Warburg Cancer Research Results

Warburg, Warburg Effect: Click to Expand ⟱
Source:
Type: effect

The Warburg effect (aerobic glycolysis) is a metabolic phenotype where many cancer cells use high glycolytic flux and lactate production even when oxygen is available. Tumors often contain hypoxic regions that further drive glycolysis, but Warburg metabolism can also occur under normoxic conditions (“pseudo-hypoxia”) via oncogenic signaling and metabolic rewiring.

Hypoxia-inducible factor 1 alpha (HIF-1α) is one important driver in hypoxic tumor regions. HIF-1α upregulates glycolytic genes (e.g., GLUT1, HK2, LDHA) and promotes reduced mitochondrial pyruvate oxidation in part through induction of PDK (which inhibits PDH), shifting carbon toward lactate.

Warburg effect (GLUT1, LDHA, HK2, and PKM2).
Classic HIF-Warburg axis: PDK1 and MCT4 (SLC16A3) (pyruvate gate + lactate export).

Here are some of the key pathways and potential targets:

Note: use database Filter to find inhibitors: Ex pick target HIF1α, and effect direction ↓

1.Glycolysis Inhibitors:(2-DG, 3-BP)
- HK2 Inhibitors: such as 2-deoxyglucose, can reduce glycolysis
-PFK1 Inhibitors: such as PFK-158, can reduce glycolysis
-PFKFB Inhibitors:
- PKM2 Inhibitors: (Shikonin)
-Can reduce glycolysis
- LDH Inhibitors: (Gossypol, FX11)
-Reducing the conversion of pyruvate to lactate.
-Inhibiting the production of ATP and NADH.
- GLUT1 Inhibitors: (phloretin, WZB117)
-A key transporter involved in glucose uptake.
-GLUT3 Inhibitors:
- PDK1 Inhibitors: (dichloroacetate)
- A key enzyme involved in the regulation of glycolysis. PDK inhibitors (e.g., DCA) activate PDH and shift pyruvate into TCA/OXPHOS, reducing lactate pressure.

2.Pentose phosphate pathway:
- G6PD Inhibitors: can reduce the pentose phosphate pathway

3.Hypoxia-inducible factor 1 alpha (HIF1α) pathway:
- HIF1α inhibitors: (PX-478,Shikonin)
-Reduce expression of glycolytic genes and inhibit cancer cell growth.

4.AMP-activated protein kinase (AMPK) pathway:
-AMPK activators: (metformin,AICAR,berberine)
-Can increase AMPK activity and inhibit cancer cell growth.

5.mTOR pathway:
- mTOR inhibitors:(rapamycin,everolimus)
-Can reduce mTOR activity and inhibit cancer cell growth.

Warburg Targeting Matrix (Cancer Metabolism)

