB231 cells
mitResp↓, In MCF-7 cells, we found a substantial reduction in maximal respiration and ATP production at 0.5 mM and 1 mM of LA treatment after 48 h
ATP↓,
OCR↓, LA at 2.5 mM decreased OCR
NAD↓, we found that LA (0.5 mM and 1 mM) significantly reduced ATP production and NAD levels in MCF-7 and MDA-MB231 cells
p‑AMPK↑, LA treatment (0.5 mM and 1.0 mM) increased p-AMPK levels;
GlucoseCon↓, LA (0.5 mM and 1 mM) significantly decreased glucose uptake and lactate production in MCF-7, whereas LA at 1 mM significantly reduced glucose uptake and lactate production in MDA-MB231 cells but it had no effect at 0.5 mM
lactateProd↓,
HK2↓, LA reduced hexokinase 2 (HK2), phosphofructokinase (PFK), pyruvate kinase M2 (PKM2), and lactate dehydrogenase A (LDHA) expression in MCF-7 and MDA-MB231 cells
PFK↓,
LDHA↓,
eff↓, Moreover, we found that LA-mediated inhibition of cellular bioenergetics including OCR (maximal respiration and ATP production) and glycolysis were restored by NAC treatment (Fig. 6E and F) which indicates that LA-induced ROS production is responsibl
mTOR↓, LA inhibits mTOR signaling and thereby decreased the p-TFEB levels in breast cancer cells
ECAR↓, LA also inhibits glycolysis as evidenced by decreased glucose uptake, lactate production, and ECAR.
ALDH↓, LA decreased ALDH1 activity, CD44+/CD24-subpopulation, and increased accumulation of autophagosomes possibly due to inhibition of autophagic flux of breast cancer.
CD44↓,
CD24↓,

1640-

CA,

MET,

Caffeic Acid Targets AMPK Signaling and Regulates Tricarboxylic Acid Cycle Anaplerosis while Metformin Downregulates HIF-1α-Induced Glycolytic Enzymes in Human Cervical Squamous Cell Carcinoma Lines

in-vitro,

Cerv,

SiHa

GLS↓, downregulation of Glutaminase (GLS) and Malic Enzyme 1 (ME1)
NADPH↓, CA alone and co-treated with Met caused significant reduction of NADPH
ROS↑, increased ROS formation and enhanced cell death
TumCD↑,
AMPK↑, activation of AMPK
Hif1a↓, Met inhibited Hypoxia-inducible Factor 1 (HIF-1α). CA treatment at 100 μM for 24 h also inhibited HIF-1α
GLUT1↓,
GLUT3↓,
HK2↓,
PFK↓, PFKFB4
PKM2↓,
LDH↓,
cMyc↓, Met suppressed the expression of c-Myc, BAX and cyclin-D1 (CCND1) a
BAX↓,
cycD1/CCND1↓,
PDH↓, CA at a concentration of 100 µM caused inhibition of PDK activity
ROS↑, CA Regulates TCA Cycle Supply via Pyruvate Dehydrogenase Complex (PDH), Induces Mitochondrial ROS Generation and Evokes Apoptosis
Apoptosis↑,
eff↑, both drugs inhibited the expression of ACLY and FAS, but the greatest effect was detected after co-treatment
ACLY↓,
FASN↓,
Bcl-2↓,
Glycolysis↓, Met acts as a glycolytic inhibitor under normoxic and hypoxic conditions

1593-

Citrate,

Citrate Induces Apoptotic Cell Death: A Promising Way to Treat Gastric Carcinoma?

