HK2 Cancer Research Results

HK2, Hexokinase 2: Click to Expand ⟱

Source:

Type: enzyme

HK2 (Hexokinase 2) is an enzyme that plays a crucial role in glycolysis, the process by which cells convert glucose into energy. HK2 is a key regulatory enzyme in the glycolytic pathway, and it is primarily expressed in various tissues, including muscle, brain, and cancer cells.
HK2 has been shown to be overexpressed in many types of tumors, including breast, lung, and colon cancer. This overexpression may contribute to the development and progression of cancer by promoting glycolysis and energy production in cancer cells.
HK2 is a key regulatory enzyme in the glycolytic pathway.
HK2 plays a role in the regulation of glucose metabolism in diabetes.
HK2 is involved in the regulation of cell proliferation, apoptosis, and autophagy.

HK2 Inhibitors:
-2DG
-Curcumin
-Resveratrol
-EGCG
-Berberine
-Methyl Jasmonate (MJ)
-Honokiol

Scientific Papers found: Click to Expand⟱

2435-

2DG,

Targeting hexokinase 2 for oral cancer therapy: structure-based design and validation of lead compounds

in-vitro,

SCC,

CAL27

MMP↓, inhibition of HK2 led to the loss of mitochondrial membrane potential and increased mitophagy as a potential mechanism of anticancer action.
HK2↓, standard HK2 inhibitor 2-deoxyglucose (2-DG

2325-

2DG,

Research Progress of Warburg Effect in Hepatocellular Carcinoma

Review,

Var,

HK2↓, 2-Deoxyglucose (2-DG) is a widely studied HK2 inhibitor that has been reported to inhibit glycolysis by inhibiting hexokinase
Glycolysis↓,
PKM2↓, In rat HCC models, 2-DG was shown to reduce PKM2 and LDHA expression, leading to decreased aerobic glycolysis and tumor cell death
LDHA↓,
TumCD↑,
ChemoSen↑, Combining 2-DG with sorafenib demonstrated superior antitumor effects compared to sorafenib alone, suggesting its potential for synergistic action with other anticancer drugs
eff↑, Moreover, DHA combined with 2-DG can reportedly induce apoptosis in A549 and PC-9 cells

2327-

2DG,

2-Deoxy-d-Glucose and Its Analogs: From Diagnostic to Therapeutic Agents

Review,

Var,

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

2432-

2DG,

Inhibition of glycolytic enzyme hexokinase II (HK2) suppresses lung tumor growth

in-vitro,

Lung,

H23

in-vitro,

Lung,

KP2

in-vivo,

NA,

HK2↓, 2-DG, an inhibitor of HK2, inhibited human and mouse lung cancer cell growth through inducing cell apoptosis and autophagy.
Apoptosis↑,
TumAuto↑,
TumCG↓, these studies showed that the 2-DG, HK2 inhibitor, suppresses lung cancer cell growth in vivo.

2424-

2DG,

SRF,

The combination of the glycolysis inhibitor 2-DG and sorafenib can be effective against sorafenib-tolerant persister cancer cells

in-vitro,

HCC,

Hep3B

in-vitro,

HCC,

HUH7

ChemoSen↓, combination of 2-DG and sorafenib reduced persister tumor growth in mice
Glycolysis↓, The glycolysis inhibitor 2-Deoxy-D-glucose (2-DG), an inhibitor of all forms of HK
HK1↓,
HK2↓,
ATP↓, reducing ATP production

2433-

2DG,

Hexokinase inhibitor 2-deoxyglucose coordinates citrullination of vimentin and apoptosis of fibroblast-like synoviocytes by inhibiting HK2 /mTORC1-induced autophagy

in-vitro,

Arthritis,

in-vivo,

NA,

arthritis (AA) rat

Vim↓, 2-DG reduced cVIM and increased apoptosis by inhibiting autophagy of fibroblast-like synoviocytes.
HK2↓, 2-DG decreased HK2

2434-

2DG,

Inhibition of Key Glycolytic Enzyme Hexokinase 2 Ameliorates Psoriasiform Inflammation in vitro and in vivo

in-vitro,

PSA,

in-vivo,

PSA,

HK2↓, Two commonly used inhibitors, 2-Deoxy-D-glucose (2-DG) and 3-BrPA, have also been discovered
NF-kB↓,
NLRP3↓, Knockdown of HK in previous study inhibits activation of NLRP3 by extracellular ATP

1340-

3BP,

Safety and outcome of treatment of metastatic melanoma using 3-bromopyruvate: a concise literature review and case study

Review,

NA,

Glycolysis↓, inhibiting key glycolysis enzymes
HK2↓,
LDH↓,
OXPHOS↓, inhibits mitochondrial oxidative phosphorylation
angioG↓,
H2O2↑, induces hydrogen peroxide generation in cancer cells (oxidative stress effect)
eff↑, Concurrent use of a GSH depletor(paracetamol) with 3BP killed resistant melanoma cells

5271-

3BP,

The anticancer agent 3-bromopyruvate: a simple but powerful molecule taken from the lab to the bedside

Review,

Var,

selectivity↑, 3-bromopyruvate (3BP), a simple alkylating chemical compound was presented to the scientific community as a potent anticancer agent, able to cause rapid toxicity to cancer cells without bystander effects on normal tissues.
selectivity↑, results obtained in cancer research with this small molecule have contradicted the just noted general fear. Indeed, a promising drug has been revealed with an effective mechanism of action and an outstanding selectivity towards cancer cells
ATP↓, once inside cancer cells 3BP can then inhibit both of their energy (ATP) producing systems, i.e., glycolysis, likely by inhibiting hexokinase-2 (hk-2) and mitochondrial oxidative phosphorylation
Glycolysis↓,
HK2↓,
mt-OXPHOS↓,
GAPDH↓, Different reports have shown that 3BP is able to inhibit GAPDH activity leading to the loss of the ATP-producing steps that occur downstream of this enzyme
mtDam↑, Mitochondria related cell death has also been reported following 3BP treatment.
GSH↓, Ehrke and co-workers have demonstrated that 3BP inhibits glycolysis and deplete the glutathione levels in primary rat astrocytes
ROS↑, Others have also observed an increase in ROS levels following 3BP treatment that induces endoplasmic reticulum stress
ER Stress↑,
TumAuto↑, Autophagy has been associated with 3BP activity in breast cancer cell lines (Zhang et al., 2014),
LC3‑Ⅱ/LC3‑Ⅰ↑, 3BP leads to aggressive autophagy involving a decrease in the ratio of LC3I/LC3II and the levels of p62 as well as dephosphorylation of Akt and p53.
p62↓,
Akt↓,
HDAC↓, 3BP’s, it has been reported to be involved in suppressing epigenetic events as it inhibits histone deacetylase (HDAC) isoforms 1 and 3 in MCF-7 breast cancer cells leading to apoptosis
TumCA↑, Proliferation inhibition by 3BP treatment has also been related with the induction of S-phase and G2/M- phase arrest (Liu et al. 2009)
Bcl-2↓, downregulation of the expression of Bcl-2, c-Myc and mutant p53, the upregulation of Bax, activation of caspase-3 and mitochondrial leakage of cytochrome c
cMyc↓,
Casp3↑,
Cyt‑c↑,
Mcl-1↓, mitochondria mediated apoptosis triggered by 3BP was found to be associated with the downregulation of Mcl-1 through the phosphoinositide-3-kinase/Akt pathway (Liu et al. 2014).
PARP↓, 3BP treatment decreases the levels of poly(ADP-ribose) polymerase (PARP) and cleaved PARP.
ChemoSen↑, it might be a good adjuvant for commonly used chemotherapy agents, or a replacement for such agents.