Node What It Does (Warburg role) Representative Inhibitors / Modulators Mechanism Snapshot Typical Tumor Effects Best-Fit Tumor Context Common Constraints / Gotchas TSF Combination Logic
GLUT (glucose uptake)
GLUT1 (SLC2A1) focus		 Controls glucose entry; sets the upper bound on glycolytic flux. Research/repurposing: WZB117 (GLUT1), BAY-876 (GLUT1), STF-31 (GLUT1 tool), Fasentin (GLUT), Phloretin (broad, weak)
Dietary/indirect: some polyphenols reported to lower GLUT1 expression (context) 		Blocks glucose transport or reduces GLUT1 expression → less substrate for glycolysis & PPP. ATP stress (in highly glycolytic tumors), lactate ↓, growth slowdown; can sensitize to stressors. High-GLUT1 tumors; hypoxic / glycolysis-addicted phenotypes. Systemic glucose handling and glucose-dependent tissues; tumor compensation via alternate fuels. P, R Pairs with ROS/ETC stressors or LDH/MCT blockade; beware compensatory glutaminolysis/fatty acid oxidation.
Hexokinase (HK2)
first committed glycolysis step		 Traps glucose as G-6-P; HK2 often upregulated and mitochondria-associated in tumors. Clinical/adjunct interest: 2-Deoxyglucose (2-DG; glycolysis + glycosylation stress)
Research: Lonidamine-class glycolysis axis drugs (not “pure HK2”), 3-bromopyruvate (hazardous research agent; not for casual use) 		Competitive substrate mimic (2-DG) → 2-DG-6P accumulation; HK flux ↓; ER glycosylation stress ↑. ATP ↓, AMPK ↑, ER stress/UPR ↑, autophagy ↑, apoptosis (context); radiosensitization reported. Highly glycolytic tumors; tumors with strong HK2 dependence; hypoxic cores. Normal glucose-dependent tissues; ER-stress toxicities; dosing/tolerability limits in practice. P, R, G Pairs with radiation, pro-oxidant stress, or MCT/LDH blockade; watch systemic glucose effects.
LDH (LDHA/LDHB)
pyruvate ⇄ lactate		 Regenerates NAD+ to sustain glycolysis; LDHA supports lactate production and acidification. Tier A direct inhibitors: FX11, (R)-GNE-140, NCI-006, Oxamate, Galloflavin, Gossypol
Tier B indirect: polyphenols (often lactate/LDH expression ↓ rather than catalytic inhibition) 		Blocks LDH catalysis → NAD+ recycling ↓ → glycolysis throttles; pyruvate handling shifts; redox pressure ↑. Lactate ↓, glycolytic flux ↓, oxidative stress ↑ (often secondary), growth inhibition; immune microenvironment may improve if lactate decreases. LDHA-high tumors; lactate-driven immunosuppression; glycolysis-addicted phenotypes. Metabolic plasticity: tumors switch fuels; some LDH inhibitors have PK liabilities; “LDH release” ≠ LDH inhibition. R, G Pairs with MCT inhibition (trap lactate), NAD+ axis inhibitors, immune therapy (lactate suppression logic), and OXPHOS stressors (context).
MCT (lactate transport)
MCT1 (SLC16A1), MCT4 (SLC16A3)		 Exports lactate + H+ (acidifies TME); enables lactate shuttling between tumor subclones. Clinical-stage: AZD3965 (MCT1 inhibitor; clinical trials)
Research: AR-C155858 (MCT1/2), Syrosingopine (MCT1/4; repurposed), Lonidamine (MCT + MPC axis) 		Blocks lactate export/import → intracellular acid stress ↑ (in glycolytic cells) and lactate shuttling ↓. Acid stress, growth inhibition; may improve immune function by reducing lactate/acidic suppression (context). MCT1-high tumors; oxidative “lactate-using” tumor fractions; tumors with lactate shuttling. MCT4-driven export can bypass MCT1-only inhibitors; hypoxia upregulates MCT4; need target matching. P, R Pairs strongly with LDH inhibitors (cut production + block export), and with immune therapy rationale (lactate/acid microenvironment).
PDK (PDK1-4)
PDH gatekeeper		 PDK inhibits PDH → keeps pyruvate out of mitochondria; supports Warburg by favoring lactate. Prototype: Dichloroacetate (DCA; pan-PDK inhibitor “classic”)
Research: AZD7545 (PDK2 inhibitor; tool), newer PDK inhibitor series (research) 		Inhibits PDK → PDH active ↑ → pyruvate into TCA/OXPHOS ↑; lactate pressure ↓. Warburg reversal pressure (context), lactate ↓, mitochondrial flux ↑; can increase ROS in some settings (secondary). PDK-high tumors; tumors with suppressed PDH flux; “glycolysis locked” metabolic phenotype. Requires functional mitochondrial capacity; hypoxia can limit OXPHOS shift; effect is often modulatory rather than directly cytotoxic. R, G Pairs with therapies that exploit mitochondrial dependence or redox stress; can complement LDH/MCT strategies by reducing lactate drive.