in-vitro,

GC,

BGC-823

10mM

in-vitro,

GC,

SGC-7901

PFK↓, citrate, a strong physiological inhibitor of phosphofructokinase (PFK)
Glycolysis↓, citrate is a strong inhibitor of glycolysis
tumCV↓, 10 mM citrate led to a nearly complete disappearance of cancer cells, and after 72 h, no cells remained viable whatever the concentration used
cl‑Casp3↑,
cl‑PARP↑,
Apoptosis↑,
ATP↓, depletion of ATP generated by citrate
ChemoSen↑, In the previous study, citrate sensitized the cells to cisplatin, a drug which was poorly efficient by itself on such cells
Mcl-1↓, In the current study, citrate reduced MCL-1 expression in both the gastric cancer lines in a dose-dependent manner, in agreement with previous observations in mesothelioma cells
glucoNG↑, citrate activates neoglucogenesis by enhancing fructose 1,6-bisphosphatase activity
FBPase↑,
OXPHOS↓, When citrate is abundant in cells, this usually means that energy production (ATP) is sufficient, so oxidative phosphorylation (OXPHOS) and the Krebs cycle are slowed down or stopped.
TCA↓, Krebs cycle are slowed down or stopped.
β-oxidation↓, concomitantly inhibits β-oxidation
HK2↓, It may inhibit HK, at least indirectly, by the physiological retroaction of glucose-6-phosphate (G6P) on HK
PDH↓, citrate may inhibit pyruvate dehydrogenase (PDH) (39), the enzyme of the Krebs cycle which links glycolysis and the tricarboxylic cycle
ROS↑, citrate could also promote the formation of reactive oxygen species (ROS) since a sudden elevation of citrate concentration inside the cell might immediately stimulate the Krebs cycle.

1579-

Citrate,

Effect of Food Additive Citric Acid on The Growth of Human Esophageal Carcinoma Cell Line EC109

in-vitro,

ESCC,

Eca109

TumCP↓, higher citric acid concentrations (800, 1600 μg/ml)
e-LDH↑, incubation with either 400, 800 or 1600 µg/ml CA for 48 hours caused a significant increase (P<0.01) in LDH release by 1.67-fold, 2.79fold and 3.16-fold, respectively
MMP↓,
Ca+2?, CA level can directly regulate several metabolic pathways and increase calcium uptake from foods
PFK↓, potential inhibitor of PFK
Glycolysis↓, increasingly evidences have indicated that a high level of citrate could inhibit the glycolytic pathway

989-

EGCG,

Citrate,

In vitro and in vivo study of epigallocatechin-3-gallate-induced apoptosis in aerobic glycolytic hepatocellular carcinoma cells involving inhibition of phosphofructokinase activity

in-vitro,

HCC,

EGCG (50 μM), citrate (5 mM)

in-vivo,

NA,

10 mg/kg/ BW/day

mice

PFK↓,
Glycolysis↓, only inhibited glycolysis in cancer cells with a high rate of aerobic glycolysis (HCC-LM3 and HepG2 cells) but not in low-glycolytic cells (Huh-7 and LO2 cells).
lactateProd↓,
GlucoseCon↓,
TumCP↓,
TumCCA↑, arrests cells in S Phage
Casp3↑, citrate enhanced the EGCG upregulation of active caspase-3 and cleaved-PARP in both HCC-LM3 and HepG2 cells
cl‑PARP↑,
Apoptosis↑,
Casp8↑,
Casp9↑,
Cyt‑c↝, translocation of cytochrome c from the mitochondria into the cytosol
MMP↓,
BAD↑,
GLUT2↓, figure2 c,d
PKM2∅, figure2 c,d

2302-

EGCG,

Flavonoids Targeting HIF-1: Implications on Cancer Metabolism

Review,

Var,

TumCP↓, EGCG suppressed proliferation and dose-dependently inhibited the expression of HIF-1α
Hif1a↓, EGCG significantly suppressed HIF-1α protein accumulation in these cells but did not affect HIF-1α mRNA expression.
LDHA↓, Moreover, EGCG attenuated LDHA release in Sarcoma 180 tumor-bearing mice
PFK↓, Moreover, EGCG inhibited the expression and activity of PFK in hepatocellular carcinoma (HCC-LM3 and HepG2) cells
cardioP↑, EGCG-exerted heart benefits related to reduced LDH release
Glycolysis↓, EGCG inhibits glycolysis (especially PFK activity) in aerobic glycolytic HCC cell lines
PKM2↓, EGCG inhibits glycolysis through repressing rate-limiting enzymes (PFK and PKM2)