5280-

3BP,

Anticancer Efficacy of the Metabolic Blocker 3-Bromopyruvate: Specific Molecular Targeting

in-vitro,

PC,

mtDam↑, 3-BromoPyruvate severely damaged mitochondrial integrity which might have severely affected ATP generation in cancer cells.
HK2↓, 3-BP inhibits hexokinase II (HK2) and TGFbeta1 and enhanced active caspase-3 expression in tumor tissues as compared to untreated control.
TGF-β↓,
Casp3↑,
selectivity↑,

5279-

3BP,

Rad,

Abstract 5243: 3-Bromopyruvate in combination with radiation inhibits pancreatic cancer growth by dismantling mitochondria and ATP generation in a preclinical mouse model

in-vivo,

PC,

ATP↓, ATP production was severely inhibited in cancer cells treated with same concentration of 3-BP
HK2↓, It exerts potent anticancer effects by inhibiting hexokinase II enzyme of glycolysis pathway and ATP generation in cancer cells.
RadioS↑, We also observed that 3-BP in combination with low doses of irradiation was more effective in killing cancer cells than 3-BP alone.

5278-

3BP,

The effect of 3-bromopyruvate on human colorectal cancer cells is dependent on glucose concentration but not hexokinase II expression

in-vitro,

CRC,

HCT116

in-vitro,

CRC,

Caco-2

in-vitro,

CRC,

SW48

ATP↓, 3-Bromopyruvate (3BP) is a pyruvate analogue with alkylating properties that depletes cellular ATP levels and induces rapid cell death in neoplastic cells with limited cytotoxic effects against normal cells.
TumCD↑,
selectivity↑,
toxicity↓, 3BP treatment led to eradication of tumours of hepatocellular carcinoma cell origin in rats without apparent cytotoxic effects [19]
OS↑, first human case report suggested that 3BP was able to prolong survival in a cancer patient diagnosed with hepatocellular carcinoma in 2012 [19,20].
HK2?, 3BP is able to dissociate and inhibit mitochondrial HKII function, thereby reducing ATP production. 3BP binding also frees up binding sites previously occupied by HKII
Cyt‑c↑, llowing pro-apoptotic molecules (such as BAX and BAD) to promote the release of cytochrome c into the cytosol and induce eventual cell death
eff↑, Raji lymphoma cells grown under hypoxic conditions were more sensitive to 3BP than in normoxia
p‑Akt↑, 3BP induces rapid AKT phosphorylation at residue Thr-308

5277-

3BP,

3-Bromopyruvate inhibits pancreatic tumor growth by stalling glycolysis, and dismantling mitochondria in a syngeneic mouse model

in-vivo,

PC,

Panc02

mouse model

HK2↓, It exerts potent anticancer effects by inhibiting hexokinase II enzyme (HK2) of the glycolytic pathway in cancer cells while not affecting the normal cells.
selectivity↑, it doesn’t affect the normal cells but strongly toxic to cancer cells
ATP↓, 3-BP killed 95% of Panc-2 cells at 15 μM concentration and severely inhibited ATP production by disrupting the interaction between HK2 and mitochondrial Voltage Dependent Anion Channel-1 (VDAC1) protein.
mtDam↑, Electron microscopy data revealed that 3-BP severely damaged mitochondrial membrane in cancer cells.
Dose↝, We further examined therapeutic effect of 3-BP in syngeneic mouse pancreatic cancer model by treating animals with 10, 15 and 20 mg/kg dose. 3-BP at 15 & 20 mg/kg dose level significantly reduced tumor growth by approximately 75-80% in C57BL/6 female
TumCG↓, 3-BP inhibit in vivo pancreatic tumor growth in C57BL/6 mouse model
Casp3↑, observed enhanced expression of active caspase-3 in tumor tissues exhibited apoptotic death.
Glycolysis↓, Notably, metabolomic data also revealed severe inhibition in glycolysis, NADP, ATP and lactic acid production in cancer cells treated with 40 μM 3-BP.
NADPH↓,
ATP↓,
ROS↑, 3-BP treatment produces increased levels of reactive oxygen species (ROS), which causes DNA damage with reduction of free glutathione levels [11].
DNAdam↑,
GSH↓,
Bcl-2↓, Further, treatment with 40 µM of 3-BP suppressed BCL2L1 expression and causing activation of mitochondrial caspases
Casp↑,
lactateProd↓, Metabolic inhibition of glucose consumption and lactic acid production in cancer cells treated with 3-BP

5275-

3BP,

3-Bromopyruvate (3BP) a fast acting, promising, powerful, specific, and effective "small molecule" anti-cancer agent taken from labside to bedside: Introduction to a special issue

Review,

Var,

AntiCan↑, the subject of this mini-review series, is an incredibly powerful and swift acting anticancer agent.
HK2↓, reported that HK2 is constitutively overexpressed and that 3BP an inhibitor of this enzyme induces cell death.
OCR↓, this agent was found to inhibit the membrane potential, oxygen consumption, and dehydrogenase activities.

5272-

3BP,

The efficacy of the anticancer 3-bromopyruvate is potentiated by antimycin and menadione by unbalancing mitochondrial ROS production and disposal in U118 glioblastoma cells

in-vitro,

GBM,

U87MG

in-vitro,

Nor,

HEK293

Glycolysis↓, We used the antiglycolytic 3-bromopyruvate (3BP) as a metabolic modifier to treat U118 glioblastoma cell
ROS↑, ROS generated in mitochondria were enhanced at 30 μM 3BP, possibly by unbalancing their generation and their disposal because of glutathione peroxidase inhibition.
GPx↓,
eff↓, Indeed, the scavenger of mitochondrial superoxide MitoTEMPO counteracted 3BP-induced cyt c release and weakened the potentiating effect of 3BP/
OXPHOS↓, (3BP) is a reactive non-specific drug that can act as a metabolic modifier by interfering with glycolysis and oxidative phosphorylation in cancer cells
HK2↓, The mitochondrial hexokinase-II is the main target since its activity is specifically blocked by the formation of a pyruvinyl adduct after reacting with 3BP at the surface of the outer mitochondrial membrane
ATP↓, In malignant tumour cell lines, 3BP inhibits ATPase activity, reduces ATP levels, and reverses chemoresistance by antagonizing drug efflux by acting on the ATP-binding cassette transporters (
ROS↑, Furthermore, 3BP increases the production of reactive oxygen species (ROS) (Ihrlund et al., 2008; Kim et al., 2008; Macchioni et al., 2011a), induces ER stress,
ER Stress↑,
BioAv↓, Unfortunately, prolonged treatment with the drug reduces ROS levels and confers resistance by inducing regulatory genes that act on antioxidant systems.
Cyt‑c↑, 3BP induces cytochrome c release without triggering an apoptotic cascade in U118 cells
eff↑, The ROS enhancers antimycin and menadione sensitize U118 cells to 3BP

5263-

3BP,

CET,

3-Bromopyruvate overcomes cetuximab resistance in human colorectal cancer cells by inducing autophagy-dependent ferroptosis

in-vitro,

CRC,

DLD1

NA,

HCT116

eff↑, Our results demonstrated that the co-treatment of 3-BP and cetuximab synergistically induced an antiproliferative effect in both CRC cell lines
Ferroptosis↓, co-treatment induced ferroptosis, autophagy, and apoptosis.
TumAuto↑,
Apoptosis↑,
FOXO3↑, co-treatment inhibited FOXO3a phosphorylation and degradation and activated the FOXO3a/AMPKα/pBeclin1 and FOXO3a/PUMA pathways, leading to the promotion of ferroptosis, autophagy, and apoptosis in DLD-1
AMPKα↑,
p‑Beclin-1↑,
HK2↓, 3-Bromopyruvate (3-BP), also known as hexokinase II inhibitor II, has shown promise as an anticancer agent against various types of cancer
ATP↓, 3-BP exerts its anticancer effects by manipulating cell energy metabolism and regulating oxidative stress, as evidenced by the accumulation of reactive oxygen species (ROS) [13,14,15,16].
ROS↑,
Dose↝, Eight days postinoculation, xenografted mice were randomly divided into four groups and intraperitoneally injected with PBS, 3-BP, cetuximab, or a combination of 3-BP and cetuximab every four days for five injections.
TumVol↓, 3-BP alone or co-treatment with 3-BP and cetuximab significantly reduced the tumor volume and tumor weight on Day 28, but co-treatment showed a greater reduction than 3-BP alone
TumW↓,
xCT↑, The protein level of SLC7A11 was significantly upregulated in all three cell lines following co-treatment (Fig. 2B).
GSH↓, co-treatment with 3-BP and cetuximab led to glutathione (GSH) depletion (Fig. 2D), reactive oxygen species (ROS) production
eff↓, Knockdown of either ATG5 or Beclin1 attenuated the cell death and MDA production induced by co-treatment
MDA↑,