Time-Scale Flag (TSF): P / R / G

  • P: 0–30 min (direct transport/enzyme flux effects begin)
  • R: 30 min–3 hr (acute ATP/NAD+/acid stress and signaling changes)
  • G: >3 hr (gene adaptation, phenotype outcomes, immune/TME effects)
Scientific Papers found: Click to Expand⟱
5273- 3BP,    The promising anticancer drug 3-bromopyruvate is metabolized through glutathione conjugation which affects chemoresistance and clinical practice: An evidence-based view
- Review, Var, NA
AntiCan↑, 3BP exhibited strong anticancer effects in both preclinical and human studies e.g. energy depletion, oxidative stress, anti-angiogenesis, anti-metastatic effects, targeting cancer stem cells and antagonizing the Warburg effect.
ROS↑,
angioG↓,
CSCs↓,
Warburg↓,
GSH↓, Reported decrease in endogenous cellular GSH content upon 3BP treatment was confirmed to be due to the formation of 3BP-GSH complex i
Thiols↓, Being a thiol blocker, 3BP may attack thiol groups in tissues and serum proteins e.g. albumin and GSH.

3453- 5-ALA,    The heme precursor 5-aminolevulinic acid disrupts the Warburg effect in tumor cells and induces caspase-dependent apoptosis
- in-vitro, Lung, A549
OXPHOS↑, A549 exposed to ALA exhibited enhanced oxidative phosphorylation, which was indicated by an increase in COX protein expression and oxygen consumption.
OCR↑,
Warburg↓, These data demonstrate that ALA inhibits the Warburg effect and induces cancer cell death.
ROS↑, ALA significantly increased O2-generation over 4 h
SOD2↑, ALA stimulates MnSOD, catalase and HO-1 protein expression.
Catalase↑,
HO-1↑,
Casp3↑, ALA induced an increase in the protein expression of activated (cleaved) caspase-3.
Apoptosis↑, these data demonstrate that ALA induced caspase- dependent apoptosis in A549 cells.

2321- ART/DHA,    Dihydroartemisinin mediating PKM2-caspase-8/3-GSDME axis for pyroptosis in esophageal squamous cell carcinoma
- in-vitro, ESCC, Eca109 - in-vitro, ESCC, EC9706
Pyro↑, DHA treatment to ESCC, we found that some dying cells exhibited the characteristic morphology of pyroptosis, such as blowing large bubbles from the cell membrane,
PKM2↓, accompanied by downregulation of pyruvate kinase isoform M2 (PKM2),
Casp8↑, activation of caspase-8/3, and production of GSDME-NT
Casp3↑,
Warburg↓, previous studies, we demonstrated that DHA has anti-esophageal cancer effects by blocking the cell cycle in G0/G1 phase, inducing apoptosis, regulating the NF-κB/HIF-1α/VEGF pathway ... and downregulating the expression of PKM2 to inhibit the Warburg
TumCCA↑,
Apoptosis↑,

2388- Ash,    Withaferin A decreases glycolytic reprogramming in breast cancer
- in-vitro, BC, MDA-MB-231 - 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↓,

2707- BBR,    Berberine exerts its antineoplastic effects by reversing the Warburg effect via downregulation of the Akt/mTOR/GLUT1 signaling pathway
- in-vitro, Liver, HepG2 - in-vitro, BC, MCF-7
GLUT1↓, BBR downregulated the protein expression levels of GLUT1, maintained the cytoplasmic internalization of GLUT1
Akt↓, and suppressed the Akt/mTOR signaling pathway in both HepG2 and MCF7 cell lines
mTOR↓,
ATP↓, BBR-induced decrease in ATP synthesis, glucose uptake, GLUT1 expression and cell proliferation
GlucoseCon↓,
TumCP↓,
Warburg↓, antineoplastic effect of BBR may involve the reversal of the Warburg effect
selectivity↑, The results demonstrated that the colony-forming capacity was slightly inhibited in Hs 578Bst normal breast cells following BBR treatment, but significantly inhibited in both cancer cell lines.
TumCCA↑, BBR effectively induced cell cycle arrest at the G2M phase
Glycolysis↓, Notably, our preliminary experiments identified that BBR strongly decreased the glucose uptake ability of HepG2 and MCF7 cell lines, therefore, it was hypothesized that BBR may interfere with tumor progression by inhibiting glycolysis.