2309-

EGCG,

Chemo,

Targeting Glycolysis with Epigallocatechin-3-Gallate Enhances the Efficacy of Chemotherapeutics in Pancreatic Cancer Cells and Xenografts

in-vitro,

PC,

MIA PaCa-2

(20–100 μM) for 72 h

in-vitro,

Nor,

HPNE

in-vitro,

PC,

PANC1

in-vivo,

NA,

mice

TumCG↓, EGCG reduced pancreatic cancer cell growth in a concentration-dependent manner
eff↑, and the growth inhibition effect was further enhanced under glucose deprivation conditions.
ROS↑, EGCG at 40 µM increased ROS levels by 1.4- and 1.6-fold in Panc-1 and MIA PaCa-2 cells, respectively
ECAR↓, EGCG affected glycolysis by suppressing the extracellular acidification rate through the reduction of the activity and levels of the glycolytic enzymes phosphofructokinase and pyruvate kinase.
ChemoSen↑, EGCG sensitized gemcitabine to inhibit pancreatic cancer cell growth in vitro and in vivo.
selectivity↑, EGCG at 80 µM for 72 h had significantly less effect on the HPNE cells, reducing cell growth by only 24%
Glycolysis↓, EGCG Inhibits Glycolysis through Suppressing Rate-Limiting Enzymes. EGCG Plus Gemcitabine Further Inhibits Glycolysis
PFK↓, EGCG treatment reduced both the activity and expression levels of phosphofructokinase (PFK) and pyruvate kinase (PK) in Panc-1 and MIA PaCa-2 cells
PKA↓,
HK2∅, EGCG failed to reduce hexokinases II (HK2) and lactate dehydrogenase A (LDHA) protein expression levels
LDHA∅,
PFKP↓, EGCG reduced the levels of PFKP and PKM2 (p < 0.01 for both) in pancreatic tumor xenograft homogenates, obtained from mice treated with EGCG
PKM2↓,
H2O2↑, EGCG at 40 µM increased H2O2 levels by 1.5- and 1.9-fold in Panc-1 and MIA PaCa-2 cells
TumW↓, EGCG and gemcitabine, given as single agents, reduced tumor weight by 40% and 52%, respectively, compared to vehicle-treated controls (p < 0.05 and p < 0.01). In combination, EGCG plus gemcitabine reduced tumor weight by 67%,

2512-

H2,

Hydrogen Attenuates Allergic Inflammation by Reversing Energy Metabolic Pathway Switch

in-vivo,

asthmatic,

selectivity↑, we treated mice with HRS for 7 days. HRS had no effects on OXPHOS and glycolytic activities in control mice
lactateProd↓, but prevented the elevation in lactate and reduction in ATP production in lungs of OVA-sensitized and challenged mice
ATP↑,
HK2↓, Consistently, HRS attenuated the increase in HK and PFK activities
PFK↓,
Hif1a↓, OVA sensitization and challenge increased HIF-1α nuclear translocation (stimulated HIF-1α activity), which was inhibited by HRS treatment
PGC-1α↑, By contrast, OVA sensitization and challenge downregulated PGC-1α protein expression, and HRS treatment reversed this downregulation
Glycolysis↓, H2 reverses energy metabolic switch by inhibiting glycolytic enzyme activities and by stimulating mitochondrial OXPHOS enzyme activities
OXPHOS↑,
Dose↝, HRS was prepared by dipping a plastic-shelled stick consisting of metallic magnesium (99.9% pure) and natural stones (Doctor SUISOSUI, Friendear Inc., Tokyo, Japan) into sterilized saline.

991-

OA,

Blockade of glycolysis-dependent contraction by oroxylin a via inhibition of lactate dehydrogenase-a in hepatic stellate cells

in-vivo,

NA,

40 mg/kg

fibrotic mice

in-vivo,

Nor,

cultured human HSCs

*Glycolysis↓, Oroxylin A blocked aerobic glycolysis in HSCs evidenced by reduction in glucose uptake and consumption and lactate production
*GlucoseCon↓,
*lactateProd↓,
*ECAR↓,
*HK2↓,
*PFK↓, phosphofructokinase 1
*PKM2↓,
*LDHA↓, inhibited the expression and activity of lactate dehydrogenase-A (LDH-A)