5257-

3BP,

Tumor Energy Metabolism and Potential of 3-Bromopyruvate as an Inhibitor of Aerobic Glycolysis: Implications in Tumor Treatment

Review,

Var,

Glycolysis↓, In recent years, a small molecule alkylating agent, 3-bromopyruvate (3-BrPA), being an effective glycolytic inhibitor, has shown great potential as a promising antitumor drug.
mt-OXPHOS↓, Not only it targets glycolysis process, but also inhibits mitochondrial OXPHOS in tumor cells.
HK2↓, The direct inhibition of mitochondrial HK-II isolated from the rabbit liver implanted VX2 tumor via 3-BrPA was demonstrated by Ko et al. [17].
Cyt‑c↑, -BrPA treatment resulted in an increase of cytochrome c release [59,60], along with an elevated expression of active proapoptotic caspase-3 and a decrease of antiapoptotic Bcl-2 and Mcl-1 [59]
Casp3↓,
Bcl-2↓,
Mcl-1↓,
GAPDH↓, Additionally, GAPDH was found to be inhibited by 3-BrPA in several studies
LDH↓, Recent reports showed 3-BrPA had ability to inhibit post glycolysis targets and other metabolic pathways, such as LDH, PDH, TCA cycle, and glutaminolysis
PDH↓, 3-BrPA was proven to be an inhibitor of PDH [72,73,74],
TCA↓,
GlutaM↓, this inhibition of TCA cycle can lead to the impairment of glutaminolysis due to α-KG generated from glutamine is incorporated into the TCA cycle by IDH and αKD activities
GSH↓, Indeed, a remarkable decrease of reduced glutathione (GSH) level was observed after 3-BrPA treatment in both microorganisms and various tumor cells [53,61,65].
ATP↓, 3-BrPA successfully killed AS-30D hepatocellular carcinoma (HCC) cells via the inhibition of both ATP-producing glycolysis and mitochondrial respiration [17].
mitResp↓,
ROS↑, the increase of ROS and concomitant decrease of GSH were commonly found in 3-BrPA-mediated antitumor studies [53,59,61,64,65,76,77,86,89].
ChemoSen↑, When 3-BrPA was combined with cisplatin or oxaliplatin with non-toxic low-dose, 3-BrPA strikingly enhanced the antiproliferative effects of both platinum drugs in HCT116 cells and resistant p53-deficient HCT116 cells [89].
toxicity↝, Finally, two years after the first diagnosis, the patient died due to an overload of liver function rather than the tumor itself [118].

5269-

3BP,

The anti-metabolite KAT/3BP has in vitro and in vivo anti-tumor activity in lymphoma models.

in-vitro,

HCC,

toxicity↑, 3-Bromopyruvate (3BP), a small alkylating agent, acts as an anti-metabolite to vital substrates in cancer metabolism and exhibits antitumor activity across various cancer types, but the unformulated 3BP can cause high toxicity
eff↝, This study explores the efficacy of the 3BP clinical derivative KAT/3BP, currently in phase 1 for patients with hepatocellular carcinoma, in lymphoma models.
eff↑, AT/3BP exhibited synergistic activity when combined with lymphoma therapies, including bendamustine and R-CHOP.
Glycolysis↓, At acidic extracellular pH, 3BP enters cancer cells via monocarboxylic acid-1 (MCT-1) and inhibits glycolysis through hexokinase II (HK-2) covalent modification
HK2↓, with HK-2 inhibition and dissociation from mitochondria, apoptosis-inducing factor (AIF) release, and apoptosis induction (9).
AIF↑,
Apoptosis↑,
NK cell↑, In the latter, tumor growth was in vivo reversed, with an increase in the number of circulating CD4+, CD8+, and NK- cells
toxicity↑, unformulated 3BP administrations are associated with severe toxicities, including deaths (22,23)
toxicity↓, However, improvements have been made in developing novel 3BP formulations based on liposomes, polyethylene glycol (PEG), PEGylated liposomes (stealth liposomes), perillyl alcohol formulations, and others (12,22,24
Dose↝, KAT-101 and KAT-201 are two clinical 3BP derivatives formulated for oral or intratumoral (IT) administration, respectively (National Cancer Institute Thesaurus Codes C193479 and C193479), now entering the early clinical evaluation of patients with h
AntiTum↑, KAT/3BP has in vivo antitumor activity in a syngeneic mouse model.

5265-

3BP,

KAT/3BP: A Metabolism-Targeting Agent with Single and Combination Activity in Aggressive B-Cell Lymphomas

Review,

lymphoma,

Glycolysis↓, Under acidic extracellular pH, 3BP is transported into cancer cells via monocarboxylate transporter 1 (MCT1), inhibiting glycolysis by covalently modifying hexokinase II (HK2).
HK2↓, HK2 dissociation from mitochondria, release of apoptosis-inducing factor (AIF), and induction of apoptosis
AIF↓,
Apoptosis↑,
NK cell↑, In the latter, tumor regression was accompanied by increased circulating CD4+, CD8+, and NK cells, enhanced tumor-associated macrophage infiltration, and reduced local immunosuppression

5266-

3BP,

3-bromopyruvate-based agent KAT-101

Review,

Var,

eff↑, Upon oral administration of 3-BP-based agent KAT-101, the 3-BP derivative, being structurally similar to lactic acid, specifically binds to and enters cancer cells through monocarboxylic acid transporters (MCTs)
Glycolysis↓, KAT-101 interferes with both glycolysis and mitochondrial oxidative phosphorylation (OxPhos), thereby depleting adenosine triphosphate (ATP) levels and thus limits energy supply needed by cancer cells to proliferate.
OXPHOS↓,
ATP↓,
TumCP↓,
Apoptosis↑, This induces cancer cell apoptosis and prevents cancer cell proliferation.
HK2↓, In addition, KAT-101 is able to release mitochondrial-bound hexokinase (HK) II (HK2)
MPT↑, increases the formation of mitochondrial permeability transition pores (MPTPs), which induces apoptosis.
LDH↓, KAT-101 also inhibits a variety of enzymes, including lactate dehydrogenase (LDH), pyruvate dehydrogenase (PDH) and pyruvate dehydrogenase kinase (PDHK).
PDH↓,

5267-

3BP,

Targeting Energy Metabolism in Cancer Treatment

Review,

Var,

HK2↓, Two HK2 inhibitors have been identified, 2-deoxyglucose (2-DG) and 3-bromopyruvate (3-BP).

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↓,

938-

Api,

doxoR,

Apigenin and hesperidin augment the toxic effect of doxorubicin against HepG2 cells

vitro+vivo,

HCC,

HepG2

LDHA↓, 5x
HK2↓, 5x

206-

Api,

Inhibition of glutamine utilization sensitizes lung cancer cells to apigenin-induced apoptosis resulting from metabolic and oxidative stress

in-vitro,

Lung,

H1299

 20 uM

in-vitro,

Lung,

H460

in-vitro,

Lung,

A549

 40 uM

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

2324-

ART/DHA,

Research Progress of Warburg Effect in Hepatocellular Carcinoma

Review,

Var,

PKM2↓, DHA effectively suppressed aerobic glycolysis and ESCC progression by downregulating PKM2 expression in esophageal squamous cell carcinoma (ESCC) and ESCC cells
GLUT1↓, DHA inhibited leukemia cell K562 proliferation by suppressing GLUT1 and PKM2 levels, thereby regulating glucose uptake and inhibiting aerobic glycolysis
Glycolysis↓,
Akt↓, In LNCaP cells, DHA reduced Akt/mTOR and HIF-1α activity, leading to decreased expression of GLUT1, HK2, PKM2, and LDH and subsequent inhibition of aerobic glycolysis
mTOR↓,
Hif1a↓,
HK2↓,
LDH↓,
NF-kB↓, DHA was also found to inhibit the NF-κB signaling pathway to prevent GLUT1 translocation to the plasma membrane, thereby inhibiting the progression of non-small-cell lung cancer (NSCLC) cells via targeting glucose metabolism