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↓,

5745- Buty,    Microbial Oncotarget: Bacterial-Produced Butyrate, Chemoprevention and Warburg Effect
- Review, Var, NA
selectivity↑, Intriguingly, although butyrate promotes proliferation of normal colonocytes, it has the opposite effect on cancerous cells where it inhibits cell proliferation and also induces apoptosis [5]
HDAC↓, functioned as a histone deacetylase (HDAC) inhibitor to regulate genes that inhibited cell proliferation and promoted apoptosis
TumCP↓,
Apoptosis↑,
Warburg↓, ability to prevent the Warburg effect from occurring in cancerous colonocytes by performing RNAi to deplete an important mediator of the Warburg effect (LDHA)
chemoPv↑, Chemoprevention

5731- Buty,    The Warburg Effect Dictates the Mechanism of Butyrate Mediated Histone Acetylation and Cell Proliferation
- in-vitro, CRC, HCT116 - in-vitro, CRC, HT29
HDAC↓, butyrate accumulated and functioned as an HDAC inhibitor.
Warburg↓, Consequently, butyrate stimulated the proliferation of normal colonocytes and cancerous colonocytes when the Warburg effect was prevented from occurring, whereas it inhibited the proliferation of cancerous colonocytes undergoing the Warburg effect.
TumCP⇅, Butyrate Increases or Decreases Cell Proliferation Depending on the Warburg Effect
HATs↑, Butyrate Induces Histone Acetylation by Stimulating HATs as well as Inhibiting HDACs
BioAv↓, However, the efficacy of butyrate as a chemotherapeutic agent has been limited by its rapid uptake and metabolism by normal cells [resulting in a half-life of 6 minutes and peak blood levels below 0.05 mM (Miller et al., 1987)] before reaching tumors
other↝, A fiber-rich diet might be more successful for chemoprevention because it delivers mM levels of butyrate (via the microbiota) to the correct place (the colon) before the onset of tumorigenesis or at an early stage.
Risk↓, Evidence for this idea comes from recent human studies demonstrating lower levels of butyrate-producing bacteria among the gut microbiota of colorectal cancer patients compared to healthy participants

5737- Buty,    Butyrate Suppresses the Proliferation of Colorectal Cancer Cells via Targeting Pyruvate Kinase M2 and Metabolic Reprogramming
- in-vitro, CRC, HCT116
HDAC↓, thereby functioning as an HDAC inhibitor to inhibit the proliferation of colorectal cancer cells.
TumCP↓, butyrate significantly inhibited the proliferation of HCT116 cells in a dose-dependent manner
PKM2↑, suggested that butyrate binds to and activates pyruvate kinase isoform 2 (PKM2), which is subsequently responsible for reversing the metabolic advantages gained by cancerous colonocytes and ultimately leads to proliferation arrest.
Warburg↓, Butyrate Suppresses the Warburg Effect in Colorectal Cancer Cells

2347- CAP,    Capsaicin ameliorates inflammation in a TRPV1-independent mechanism by inhibiting PKM2-LDHA-mediated Warburg effect in sepsis
- in-vivo, Nor, NA - in-vitro, Nor, RAW264.7
*PKM2↓, capsaicin directly binds to and inhibits PKM2 and LDHA, and further suppresses the Warburg effect in inflammatory macrophages.
*LDHA↓,
*Warburg↓,
*COX2↓, capsaicin targets COX-2 and downregulates its expression in vivo and in vitro.
*Sepsis↓, may function as a novel agent for sepsis and inflammation treatment.
*Inflam↓,
*ECAR↓, CAP notably reduced the ECAR
*OCR↑, LPS decreased the OCR by inhibiting the mitochondrial respiration, and CAP could reverse this decrease