2396-

PACs,

PKM2 is the target of proanthocyanidin B2 during the inhibition of hepatocellular carcinoma

in-vitro,

HCC,

HCCLM3

80.59 μM

in-vitro,

HCC,

SMMC-7721 cell

76.32 μM

in-vitro,

HCC,

Bel-7402

in-vitro,

HCC,

HUH7

in-vitro,

HCC,

HepG2

in-vitro,

Nor,

L02

TumCP↓, PB2 inhibited the proliferation, induced cell cycle arrest, and triggered apoptosis of HCC cells in vivo and in vitro.
TumCCA↓,
Apoptosis↑,
GlucoseCon↓, PB2 also suppressed glucose uptake and lactate levels via the direct inhibition of the key glycolytic enzyme, PKM2.
lactateProd↓,
PKM2↓,
Glycolysis↓, to suppress aerobic glycolysis
HK2↓, PB2 suppressed the expression of HK2, PFKFB3, and PKM2, while enhancing the expression of OXPHOS in both HCC-LM3 and SMMC-7721 cells
PFK↓,
OXPHOS↑, PB2 inhibited aerobic glycolysis and improved OXPHOS in HCC cell lines
ChemoSen↑, PB2 enhanced the chemosensitivity of SORA on HCC, both in vivo and in vitro
HSP90↓, PB2 reduced the expressions of both HSP90 and HIF-1α in a dose-dependent manner in HCC cells
Hif1a↓,

1231-

PBG,

Caffeic acid phenethyl ester inhibits MDA-MB-231 cell proliferation in inflammatory microenvironment by suppressing glycolysis and lipid metabolism

in-vitro,

BC,

MDA-MB-231

TumCP↓,
TumCMig↓,
TumCI↓,
MMP↓,
TLR4↓,
TNF-α↓,
NF-kB↓,
IL1β↓,
IL6↓,
IRAK4↓,
GLUT1↓,
GLUT3↓,
HK2↓,
PFK↓,
PKM2↓,
LDHA↓,
ACC↓,
FASN↓,
eff↓, After adding the glycolysis inhibitor 2-deoxy-D-glucose (2-DG), the inhibitory effects of CAPE on cell viability and migration were not significant when compared with the LPS group.

1672-

PBG,

The Potential Use of Propolis as an Adjunctive Therapy in Breast Cancers

Review,

BC,

ChemoSen↓, 4 human clinical trials that demonstrated the successful use of propolis in alleviating side effects of chemotherapy and radiotherapy while increasing the quality of life of breast cancer patients, with minimal adverse effects.
RadioS↑,
Inflam↓, immunomodulatory, anti-inflammatory, and anti-cancer properties.
AntiCan↑,
Dose∅, Indonesia: IC50 = 4.57 μg/mL and 10.23 μg/mL
mtDam↑, Poland: propolis induced mitochondrial damage and subsequent apoptosis in breast cancer cells.
Apoptosis?,
OCR↓, China: CAPE inhibited mitochondrial oxygen consumption rate (OCR) by reducing basal, maximal, and spare respiration rate and consequently inhibiting ATP production
ATP↓,
ROS↑, Iran: inducing intracellular ROS production, IC50 = 65-96 μg/mL
ROS↑, Propolis induced mitochondrial dysfunction and lactate dehydrogenase release indicating the occurrence of ROS-associated necrosis.
LDH↓,
TP53↓, Interestingly, a reduced expression of apoptosis-related genes such as TP53, CASP3, BAX, and P21)
Casp3↓,
BAX↓,
P21↓,
ROS↑, CAPE: inducing oxidative stress through upregulation of e-NOS and i-NOS levels