2388-

Ash,

Withaferin A decreases glycolytic reprogramming in breast cancer

in-vitro,

BC,

MDA-MB-231

5 μM WA

in-vitro,

BC,

MDA-MB-468

in-vitro,

BC,

MCF-7

in-vitro,

BC,

MDA-MB-453

GlucoseCon↓, WA decreases the glucose uptake, lactate production and ATP generation by inhibiting the expression of key glycolytic enzymes i.e., GLUT1, HK2 and PKM2.
lactateProd↓,
ATP↓,
Glycolysis↓,
GLUT1↓,
HK2↓,
PKM2↓,
cMyc↓, WA decreases the protein expression of key glycolytic enzymes via downregulation of c-myc expression
Warburg↓, WA decreases protein expression of key glycolytic enzymes and Warburg effect via c-myc inhibition
cMyc↓,

2620-

Ba,

Natural compounds targeting glycolysis as promising therapeutics for gastric cancer: A review

Review,

GC,

Hif1a↓, Baicalein reduces the levels of HIF-1α in AGS gastric cancer cells in a dose-dependent manner (10, 20, and 40 µM)
HK2↓, down-regulates the levels of HK2, LDHA, and PDK1
LDHA↓,
PDK1↓,
p‑Akt↓, inhibits Akt phosphorylation under hypoxic conditions
PTEN↑, promotes the expression of PTEN protein
GlucoseCon↓, gradually restores glucose uptake and lactic acid production in hypoxic AGS cells to those observed under normoxic conditions
lactateProd↓,
Glycolysis↓, Baicalein and other compounds could directly regulate glycolysis-related enzymes

2617-

Ba,

Potential of baicalein in the prevention and treatment of cancer: A scientometric analyses based review

Review,

Var,

Ca+2↑, MDA-MB-231 ↑Ca2+
MMP2↓, MDA-MB-231 ↓MMP-2/9
MMP9↓,
Vim↓, ↓Vimentin, ↓SNAIL, ↑E-cadherin, ↓Wnt1, ↓β-catenin
Snail↓,
E-cadherin↑,
Wnt↓,
β-catenin/ZEB1↓,
p‑Akt↓, MCF-7 ↓p-Akt, ↓p-mTOR, ↓NF-κB
p‑mTOR↓,
NF-kB↓,
i-ROS↑, MCF-7 ↑Intracellular ROS, ↓Bcl-2, ↑Bax, ↑cytochrome c, ↑caspase-3/9
Bcl-2↓,
BAX↑,
Cyt‑c↑,
Casp3↑,
Casp9↑,
STAT3↓, 4T1, MDA-MB-231 ↓STAT3, ↓ IL-6
IL6↓,
MMP2↓, HeLa ↓MMP-2, ↓MMP-9
MMP9↓,
NOTCH↓, ↓Notch 1
PPARγ↓, ↓PPARγ
p‑NRF2↓, HCT-116 ↓p-Nrf2
HK2↓, ↓HK2, ↓LDH-A, ↓PDK1, ↓glycolysis, PTEN/Akt/HIF-1α regulation
LDHA↓,
PDK1↓,
Glycolysis↓,
PTEN↑, Furthermore, baicalein inhibited hypoxia-induced Akt phosphorylation by promoting PTEN accumulation, thereby attenuating hypoxia-inducible factor-alpha ( HIF-1a) expression in AGS cells.
Akt↓,
Hif1a↓,
MMP↓, SGC-7901 ↓ΔΨm
VEGF↓, ↓VEGF, ↓VEGFR2
VEGFR2↓,
TOP2↓, ↓Topoisomerase II
uPA↓, ↓u-PA, ↓TIMP1, ↓TIMP2
TIMP1↓,
TIMP2↓,
cMyc↓, ↓β-catenin, ↓c-Myc, ↓cyclin D1, ↓Axin-2
TrxR↓, EL4 ↓Thioredoxin reductase, ↑ASK1,
ASK1↑,
Vim↓, ↓vimentin
ZO-1↑, ↑ZO-1
E-cadherin↑, ↑E-cadherin
SOX2↓, PANC-1, BxPC-3, SW1990 ↓Sox-2, ↓Oct-4, ↓SHH, ↓SMO, ↓Gli-2
OCT4↓,
Shh↓,
Smo↓,
Gli1↓,
N-cadherin↓, ↓N-cadherin
XIAP↓, ↓XIAP

2616-

Ba,

The Role of HK2 in Tumorigenesis and Development: Potential for Targeted Therapy with Natural Products

Review,

Var,

Glycolysis↓, Related experiments have found that baicalein, the aglycone of baicalein inhibited hypoxia-enhanced glycolytic flux in AGS cells
HK2↓, and reduced the expression of key glycolytic-related enzymes such as HK2, lactate dehydrogenase A (LDH-A) and pyruvate dehydrogenase lipoamide kinase isozyme 1 (PDK1)
LDHA↓,
PDK1↓,
PTEN↑, Baicalein can also inhibit hypoxia-induced AKT phosphorylation by enhancing PTEN accumulation

2293-

Ba,

Baicalein suppresses inflammation and attenuates acute lung injury by inhibiting glycolysis via HIF‑1α signaling

in-vitro,

Nor,

MH-S

40, 20 and 10 µM

present study aimed to investigate the effects of baicalein on lung injury and inflammation

in-vivo,

NA,

30 male C57BL/6 mice

*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↓,

2295-

Ba,

5-FU,

Baicalein reverses hypoxia-induced 5-FU resistance in gastric cancer AGS cells through suppression of glycolysis and the PTEN/Akt/HIF-1α signaling pathway

in-vitro,

GC,

AGS

ChemoSen↑, baicalein increased the sensitivity of AGS cells to 5-FU treatment under hypoxia
HK2↓, hypoxia-enhanced glycolytic flux and expression of several critical glycolysis-associated enzymes (HK2, LDH-A and PDK1) in the AGS cells were suppressed by baicalein
LDHA↓,
PDK1↓,
Akt↓, baicalein inhibited hypoxia-induced Akt phosphorylation by promoting PTEN accumulation, thereby attenuating hypoxia-inducible factor-1α (HIF-1α) expression in AGS cells
PTEN↑,
Hif1a↓,
Glycolysis↓, results together suggest that inhibition of glycolysis via regulation of the PTEN/Akt/HIF-1α signaling pathway may be one of the mechanisms whereby baicalein reverses 5-FU resistance in cancer cells under hypoxia.
ROS↑, Taniguchi et al found that baicalein overcomes tumor necrosis factor-related apoptosis-inducing ligand resistance in cancer cells through DR5 upregulation mediated by ROS induction and CHOP/GADD153 activation
CHOP↑,

2298-

Ba,

Flavonoids Targeting HIF-1: Implications on Cancer Metabolism

Review,

Var,

TumCG↓, Baicalein significantly reduced intracerebral tumor growth and proliferation and promoted apoptosis and cell cycle arrest in orthotopic U87 gliomas in mice
TumCP↓,
Hif1a↓, suppression of HIF-1α by baicalein contributed to its reduction of cell viability in ovarian cancer (OVCAR-3 and CP-70) cell lines. 20-μM and 40-μM.
VEGF↓, Suppression of HIF-1α/VEGF pathway
ChemoSen↑, Moreover, baicalein increased the sensitivity of gastric cancer cells (AGS) to 5-fluorouracil (5-FU) under hypoxic conditions
Glycolysis↓, baicalein suppressed the expression of glycolysis-associated enzymes including HKII, PDK1, and LDHA via inhibition of Akt-phosphorylation, which led to HIF-1α suppression
HK2↓,
PDK1↓,
LDHA↓,
p‑Akt↓,
PTEN↑, Furthermore, baicalein inhibited hypoxia-induced Akt phosphorylation by promoting PTEN accumulation, thereby attenuating hypoxia-inducible factor-alpha ( HIF-1a) expression in AGS cells. (orginal paper)