2348- CAP,    Recent advances in analysis of capsaicin and its effects on metabolic pathways by mass spectrometry
- Analysis, Nor, NA
Warburg↓, Capsaicin inhibits the Warburg effect by binding directly to Cys424 residue and LDHA of pyruvate kinase isoenzyme type M2 (PKM2).
*PKM2↓,
*COX2↓, capsaicin targets COX-2 and down-regulates its expression, which results in the further inhibition of inflammation
*Inflam↓,
*Sepsis↓, capsaicin may be used as a new active ingredient to treat sepsis and inflammation
*AMPK↑, capsaicin activates adenylate-activated protein kinase (AMPK) and protein kinase A (PKA), in turn enhancing the activity of the mitochondrial respiratory chain and promoting fatty acid oxidation
*PKA↑,
*mitResp↑,
*FAO↑,
*FASN↓, capsaicin can inhibit the activity of fatty acid synthetase
*PGM1?,
*ATP↑, treatment resulted in increased intracellular ATP levels (the end product of glycolysis)
*ROS↓, Capsaicin can mitigate the negative effects of oxidative stress on human health by scavenging these free radicals and reducing the oxidative stress response.

2393- Cela,    Celastrol mitigates inflammation in sepsis by inhibiting the PKM2-dependent Warburg effect
- in-vivo, Sepsis, NA - in-vitro, Nor, RAW264.7
OS↑, Cel protected mice from lethal endotoxemia and improved their survival with sepsis, and it significantly decreased the levels of pro-inflammatory cytokines in mice and macrophages treated with LPS
PKM2↓, Cel bound to Cys424 of pyruvate kinase M2 (PKM2), inhibiting the enzyme and thereby suppressing aerobic glycolysis (Warburg effect).
Glycolysis↓,
Warburg↓,
Inflam↓, Cel inhibits inflammation and the Warburg effect in sepsis via targeting PKM2 and HMGB1 protein.
HMGB1↓, Cel directly binds PKM2 and HMGB1
ALAT↓, pretreatment with Cel followed by LPS significantly reduced serum levels of ALT, AST and urea (
AST↓,
TNF-α↓, Cel pretreatment also decreased the serum levels of TNF-α, IL-1β and IL-6
IL1β↓,
IL6↓,

2392- Cela,    The role of natural products targeting macrophage polarization in sepsis-induced lung injury
- Review, Sepsis, NA
TNF-α↓, Celastrol suppresses the release of the proinflammatory cytokines TNF-α, IL-1β, and IL-6; inhibits the PKM2-dependent Warburg effec
IL1β↓,
IL6↓,
Warburg↓,
PKM2↓,
NRF2↑, Additionally, celastrol activates the NRF2/HO-1 pathway, inhibits the activation of NF-κB, and reduces the expression of TNF-α, IL-6, IL-1β, and iNOS, further suppressing M1 polarization
HO-1↑,
NF-kB↓,
iNOS↓,
M1↓, further suppressing M1 polarization

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

2307- CUR,    Cell-Type Specific Metabolic Response of Cancer Cells to Curcumin
- in-vitro, Colon, HT29 - in-vitro, Laryn, FaDu
PKM2↓, Siddiqui et al. have recently reported that curcumin downregulates PKM2 expression in cancer cells, consequently decreasing the Warburg effect.
Warburg↓,
mTOR↓, pKM2 downregulation coincided with the inhibition of the mammalian target of rapamycin (mTOR) pathway and consequential downregulation of hypoxia-inducible factor 1-alpha HIF1α
Hif1a↓,
Glycolysis↓, showed that a decrease of PKM2 (mediated by curcumin or by targeted PKM2 silencing) significantly reduces aerobic glycolysis and is also consequential for cell survival.