eNOS↑,
iNOS↑,
eff↑, The combination of propolis and mangostin significantly reduced the expression of Wnt2, FAK, and HIF-1α, when compared to propolis or mangostin alone
hTERT/TERT↓, downregulation of the mRNA levels of hTERT and cyclin D1
cycD1/CCND1↓,
eff↑, Synergism with bee venom was observed
eff↑, Statistically significant decrease was found in the MCF-7 cell viability 48 h after applying different combinations of cisplatin (3.12 μg/mL) and curcumin (0.31 μg/mL) and propolis (160 μg/mL)
eff↑, Nanoparticles of chrysin had significantly higher cytotoxicity against MCF-7 cells, compared to chrysin
eff↑, Propolis nanoparticles appeared to increase cytotoxicity of propolis against MCF-7 cells
STAT3↓, Chrysin also inhibited the hypoxia-induced STAT3 tyrosine phosphorylation suggesting the mechanism of action was through STAT3 inhibition.
TIMP1↓, Propolis reduced the expression of TIMP-1, IL-4, and IL-10.
IL4↓,
IL10↓,
OS↑, patients supplemented with propolis had significantly longer median disease free survival time (400 mg, 3 times daily for 10 d pre-, during, and post)
Dose∅, 400 mg, 3 times daily for 10 d pre-, during, and post
ER Stress↑, endoplasmic reticulum stress
ROS↑, upregulating the expression of Annexin A7 (ANXA7), reactive oxygen species (ROS) level, and NF-κB p65 level, while simultaneously reducing the mitochondrial membrane potential.
NF-kB↓,
p65↓,
MMP↓,
TumAuto↑, propolis induced autophagy by increasing the expression of LC3-II and reducing the expression of p62 level
LC3II↑,
p62↓,
TLR4↓, propolis downregulates the inflammatory TLR4
mtDam↑, propolis induced mitochondrial dysfunction and lactate dehydrogenase release indicating ROS-associated necrosis in MDA MB-231cancer cells
LDH↓,
ROS↑,
Glycolysis↓, inhibit the proliferation of MDA-MB-231 cells by targeting key enzymes of glycolysis, namely glycolysis-hexokinase 2 (HK2), phosphofructokinase (PFK), pyruvate kinase muscle isozyme M2 (PKM2), and lactate dehydrogenase A (LDHA),
HK2↓,
PFK↓,
PKM2↓,
LDH↓,
IL10↓, propolis significantly reduced the relative number of CD4+, CD25+, FoxP3+ regulatory T cells expressing IL-10
HDAC8↓, Chrysin, a propolis bioactive compound, inhibits HDAC8
eff↑, combination of propolis and mangostin significantly reduced the expression of Wnt2, FAK, and HIF-1α, when compared to propolis or mangostin alone.
eff↑, Propolis also upregulated the expression of catalase, HTRA2/Omi, FADD, and TRAIL-associated DR5 and DR4 which significantly enhanced the cytotoxicity of doxorubicin in MCF-7 cells
P21↑, Chrysin, a propolis bioactive compound, inhibits HDAC8 and significantly increases the expression of p21 (waf1/cip1) in breast cancer cells, leading to apoptosis.