2291-

Ba,

BA,

Baicalein and Baicalin Promote Melanoma Apoptosis and Senescence via Metabolic Inhibition

in-vitro,

Melanoma,

SK-MEL-28

0-40uM

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

2389-

BA,

Baicalin alleviates lipid accumulation in adipocytes via inducing metabolic reprogramming and targeting Adenosine A1 receptor

in-vitro,

Obesity,

3T3

*ECAR↑, Baicalin promoted metabolic reprogramming in 3T3-L1 preadipocytes, characterized by increased ECAR and decreased OCR
*OCR↓,
*p‑AMPK↑, baicalin significantly altered cellular respiration by reducing mitochondrial oxygen consumption while enhancing glycolytic flux, accompanied by increased phosphorylation of AMPK and ACC, suggesting an adaptation to altered energy availability.
*p‑ACC↑,
*Glycolysis↑, significant enrichment in metabolic pathways such as glycolysis, gluconeogenesis, and lipid metabolism.
*lipidDe↓, inhibited the maturation of sterol regulatory element binding protein 1 (SREBP1) and finally alleviated lipid deposition.
*SREBP1↓,
*FAO↑, baicalin induces metabolic reprogramming of adipocytes by inhibiting glucose aerobic metabolism while enhancing anaerobic glycolysis and FAO.
*HK2↑, baicalin upregulated glycolytic enzymes, such as HK1, HK2, PKM2, and LDHA, while downregulating pyruvate dehydrogenase,
*PKM2↑,
*LDHA↑,
*PDKs↓,
*ACC↓, leading to decreased acetyl-CoA production and enhanced fatty acid β-oxidation.

2708-

BBR,

Berberine decelerates glucose metabolism via suppression of mTOR‑dependent HIF‑1α protein synthesis in colon cancer cells

in-vitro,

CRC,

HCT116

 0, 6.25, 12.5, 25, 50 and 100 µM of berberine for 24 or 15 h

TumCG↓, we revealed that berberine, which suppressed the growth of colon cancer cell lines HCT116 and KM12C, greatly inhibited the glucose uptake and the transcription of glucose metabolic genes, GLUT1, LDHA and HK2 in these two cell lines
GlucoseCon↓,
GLUT1↓,
LDHA↓, berberine inhibited the mRNA levels of LDHA and HK2 in a concentration-dependent manner
HK2↓,
Hif1a↓, protein expression but not mRNA transcription of HIF‑1α, a well‑known transcription factor critical for dysregulated cancer cell glucose metabolism, was dramatically inhibited in berberine‑treated colon cancer cell lines
mTOR↓, mTOR signaling previously reported to regulate HIF‑1α protein synthesis was further found to be suppressed by berberine.
Glycolysis↓, berberine inhibits overactive glucose metabolism of colon cancer cells via suppressing mTOR‑depended HIF‑1α protein synthesis

2709-

BBR,

Berberine inhibits the glycolysis and proliferation of hepatocellular carcinoma cells by down-regulating HIF-1α

in-vitro,

HCC,

HepG2

0, 50, 100, or 200 μmol/

TumCP↓, After exposure to 100 μmol/L BBR, the proliferation, migration and invasion of HepG2 cells were reduced, along with apoptosis was increased, while the levels of glycolysis-related proteins were decreased
TumCMig↓,
TumCI↓,
Apoptosis↑,
Glycolysis↓, BBR inhibits proliferation and glycolysis of HCC cells in vivo
Hif1a↓, BBR can down-regulate HIF-1α in the hypoxic microenvironment, and hinder the proliferation and metastasis of breast cancer cell
GLUT1↓, treatment with 100μmol/L BBR for 48 h, the levels of GLUT1, HK2, PKM2, and LDHA mRNA were markedly reduced in HepG2 cells
HK2↓,
PKM2↓,
LDHA↓,

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↓,

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

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

1261-

CAP,

Capsaicin inhibits glycolysis in esophageal squamous cell carcinoma by regulating hexokinase‑2 expression

in-vitro,

ESCC,

KYSE150

GlucoseCon↓,
lactateProd↓,
HK2↓,
Glycolysis↓,
PTEN↑,
AKT1↓, RAC‑α serine threonine‑protein kinase signaling pathway was downregulated

2398-

CGA,

Polyphenol-rich diet mediates interplay between macrophage-neutrophil and gut microbiota to alleviate intestinal inflammation

in-vivo,

Col,

Mice with or without depletion of macrophages were administered with four individual phenolic acids including chlorogenic, ferulic, caffeic, and ellagic acids,

PKM2↓, Chlorogenic acid mitigated colitis by reducing M1 macrophage polarization through suppression of pyruvate kinase M 2 (Pkm2)-dependent glycolysis and inhibition of NOD-like receptor protein 3 (Nlrp3) activation
Glycolysis↓,
NLRP3↓,
Inflam↓, Anti-inflammatory effect of chlorogenic acid is mediated through PKM2-dependent glycolysis
HK2↓, hexokinase 2 (Hk2), pyruvate dehydrogenase kinase 1 (Pdk1) and lactate dehydrogenase A (Ldha), while CGA significantly decreased this up-regulated genes level in macrophages
PDK1↓,
LDHA↓,
GLUT1↓, significant reduction in the LPS-induced increased glucose transporter protein 1 (Glut1) mRNA
ECAR↓, Importantly, the enhanced extracellular acidification rates (ECRA), indicative of glycolysis, was rescued by CGA treatment

1143-

CHr,

Chrysin inhibited tumor glycolysis and induced apoptosis in hepatocellular carcinoma by targeting hexokinase-2

in-vitro,

HCC,

HepG2

0-60uM

in-vivo,

NA,

mouse

in-vitro,

HCC,

HepG3

in-vitro,

HCC,

HUH7

HK2↓,
GlucoseCon↓,
lactateProd↓,
Glycolysis↓,
Apoptosis↑,

2782-

CHr,

Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives

Review,

Var,

Review,

Stroke,

Review,

Park,

*antiOx↑, antioxidant, anti-inflammatory, hepatoprotective, neuroprotective
*Inflam↓, inhibitory effect of chrysin on inflammation and oxidative stress is also important in Parkinson’s disease
*hepatoP↑,
*neuroP↑,
*BioAv↓, Accumulating data demonstrates that poor absorption, rapid metabolism, and systemic elimination are responsible for poor bioavailability of chrysin in humans that, subsequently, restrict its therapeutic effects
*cardioP↑, cardioprotective [69], lipid-lowering effect [70]
*lipidLev↓,
*RenoP↑, Renoprotective
*TNF-α↓, chrysin reduces levels of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2).
*IL2↓,
*PI3K↓, induction of the PI3K/Akt signaling pathway by chrysin contributes to a reduction in oxidative stress and inflammation during cerebral I/R injury
*Akt↓,
*ROS↓,
*cognitive↑, Chrysin (25, 50, and 100 mg/kg) improves cognitive capacity, inflammation, and apoptosis to ameliorate traumatic brain injury
eff↑, chrysin and silibinin is beneficial in suppressing breast cancer malignancy via decreasing cancer proliferation
cycD1/CCND1↓, chrysin and silibinin induced cell cycle arrest via down-regulation of cyclin D1 and hTERT
hTERT/TERT↓,
VEGF↓, Administration of chrysin is associated with the disruption of hypoxia-induced VEGF gene expression
p‑STAT3↓, chrysin is capable of reducing STAT3 phosphorylation in hypoxic conditions without affecting the HIF-1α protein level.
TumMeta↓, chrysin is a potent agent in suppressing metastasis and proliferation of breast cancer cells during hypoxic conditions
TumCP↓,
eff↑, combination therapy of breast cancer cells using chrysin and metformin exerts a synergistic effect and is more efficient compared to chrysin alone
eff↑, combination of quercetin and chrysin reduced levels of pro-inflammatory factors, such as IL-1β, Il-6, TNF-α, and IL-10, via NF-κB down-regulation.
IL1β↓,
IL6↓,
NF-kB↓,
ROS↑, after chrysin administration, an increase occurs in levels of ROS that, subsequently, impairs the integrity of the mitochondrial membrane, leading to cytochrome C release and apoptosis induction
MMP↓,
Cyt‑c↑,
Apoptosis↑,
ER Stress↑, in addition to mitochondria, ER can also participate in apoptosis
Ca+2↑, Upon chrysin administration, an increase occurs in levels of ROS and cytoplasmic Ca2+ that mediate apoptosis induction in OC cells
TET1↑, In MKN45 cells, chrysin promotes the expression of TET1
Let-7↑, Chrysin is capable of promoting the expression of miR-9 and Let-7a as onco-suppressor factors in cancer to inhibit the proliferation of GC cells
Twist↓, Down-regulation of NF-κB, and subsequent decrease in Twist/EMT are mediated by chrysin administration, negatively affecting cervical cancer metastasis
EMT↓,
TumCCA↑, nduction of cell cycle arrest and apoptosis via up-regulation of caspase-3, caspase-9, and Bax are mediated by chrysin
Casp3↑,
Casp9↑,
BAX↑,
HK2↓, Chrysin administration (15, 30, and 60 mM) reduces the expression of HK-2 in hepatocellular carcinoma (HCC) cells to impair glucose uptake and lactate production.
GlucoseCon↓,
lactateProd↓,
Glycolysis↓, In addition to glycolysis metabolism impairment, the inhibitory effect of chrysin on HK-2 leads to apoptosis
SHP1↑, upstream modulator of STAT3 known as SHP-1 is up-regulated by chrysin
N-cadherin↓, Furthermore, N-cadherin and E-cadherin are respectively down-regulated and up-regulated upon chrysin administration in inhibiting melanoma invasion
E-cadherin↑,
UPR↑, chrysin substantially diminishes survival by ER stress induction via stimulating UPR, PERK, ATF4, and elF2α
PERK↑,
ATF4↑,
eIF2α↑,
RadioS↑, Irradiation combined with chrysin exerts a synergistic effect
NOTCH1↑, Irradiation combined with chrysin exerts a synergistic effect
NRF2↓, in reducing Nrf2 expression, chrysin down-regulates the expression of ERK and PI3K/Akt pathways—leading to an increase in the efficiency of doxorubicin in chemotherapy
BioAv↑, chrysin at the tumor site by polymeric nanoparticles leads to enhanced anti-tumor activity, due to enhanced cellular uptake
eff↑, Chrysin- and curcumin-loaded nanoparticles significantly promote the expression of TIMP-1 and TIMP-2 to exert a reduction in melanoma invasion