1875- DCA,    Dichloroacetate inhibits neuroblastoma growth by specifically acting against malignant undifferentiated cells
- in-vitro, neuroblastoma, NA - in-vivo, NA, NA
selectivity↑, acting specifically on the mitochondria of cancer cells without perturbing the physiology of nonmalignant cells.
AntiCan↑, DCA exhibits an unexpected anticancer effect on NB tumor cells
TumVol↓, growth inhibition became statistically significant when mice were treated with 25 mg/kg/dose of DCA (55% of reduction compared with control group)
PDKs↓, effects of DCA are related to PDK inhibition, mitochondrial oxidative phosphorylation activation and specific mitochondrial hyperpolarization reduction,
mt-OXPHOS↑,
MMP↓,
Glycolysis↓, shifting cellular metabolism from glycolysis to glucose oxidation, without any deleterious effect on normal cells.
toxicity↓, Indeed, more than 40 clinical trials of DCA report that the most significant adverse effect of long-term DCA administration is a reversible peripherical neuropathy.
Warburg↓, indeed, DCA is able to reverse the Warburg effect by inhibiting PDK, restoring mitochondrial membrane potential and increasing ROS production.
ROS↑,
eff↑, DCA was celebrated as the magic bullet against cancer, even if it is currently not yet approved for cancer treatment.

1884- DCA,  Sal,    Dichloroacetate and Salinomycin Exert a Synergistic Cytotoxic Effect in Colorectal Cancer Cell Lines
- in-vitro, CRC, DLD1 - in-vitro, CRC, HCT116
eff↑, The effect of combination of dichloracetate and salinomycin on multicellular spheroid size was stronger than the sum of both monotherapies, particularly in HCT116 cells
pH↓, and in contrast, it is not related to dichloroacetate-induced reduction of intracellular pH
PDKs↓, Dichloroacetate (DCA) is a small synthetic molecule that is known as a pyruvate dehydrogenase kinase inhibitor. Its anticancer properties involve reversing the Warburg effect by switching ATP production back to oxidative phosphorylation
Warburg↓,

1873- DCA,    Dual-targeting of aberrant glucose metabolism in glioblastoma
- in-vitro, GBM, U87MG - in-vitro, GBM, U251
PDKs↓, dichloroacetate (DCA), a pyruvate dehydrogenase kinase inhibitor.
eff↑, By combining DCA with PENAO, the two drugs worked synergistically to inhibit cell proliferation (but had no significant effect on non-cancerous cells)
selectivity↑,
MMP↓, induced oxidative stress and depolarized mitochondrial membrane potential, which in turn activated mitochondria-mediated apoptosis
ROS↑,
Apoptosis↑,
Warburg↓, Dichloroacetate (DCA), a pyruvate dehydrogenase kinase (PDK) inhibitor that reverses the Warburg effect
eff↑, DCA has been demonstrated to sensitize cancer cells towards apoptosis and enhance the effects of several anti-cancer agents, including arsenic trioxide [20], cisplatin [22,23] and metformin [24].
Dose∅, IC50 values of DCA were at suprapharmacological millimolar level
toxicity∅, whilst the IC50 values of DCA for non-cancerous cells were not reached (DCA concentration in this study was tested up to 50 mM)

2352- dietFMD,    Glucose restriction reverses the Warburg effect and modulates PKM2 and mTOR expression in breast cancer cell lines
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, MCF-7
Warburg↓, n this study, we investigated the role of glucose restriction (GR) and mTOR inhibition in reversing the Warburg effect in MDA-MB 231 and MCF-7 breast cancer cell lines
mTOR↓, Glucose restriction contribute to the reduction of the Warburg effect through mTOR inhibition and regulation of PKM2 kinases.
PKM2↓, Glucose restriction contribute to the reduction of the Warburg effect through mTOR inhibition and regulation of PKM2 kinases.