1661-

PBG,

Propolis: a natural compound with potential as an adjuvant in cancer therapy - a review of signaling pathways

Review,

Var,

JNK↓, downregulating pathways involving Jun-N terminal kinase, ERK1/2, Akt and NF-ƘB
ERK↓,
Akt↓,
NF-kB↓,
FAK↓, inhibiting Wtn2 and FAK, and MAPK and PI3K/AKT signaling pathways
MAPK↓,
PI3K↓,
Akt↓,
P21↑, propolis-induced up-regulation of p21 and p27
p27↑,
TRAIL↑, effects of propolis are mediated through upregulation of TRAIL, Bax, p53, and downregulation of the ERK1/2 signaling
BAX↑,
P53↑,
ERK↓,
ChemoSen↑, effective adjuvant therapy aimed at reducing related side effects associated with chemotherapy and radiotherapy
RadioS↑,
Glycolysis↓, Chinese poplar propolis decreased aerobic glycolysis by reducing the levels of crucial enzymes such as phosphofructokinase (PFK), hexokinase 2 (HK2), pyruvate kinase M2 (PKM2), and lactate dehydrogenase A (LDHA)
HK2↓,
PKM2↓,
LDHA↓,
PFK↓,

1664-

PBG,

Anticancer Activity of Propolis and Its Compounds

Review,

Var,

Apoptosis↑,
TumCMig↓,
TumCCA↑,
TumCP↓,
angioG↓,
P21↑, upregulating p21 and p27 expression
p27↑,
CDK1↓, thanol-extracted Cameroonian propolis increased the amount of DU145 and PC3 cells in G0/G1 phase, down-regulated cell cycle proteins (CDK1, pCDK1, and their related cyclins A and B)
p‑CDK1↓,
cycA1/CCNA1↓,
CycB/CCNB1↓,
P70S6K↓, Caffeic acid phenylethyl ester has been shown to inhibit the S6 beta-1 ribosomal protein kinase (p70S6K),
CLDN2↓, inhibition of NF-κB may be involved in the decrease of claudin-2 mRNA level
HK2↓, Chinese poplar propolis has been shown to significantly reduce the level of glycolysis at the stage of action of hexokinase 2 (HK2), phosphofructokinase (PFK), muscle isozyme pyruvate kinase M2 (PKM2), and lactate dehydrogenase A (LDHA)
PFK↓,
PKM2↓,
LDHA↓,
TLR4↓, hinese propolis, as well as CAPE, inhibits breast cancer cell proliferation in the inflammatory microenvironment by inhibiting the Toll-like receptor 4 (TLR4) signal pathway
H3↓, Brazilian red propolis bioactive isoflavonoid, down-regulates the alpha-tubulin, tubulin in microtubules, and histone H3 genes
α-tubulin↓,
ROS↑, CAPE also affects the apoptotic intrinsic pathway by increasing ROS production
Akt↓, CAPE induces apoptosis by decreasing the levels of proteins related to carcinogenesis, including Akt, GSK3b, FOXO1, FOXO3a, NF-kB, Skp2 and cyclin D1
GSK‐3β↓,
FOXO3↓,
NF-kB↓,
cycD1/CCND1↓,
MMP↓, It was found that chrysin caused a loss of mitochondria membrane potential (MMP) while increasing the production of reactive oxygen species (ROS), cytoplasmic Ca2+ levels, and lipid peroxidation
ROS↑,
i-Ca+2↑,
lipid-P↑,
ER Stress↑, Chrysin also induced endoplasmic reticulum (ER) stress by activating unfolded protein response proteins (UPR) such as PRKR-like ER kinase (PERK), eukaryotic translation initiation factor 2α (eIF2α), and 78 kDa glucose-regulated protein (GRP78)
UPR↑,
PERK↑,
eIF2α↑,
GRP78/BiP↑,
BAX↑, CAPE activated Bax protein
PUMA↑, CAPE also significantly increased PUMA expression
ROS↑, Northeast China causes cell apoptosis in human gastric cancer cells with increased production of reactive oxygen species (ROS) and reduced mitochondrial membrane potential.
MMP↓,
Cyt‑c↑, release of cytochrome C from mitochondria to the cytoplasm is observed, as well as the activation of cleaved caspases (8, 9, and 3) and PARP
cl‑Casp8↑,
cl‑Casp8↑,
cl‑Casp3↑,
cl‑PARP↑,
eff↑, administration of Iranian propolis extract in combination with 5-fluorouracil (5-FU) significantly reduced the number of azaxymethane-induced aberrant crypt foci compared to 5-FU or propolis alone.
eff↑, Propolis may also have a positive effect on the efficacy of photodynamic therapy (PDT). enhances the intracellular accumulation of protoporphyrin IX (PpIX) in human epidermoid carcinoma cells
RadioS↑, breast cancer patients undergoing radiotherapy and supplemented with propolis had a statistically significant longer median disease-free survival time than the control group
ChemoSen↑, confirmed that propolis mouthwash is effective and safe in the treatment of chemo- or radiotherapy-induced oral mucositis in cancer patients.
eff↑, Quercetin, ferulic acid, and CAPE may also influence the MDR of cancer cells by inhibiting P-gp expression

2382-

PBG,

Integration with Transcriptomic and Metabolomic Analyses Reveals the In Vitro Cytotoxic Mechanisms of Chinese Poplar Propolis by Triggering the Glucose Metabolism in Human Hepatocellular Carcinoma Cells

in-vitro,

HCC,

HepG2

TumCP↓, Our evidence suggested that CP possesses a great potential to inhibit the proliferation of HepG2 cells by targeting the glucose metabolism.
Glycolysis↓,
GlucoseCon↓, CP effectively restrained glucose consumption and lactic acid production.
lactateProd↓,
GLUT1↓, CP treatment led to a substantial decrease in the mRNA expression levels of key glucose transporters (GLUT1 and GLUT3) and glycolytic enzymes (LDHA, HK2, PKM2, and PFK).
GLUT2↓,
LDHA↓,
HK2↓,
PKM2↓,
PFK↓,
Dose↝, key compounds in CP were screened, and apigenin, pinobanksin, pinocembrin, and galangin were identified as potential active agents against glycolysis.