2784-

CHr,

Chrysin targets aberrant molecular signatures and pathways in carcinogenesis (Review)

Review,

Var,

Apoptosis↑, apoptosis, disrupting the cell cycle and inhibiting migration without generating toxicity or undesired side‑effects in normal cells
TumCMig↓,
*toxicity↝, toxic at higher doses and the recommended dose for chrysin is <3 g/day
ChemoSen↑, chrysin also inhibits multi‑drug resistant proteins and is effective in combination therapy
*BioAv↓, extremely low bioavailability in humans due to rapid quick metabolism, removal and restricted assimilation. The bioavailability of chrysin when taken orally has been estimated to be between 0.003 to 0.02%
Dose↝, safe and effective in various studies where volunteers have taken oral doses ranging from 300 to 625 mg without experiencing any documented effect
neuroP↑, Chrysin has been shown to exert neuroprotective effects via a variety of mechanisms, such as gamma-aminobutyric acid mimetic properties, monoamine oxidase inhibition, antioxidant, anti-inflammatory and anti-apoptotic activities
*P450↓, Chrysin inhibits cytochrome P450 2E1, alcohol dehydrogenase and xanthine oxidase at various dosages (20 and 40 mg/kg body weight) and protects Wistar rats against oxidative stress
*ROS↓,
*HDL↑, ncreased the levels of high-density lipoprotein cholesterol, glutathione S-transferase, superoxide dismutase and catalase
*GSTs↑,
*SOD↑,
*Catalase↑,
*MAPK↓, inactivate the MAPK/JNK pathway and suppress the NF-κB pathways, and at the same time upregulate the expression of PTEN, and activate the VEGF/AKT pathway
*NF-kB↓,
*PTEN↑,
*VEGF↑,
ROS↑, chrysin treatment in ovarian cancer led to the augmented generation of reactive oxygen species, a decrease in MMP and an increase in cytoplasmic Ca2+,
MMP↓,
Ca+2↑,
selectivity↑, It has been found that chrysin has no cytotoxic effect on normal cells, such as fibroblasts
PCNA↓, Chrysin likewise downregulates proliferating cell nuclear antigen (PCNA) expression in cervical carcinoma cells
Twist↓, Chrysin decreases the expression of TWIST 1 and NF-κB and thus suppresses epithelial-mesenchymal transition (EMT) in HeLa cells
EMT↓,
CDKN1C↑, Chrysin administration led to the upregulation of CDKN1 at the transcript and protein leve
p‑STAT3↑, Chrysin decreased the viability of 4T1 breast cancer cells by suppressing hypoxia-induced phosphorylation of STAT3
MMP2↓, chrysin-loaded PGLA/PEG nanoparticles modulated TIMPS and MMP2 and 9, and PI3K expression in a mouse 4T1 breast tumor model
MMP9↓,
eff↑, Chrysin used alone and as an adjuvant with metformin has been found to downregulate cyclin D and hTERT expression in the breast cancer cell line
cycD1/CCND1↓,
hTERT/TERT↓,
CLDN1↓, CLDN1 and CLDN11 expression have been found to be higher in human lung squamous cell carcinoma. Treatment with chrysin treatment reduces both the mRNA and protein expression of these claudin genes
TumVol↓, Treatment with chrysin treatment (1.3 mg/kg body weight) significantly decreases tumor volume, resulting in a 52.6% increase in mouse survival
OS↑,
COX2↓, Chrysin restores the cellular equilibrium of cells subjected to benzopyrene by downregulating the expression of elevated proteins, such as PCNA, NF-κB and COX-2
eff↑, quercetin and chrysin together decreased the levels of pro-inflammatory molecules, such as IL-6, -1 and -10, and the levels of TNF via the NF-κB pathway.
CDK2↓, Chrysin has been shown to inhibit squamous cell carcinoma via the modulation of Rb and by decreasing the expression of CDK2 and CDK4
CDK4↓,
selectivity↑, chrysin selectively exhibits toxicity and induces the self-programed death of human uveal melanoma cells (M17 and SP6.5) without having any effect on normal cells
TumCCA↑, halting the cell cycle at the G2/M or G1/S phases
E-cadherin↑, upregulation of E-cadherin and the downregulation of cadherin
HK2↓, Chrysin decreased expression of HK-2 in mitochondria, and the interaction between HK-2 and VDAC 2 was disrupted,
HDAC↓, Chrysin, a HDAC inhibitor, caused cytotoxicity, and also inhibited migration and invasion.

2785-

CHr,

Emerging cellular and molecular mechanisms underlying anticancer indications of chrysin

Review,

Var,

*NF-kB↓, suppressed pro-inflammatory cytokine expression and histamine release, downregulated nuclear factor kappa B (NF-kB), cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS)
*COX2↓,
*iNOS↓,
angioG↓, upregulated apoptotic pathways [28], inhibited angiogenesis [29] and metastasis formation
TOP1↓, suppressed DNA topoisomerases [31] and histone deacetylase [32], downregulated tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β)
HDAC↓,
TNF-α↓,
IL1β↓,
cardioP↑, promoted protective signaling pathways in the heart [34], kidney [35] and brain [8], decreased cholesterol level
RenoP↑,
neuroP↑,
LDL↓,
BioAv↑, bioavailability of chrysin in the oral route of administration was appraised to be 0.003–0.02% [55], the maximum plasma concentration—12–64 nM
eff↑, Chrysin alone and potentially in combination with metformin decreased cyclin D1 and hTERT gene expression in the T47D breast cancer cell line
cycD1/CCND1↓,
hTERT/TERT↓,
MMP-10↓, Chrysin pretreatment inhibited MMP-10 and Akt signaling pathways
Akt↓,
STAT3↓, Chrysin declined hypoxic survival, inhibited activation of STAT3, and reduced VEGF expression in hypoxic cancer cells
VEGF↓,
EGFR↓, chrysin to inhibit EGFR was reported in a breast cancer stem cell model [
Snail↓, chrysin downregulated MMP-10, reduced snail, slug, and vimentin expressions increased E-cadherin expression, and inhibited Akt signaling pathway in TNBC cells, proposing that chrysin possessed a reversal activity on EMT
Slug↓,
Vim↓,
E-cadherin↑,
eff↑, Fabrication of chrysin-attached to silver and gold nanoparticles crossbred reduced graphene oxide nanocomposites led to augmentation of the generation of ROS-induced apoptosis in breast cancer
TET1↑, Chrysin induced augmentation in TET1
ROS↑, Pretreatment with chrysin induced ROS formation, and consecutively, inhibited Akt phosphorylation and mTOR.
mTOR↓,
PPARα↓, Chrysin inhibited mRNA expression of PPARα
ER Stress↑, ROS production by chrysin was the critical mediator behind induction of ER stress, leading to JNK phosphorylation, intracellular Ca2+ release, and activation of the mitochondrial apoptosis pathway
Ca+2↑,
ERK↓, reduced protein expression of p-ERK/ERK
MMP↑, Chrysin pretreatment led to an increase in mitochondrial ROS creation, swelling in isolated mitochondria from hepatocytes, collapse in MMP, and release cytochrome c.
Cyt‑c↑,
Casp3↑, Chrysin could elevate caspase-3 activity in the HCC rats group
HK2↓, chrysin declined HK-2 combined with VDAC-1 on mitochondria
NRF2↓, chrysin inhibited the Nrf2 expression and its downstream genes comprising AKR1B10, HO-1, and MRP5 by quenching ERK and PI3K-Akt pathway
HO-1↓,
MMP2↓, Chrysin pretreatment also downregulated MMP2, MMP9, fibronectin, and snail expression
MMP9↓,
Fibronectin↓,
GRP78/BiP↑, chrysin induced GRP78 overexpression, spliced XBP-1, and eIF2-α phosphorylation
XBP-1↓,
p‑eIF2α↑,
*AST↓, Chrysin administration significantly reduced AST, ALT, ALP, LDH and γGT serum activities
ALAT↓,
ALP↓,
LDH↓,
COX2↑, chrysin attenuated COX-2 and NFkB p65 expression, and Bcl-xL and β-arrestin levels
Bcl-xL↓,
IL6↓, Reduction in IL-6 and TNF-α and augmentation in caspases-9 and 3 were observed due to chrysin supplementation.
PGE2↓, Chrysin induced entire suppression NF-kB, COX-2, PG-E2, iNOS as well.
iNOS↓,
DNAdam↑, Chrysin induced apoptosis of cells by causing DNA fragmentation and increasing the proportions of DU145 and PC-3 cells
UPR↑, Also, it induced ER stress via activation of UPR proteins comprising PERK, eIF2α, and GRP78 in DU145 and PC-3 cells.
Hif1a↓, Chrysin increased the ubiquitination and degradation of HIF-1α by increasing its prolyl hydroxylation
EMT↓, chrysin was effective in HeLa cell by inhibiting EMT and CSLC properties, NF-κBp65, and Twist1 expression
Twist↓,
lipid-P↑, Chrysin disrupted intracellular homeostasis by altering MMP, cytosolic Ca (2+) levels, ROS generation, and lipid peroxidation, which plays a role in the death of choriocarcinoma cells.
CLDN1↓, Chrysin decreased CLDN1 and CLDN11 expression in human lung SCC
PDK1↓, Chrysin alleviated p-Akt and inhibited PDK1 and Akt
IL10↓, Chrysin inhibited cytokines release, TNF-α, IL-1β, IL-10, and IL-6 induced by Ni in A549 cells.
TLR4↓, Chrysin suppressed TLR4 and Myd88 mRNA and protein expression.
NOTCH1↑, Chrysin inhibited tumor growth in ATC both in vitro and in vivo through inducing Notch1
PARP↑, Pretreating cells with chrysin increased cleaved PARP, cleaved caspase-3, and declined cyclin D1, Mcl-1, and XIAP.
Mcl-1↓,
XIAP↓,

2790-

CHr,

Chrysin: Pharmacological and therapeutic properties

Review,

Var,

*hepatoP↑, graphical abstract
*neuroP↓,
*ROS↓,
*cardioP↑,
*Inflam↓,
eff↑, suppression of hTERT and cyclin D1 gene expression in T47D breast cancer cell lines is due to the combined effect of metformin and chrysin
hTERT/TERT↓,
cycD1/CCND1↓,
MMP9↓, nanoparticle-based chrysin in C57B16 mice bearing B16F10 melanoma tumors was markedly presented reductions in the levels of MMP-9, MMP-2, and TERT genes, whereas it enhanced TIMP-2 andTIMP-1 genes expression
MMP2↓,
TIMP1↑,
TIMP2↑,
BioAv↑, nano-encapsulation of chrysin and curcumin improved the delivery of these phytochemicals that significantly inhibited the growth of cancer cells, while it decreased the hTERT gene expression via increased solubility and bioavailability
HK2↓, chrysin treatment restrained tumor growth in HCC xenograft models and significantly reduced HK-2 expression in tumor tissue
ROS↑, showing a significant increase in intracellular reactive oxygen species (ROS), cytotoxicity, mitochondrial membrane potential (MMP) collapse, caspase-3 activation, ADP/ATP ratio, and ultimately apoptosis
MMP↓,
Casp3↑,
ADP:ATP↑,
Apoptosis↑,
ER Stress↑, Likewise, chrysin encouraged endoplasmic reticulum (ER) stress via stimulation of unfolded protein response (UPR
UPR↑,
GRP78/BiP↝, (eIF2Î±), PRKR-like ER kinase (PERK) and 78 kDa glucose-regulated protein (GRP78).
eff↑, silibinin and chrysin synergistically inhibited growth of T47D BCC and downregulated the hTERT and cyclin D1 level
Ca+2↑, Primarily, increased ROS and cytoplasmic Ca 2+ levels alongside induction of cell death and loss of MMP are involved in inhibition of ovarian cancer through chrysin.

1274-

Cin,

Cinnamon bark extract suppresses metastatic dissemination of cancer cells through inhibition of glycolytic metabolism

vitro+vivo,

BC,

MDA-MB-231

TumCI↓, CBE decreased cell motility and invasion of MDA-MB-231 human breast cancer cells without affecting their cell viability
G6PD↓,
HK2↓,
Glycolysis↓, CBE suppresses metastatic dissemination of cancer cells through inhibition of glycolysis metabolism.

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.

1585-

Citrate,

Sodium citrate targeting Ca2+/CAMKK2 pathway exhibits anti-tumor activity through inducing apoptosis and ferroptosis in ovarian cancer

in-vitro,

Ovarian,

SKOV3

15.93 mM

in-vitro,

Ovarian,

A2780S

16.8 mM

in-vitro,

Nor,

HEK293

Apoptosis↑,
Ferroptosis↑,
Ca+2↓, Sodium citrate chelates intracellular Ca2+
CaMKII ↓, inhibits the CAMKK2/AKT/mTOR/HIF1α-dependent glycolysis pathway, thereby inducing cell apoptosis.
Akt↓,
mTOR↓,
Hif1a↓,
ROS↑, Inactivation of CAMKK2/AMPK pathway reduces Ca2+ level in the mitochondria by inhibiting the activity of the MCU, resulting in excessive ROS production.
ChemoSen↑, Sodium citrate increases the sensitivity of ovarian cancer cells to chemo-drugs
Casp3↑,
Casp9↑,
BAX↑,
Bcl-2↓,
Cyt‑c↑, co-localization of cytochrome c and Apaf-1
GlucoseCon↓, glucose consumption, lactate production and pyruvate content were significantly reduced
lactateProd↓,
Pyruv↓,
GLUT1↓, sodium citrate decreased both mRNA and protein expression levels of glycolysis-related proteins such as Glut1, HK2 and PFKP
HK2↓,
PFKP↓,
Glycolysis↓, sodium citrate inhibited glycolysis of SKOV3 and A2780 cells
Hif1a↓, HIF1α expression was decreased significantly after sodium citrate treatment
p‑Akt↓, phosphorylation of AKT and mTOR was notably suppressed after sodium citrate treatment.
p‑mTOR↓,
Iron↑, ovarian cancer cells treated with sodium citrate exhibited higher Fe2+ levels, LPO levels, MDA levels, ROS and mitochondrial H2O2 levels
lipid-P↑,
MDA↑,
ROS↑,
H2O2↑,
mtDam↑, shrunken mitochondria, an increase in mitochondrial membrane density and disruption of mitochondrial cristae
GSH↓, (GSH) levels, GPX activity and expression levels of GPX4 were significantly reduced in SKOV3 and A2780 cells with sodium citrate treatment
GPx↓,
GPx4↓,
NADPH/NADP+↓, significant elevation in the NADP+/NADPH ratio was observed with sodium citrate treatment
eff↓, Fer-1, NAC and NADPH significantly restored the cell viability inhibited by sodium citrate
FTH1↓, decreased expression of FTH1
LC3‑Ⅱ/LC3‑Ⅰ↑, sodium citrate increased the conversion of cytosolic LC3 (LC3-I) to the lipidated form of LC3 (LC3-II)
NCOA4↑, higher levels of NCOA4
eff↓, test whether Ca2+ supplementation could rescue sodium citrate-induced ferroptosis. The results showed that Ca2+ dramatically reversed the enhanced levels of MDA, LPO and ROS triggered by sodium citrate
TumCG↓, sodium citrate inhibited tumor growth by chelation of Ca2+ in vivo