2381-

PBG,

Chinese Poplar Propolis Inhibits MDA-MB-231 Cell Proliferation in an Inflammatory Microenvironment by Targeting Enzymes of the Glycolytic Pathway

in-vitro,

BC,

MDA-MB-231

0-100ug/mL

TumCP↓, Propolis treatment obviously inhibited MDA-MB-231 cell proliferation, migration and invasion, clone forming, and angiogenesis.
TumCMig↓,
TumCI↓,
angioG↓,
TNF-α↓, (TNF-α), interleukin (IL)-1β, and IL-6, as well as NLRP3 inflammasomes, were decreased following propolis treatment when compared with the LPS group.
IL1β↓,
IL6↓,
NLRP3↓,
Glycolysis↓, Moreover, propolis treatment significantly downregulated the levels of key enzymes of glycolysis–hexokinase 2 (HK2), phosphofructokinase (PFK), pyruvate kinase muscle isozyme M2 (PKM2), and lactate dehydrogenase A (LDHA) in MDA-MB-231 cells
HK2↓,
PFK↓,
PKM2↓,
LDHA↓,
ROS↑, propolis increased reactive oxygen species (ROS) levels and decreased mitochondrial membrane potential.
MMP↓,

2332-

RES,

Resveratrol’s Anti-Cancer Effects through the Modulation of Tumor Glucose Metabolism

Review,

Var,

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

3092-

RES,

Resveratrol in breast cancer treatment: from cellular effects to molecular mechanisms of action

Review,

BC,

MDA-MB-231

Review,

BC,

MCF-7

TumCP↓, The anticancer mechanisms of RES in regard to breast cancer include the inhibition of cell proliferation, and reduction of cell viability, invasion, and metastasis.
tumCV↓,
TumCI↓,
TumMeta↓,
*antiOx↑, antioxidative, cardioprotective, estrogenic, antiestrogenic, anti-inflammatory, and antitumor properties it has been used against several diseases, including diabetes, neurodegenerative diseases, coronary diseases, pulmonary diseases, arthritis, and
*cardioP↑,
*Inflam↓,
*neuroP↑,
*Keap1↓, RES administration resulted in a downregulation of Keap1 expression, therefore, inducing Nrf2 signaling, and leading to a decrease in oxidative damage
*NRF2↑,
*ROS↓,
p62↓, decrease the severity of rheumatoid arthritis by inducing autophagy via p62 downregulation, decreasing the levels of interleukin-1β (IL-1β) and C-reactive protein as well as mitigating angiopoietin-1 and vascular endothelial growth factor (VEGF) path
IL1β↓,
CRP↓,
VEGF↓,
Bcl-2↓, RES downregulates the levels of Bcl-2, MMP-2, and MMP-9, and induces the phosphorylation of extracellular-signal-regulated kinase (ERK)/p-38 and FOXO4
MMP2↓,
MMP9↓,
FOXO4↓,
POLD1↓, The in vivo experiment involving a xenograft model confirmed the ability of RES to reduce tumor growth via POLD1 downregulation
CK2↓, RES reduces the expression of casein kinase 2 (CK2) and diminishes the viability of MCF-7 cells.
MMP↓, Furthermore, RES impairs mitochondrial membrane potential, enhances ROS generation, and induces apoptosis, impairing BC progression
ROS↑,
Apoptosis↑,
TumCCA↑, RES has the capability of triggering cell cycle arrest at S phase and reducing the number of 4T1 BC cells in G0/G1 phase
Beclin-1↓, RES administration promotes cytotoxicity of DOX against BC cells by downregulating Beclin-1 and subsequently inhibiting autophagy
Ki-67↓, Reducing the Ki-67
ATP↓, RES’s administration is responsible for decreasing ATP production and glucose metabolism in MCF-7 cells.
GlutMet↓,
PFK↓, RES decreased PFK activity, preventing glycolysis and glucose metabolism in BC cells and decreasing cellular growth rate
TGF-β↓, RES (12.5–100 µM) inhibited TGF-β signaling and reduced the expression levels of its downstream targets that include Smad2 and Smad3 and as a result impaired the progression of BC cells.
SMAD2↓,
SMAD3↓,
Vim?, a significant decrease in the levels of vimentin, Snail1 and Slug occurred, while E-cadherin levels increased to suppress EMT and metastasis of BC cells.
Snail↓,
Slug↓,
E-cadherin↑,
EMT↓,
Zeb1↓, a significant decrease in the levels of vimentin, Snail1 and Slug occurred, while E-cadherin levels increased to suppress EMT and metastasis of BC cells.
Fibronectin↓,
IGF-1↓, RES administration (10 and 20 µM) impaired the migration and invasion of BC cells via inhibiting PI3K/Akt and therefore decreasing IGF-1 expression and preventing the upregulation of MMP-2
PI3K↓,
Akt↓,
HO-1↑, The activation of heme oxygenase-1 (HO-1) signaling by RES reduced MMP-9 expression and prevented metastasis of BC cells
eff↑, RES-loaded gold nanoparticles were found to enhance RES’s ability to reduce MMP-9 expression as compared to RES alone
PD-1↓, RES inhibited PD-1 expression to promote CD8+ T cell activity and enhance Th1 immune responses.
CD8+↑,
Th1 response↑,
CSCs↓, RES has the ability to target CSCs in various tumors
RadioS↑, RES in reversing drug resistance and radio resistance.
SIRT1↑, RES administration (12.5–200 µmol/L) promotes sensitivity of BC cells to DOX by increasing Sirtuin 1 (SIRT1) expression
Hif1a↓, downregulating HIF-1α expression, an important factor in enhancing radiosensitivity
mTOR↓, mTOR suppression