1576-

Citrate,

Targeting citrate as a novel therapeutic strategy in cancer treatment

Review,

Var,

TCA↓, Citrate serves as a key metabolite in the tricarboxylic acid cycle (TCA cycle, also referred to as the Krebs cycle)
T-Cell↝, modulation of T cell differentiation
Glycolysis↓, Citrate directly suppresses both cell glycolysis and TCA.
PKM2↓, citrate also inhibits glycolysis via its indirect inhibition of PK
PFK2?, In addition, citrate can inhibit PFK2,
SDH↓, citrate can inhibit enzymes, such as succinate dehydrogenase (SDH) and pyruvate dehydrogenase (PDH), in the TCA cycle
PDH↓,
β-oxidation↓, Citrate also inhibits β-oxidation as it promotes the formation of malonyl-CoA, which decreases the mitochondrial transport of fatty acids by inhibiting carnitine palmitoyl transferase I (CPT I)
CPT1A↓,
FASN↑, citrate has a positive role in promoting fatty acid synthesis
Casp3↑,
Casp2↑,
Casp8↑,
Casp9↑,
cl‑PARP↑,
Hif1a↓, Notably, in AML cell line U937, citrate induces apoptosis in a dose- and time-dependent manner by regulating the expression of HIF-1Î± and its downstream target GLUT-1
GLUT1↓,
angioG↓, citrate can also inhibit angiogenesis
Ca+2↓, chelate calcium ions in tumor cells
ROS↓, The other potential mechanism involved in citrate-mediated promotion of cancer growth and proliferation may be through its ability to decrease the levels of reactive oxygen species (ROS) in tumor cells
eff↓, dual effects of citrate in tumors may depend on the concentrations of citrate treatment, and different concentrations may bring out completely opposite effects even in the same tumor.
Dose↓, citrate concentration (<5 mM) appears to boost tumor growth and expansion in lung cancer A549 cells. 10mM and higher inhibited cell growth.
eff↑, citrate combined with ultraviolet (UV) radiation caused activation of caspase-3 and -9 in tumor cells (
Mcl-1↓, citrate has also been found to downregulate Mcl-1
HK2↓, Citrate also inhibits the enzymes PFK1 and hexokinase II (HK II) in glycolysis in tumor cells
IGF-1R↓,
PTEN↑, citrate may exert its effect via activating PTEN pathway
citrate↓, In addition to prostate cancer, citrate levels are significantly decreased in blood of patients with lung, bladder, pancreas and esophagus cancers
Dose∅, daily oral administration of citrate for 7 weeks at dose of 4 g/kg/day reduces tumor growth of several xenograft tumors and increases significantly the numbers of tumor-infiltrating T cells with no significant side effects in mouse models
eff↑, combining citrate with other compounds such as celecoxib, cisplatin, and 3-bromo-pyruvate, and have generated promising results
eff↑, combination of low effective doses of 3-bromo-pyruvate (3BP) (15uM), an inhibitor of glycolysis, and citrate (3 mM) significantly depleted the proliferation capability and migratory power of the C6 glioma
eff↑, Zinc treatment could lead to citrate accumulation in malignant prostate cells, which could have therapeutic potential in clinical therapy of prostate cancer.
eff↑, synergistic efficacy mediated by citrate combined with current checkpoint blockade therapies with anti-CTLA4 and/or anti-PD1/PDL1 will develop alternative novel strategies for future immunotherapy.

Showing Research Papers: 1 to 50 of 139
Page 1 of 3 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 139

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 1, Catalase↑, 1, GSTs↑, 1, HDL↑, 1, lipidDe↓, 1, ROS↓, 3, SOD↑, 1,

Mitochondria & Bioenergetics ⓘ

OCR↓, 1,

Core Metabolism/Glycolysis ⓘ

ACC↓, 1, p‑ACC↑, 1, p‑AMPK↑, 1, ECAR↑, 1, FAO↑, 1, Glycolysis↓, 1, Glycolysis↑, 1, HK2↓, 1, HK2↑, 1, LDHA↑, 1, lipidLev↓, 1, PDKs↓, 1, PFK1↓, 1, PKM2↓, 1, PKM2↑, 1, SREBP1↓, 1,

Cell Death ⓘ

Akt↓, 1, iNOS↓, 1, MAPK↓, 1,

Proliferation, Differentiation & Cell State ⓘ

PI3K↓, 1, PTEN↑, 1,

Angiogenesis & Vasculature ⓘ

Hif1a↓, 1, VEGF↑, 1,

Immune & Inflammatory Signaling ⓘ

COX2↓, 1, IL2↓, 1, Inflam↓, 3, NF-kB↓, 2, TNF-α↓, 1,

Drug Metabolism & Resistance ⓘ

BioAv↓, 2, P450↓, 1,

Clinical Biomarkers ⓘ

AST↓, 1,

Functional Outcomes ⓘ

cardioP↑, 2, cognitive↑, 1, hepatoP↑, 2, neuroP↓, 1, neuroP↑, 1, RenoP↑, 1, toxicity↝, 1,
Total Targets: 46

Scientific Paper Hit Count for: HK2, Hexokinase 2

14 3-bromopyruvate
8 Quercetin
8 Propolis -bee glue
8 Sulforaphane (mainly Broccoli)
7 2-DeoxyGlucose
7 Baicalein
7 EGCG (Epigallocatechin Gallate)
7 Resveratrol
6 Metformin
5 Chrysin
5 Shikonin
4 Graviola
3 Berberine
3 Citric Acid
3 Curcumin
3 Ursolic acid
2 Apigenin (mainly Parsley)
2 Baicalin
2 Capsaicin
2 Chemotherapy
2 Magnetic Fields
2 Pachymic acid
2 Piperlongumine
2 Silymarin (Milk Thistle) silibinin
2 Vitamin C (Ascorbic Acid)
2 Vitamin D3
1 Sorafenib (brand name Nexavar)
1 Radiotherapy/Radiation
1 cetuximab
1 Alpha-Lipoic-Acid
1 doxorubicin
1 Artemisinin
1 Ashwagandha(Withaferin A)
1 5-fluorouracil
1 Betulinic acid
1 Caffeic acid
1 Chlorogenic acid
1 Cinnamon
1 diet FMD Fasting Mimicking Diet
1 diet Methionine-Restricted Diet
1 Piperine
1 Taurine
1 Emodin
1 flavonoids
1 Hydrogen Gas
1 Honokiol
1 Ivermectin
1 lambertianic acid
1 Licorice
1 Luteolin
1 Matrine
1 Oroxylin-A
1 Proanthocyanidins
1 Phenylbutyrate
1 Rosmarinic acid
1 Thymoquinone
1 triptolide
1 Vitamin K2
1 Wogonin
1 Worenine
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#:773  State#:%  Dir#:%
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HK2 Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Metal & Cofactor Biology ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

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 ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Proliferation, Differentiation & Cell State ⓘ

Angiogenesis & Vasculature ⓘ

Immune & Inflammatory Signaling ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

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