1913-

Xyl,

Partial Substitution of Glucose with Xylitol Prolongs Survival and Suppresses Cell Proliferation and Glycolysis of Mice Bearing Orthotopic Xenograft of Oral Cancer

in-vivo,

Oral,

mice

TumVol↓, partial substitution of glucose with xylitol (glucose 0.35 g plus xylitol 2.06 g/kg body weight) non-significantly reduced tumor volume,
OS↑, and significantly prolonged the median survival time from 19 days in the control to 30.5 days
PFK↓, showed a non-significant inhibition of PFK activity
toxicity↓, No Significant Differences in Body Weights and No Adverse Effects in Weight Loss of Xylitol-Treated Mice, Compared to the Control Group
Dose∅, Such dose is equivalent to 0.1–0.2 g/kg body weight or 10 g/day in humans
Ki-67↓, proliferation marker Ki-67 tended to reduce in xylitol-treated groups

2425-

γ-Toc,

Anticancer Effects of γ-Tocotrienol Are Associated with a Suppression in Aerobic Glycolysis

in-vitro,

NA,

MCF-7

 6–8 µM

in-vivo,

NA,

mouse

TumCG↓, Treatment with γ-tocotrienol resulted in a dose-responsive inhibition of both +SA and MCF-7 mammary tumor cell growth
GlucoseCon↓, induced a relatively large reduction in glucose utilization, intracellular ATP production and extracellular lactate excretion.
ATP↓,
lactateProd↓,
Glycolysis↓, These effects were also associated with a large decrease in enzyme expression levels involved in regulating aerobic glycolysis
HK2↓, including hexokinase-II, phosphofructokinase, pyruvate kinase M2, and lactate dehydrogenase A
PFK↓,
PKM2↓,
LDHA↓,
Akt↓, γ-Tocotrienol treatment was also associated with a corresponding reduction in the levels of phosphorylated (active) Akt, phosphorylated (active) mTOR, and c-Myc
p‑mTOR↓,
cMyc↓,

Showing Research Papers: 1 to 20 of 20

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 20

Pathway results for Effect on Cancer / Diseased Cells:

Infection & Microbiome ⓘ

CD8+↑, 1,
Total Targets: 187

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 1, Keap1↓, 1, NRF2↑, 1, ROS↓, 1,

Core Metabolism/Glycolysis ⓘ

ECAR↓, 1, GlucoseCon↓, 1, Glycolysis↓, 1, HK2↓, 1, lactateProd↓, 1, LDHA↓, 1, PFK↓, 1, PKM2↓, 1,

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,

Functional Outcomes ⓘ

cardioP↑, 1, neuroP↑, 1,
Total Targets: 15

Scientific Paper Hit Count for: PFK, Phosphofructokinase

6 Propolis -bee glue
3 Citric Acid
3 EGCG (Epigallocatechin Gallate)
2 Resveratrol
1 Alpha-Lipoic-Acid
1 Caffeic acid
1 Metformin
1 Chemotherapy
1 Hydrogen Gas
1 Oroxylin-A
1 Proanthocyanidins
1 Xylitol
1 γ-Tocotrienol

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

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:%  Target#:945  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

PFK Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Core Metabolism/Glycolysis ⓘ

Immune & Inflammatory Signaling ⓘ

Functional Outcomes ⓘ

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