1863- dietFMD,  Chemo,    Effect of fasting on cancer: A narrative review of scientific evidence
- Review, Var, NA
eff↑, recommend combining prolonged periodic fasting with a standard conventional therapeutic approach to promote cancer‐free survival, treatment efficacy, and reduce side effects in cancer patients.
ChemoSideEff↓, lowered levels of IGF1 and insulin have the potential to protect healthy cells from side effects
ChemoSen↑,
Insulin↓, causes insulin levels to drop and glucagon levels to rise
HDAC↓, Histone deacetylases are inhibited by ketone bodies, which may slow tumor development.
IGF-1↓, FGF21 rises during intermittent fasting, and it plays a vital role in lowering IGF1 levels by inhibiting phosphorylated STAT5 in the liver
STAT5↓,
BG↓, Fasting suppresses glucose, IGF1, insulin, the MAPK pathway, and heme oxygenase 1
MAPK↓,
HO-1↓,
ATG3↑, while increasing many autophagy‐regulating components (Atgs, LC3, Beclin1, p62, Sirt1, and LAMP2).
Beclin-1↑,
p62↑,
SIRT1↑,
LAMP2↑,
OXPHOS↑, Fasting causes cancer cells to release oxidative phosphorylation (OXPHOS) through aerobic glycolysis
ROS↑, which leads to an increase in reactive oxygen species (ROS), p53 activation, DNA damage, and cell death in response to chemotherapy.
P53↑,
DNAdam↑,
TumCD↑,
ATP↑, and causes extracellular ATP accumulation, which inhibits Treg cells and the M2 phenotype while activating CD8+ cytotoxic T cells.
Treg lymp↓,
M2 MC↓,
CD8+↑,
Glycolysis↓, By lowering glucose intake and boosting fatty acid oxidation, fasting can induce a transition from aerobic glycolysis to mitochondrial oxidative phosphorylation in cancerous cells, resulting in increased ROS
GutMicro↑, Fasting has been shown to have a direct impact on the gut microbial community's constitution, function, and interaction with the host, which is the complex and diverse microbial population that lives in the intestine
GutMicro↑, Fasting also reduces the number of potentially harmful Proteobacteria while boosting the levels of Akkermansia muciniphila.
Warburg↓, Fasting generates an anti‐Warburg effect in colon cancer models, which increases oxygen demand but decreases ATP production, indicating an increase in mitochondrial uncoupling.
Dose↝, Those patients fasted for 36 h before treatment and 24 h thereafter, having a total of 350 calories per day. Within 8 days of chemotherapy, no substantial weight loss was recorded, although there was an improvement in quality of life and weariness.

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

5069- dietSTF,    The Role of Intermittent Fasting in the Activation of Autophagy Processes in the Context of Cancer Diseases
- Review, Var, NA
Risk↓, IF has shown potential for reducing cancer risk and enhancing therapeutic efficacy by sensitizing tumor cells to chemotherapy and radiotherapy.
ChemoSen↑, intermittent fasting (IF) may enhance the effectiveness of chemotherapy and targeted therapies by activating autophagy. IF enhances the effectiveness of chemotherapy, including drugs such as cisplatin, cyclophosphamide, and doxorubicin
RadioS↑, disease stabilization, improved response to radiotherapy patients with glioma
*Dose↝, 16:8—16 h of fasting with an 8 h eating window;
*Dose↝, 5:2—consuming a standard number of calories for 5 days and reducing intake to 25% of daily requirements for 2 days;
*Dose↝, Eat–Stop–Eat—complete fasting for 24–48 h.
*LDL↓, IF during Ramadan (approximately 18 h of fasting for 29–30 days) reduces LDL cholesterol levels and increases HDL cholesterol in women, as well as reducing inflammatory markers such as CRP and TNF-α
*CRP↓,
*TNF-α↓,
TumAuto↓, Intermittent fasting activates autophagy as an adaptive mechanism to nutrient deprivation, which may modulate tumor development and treatment
GLUT1↓, fasting reduces the expression of glucose transporters GLUT1/2, which slow down cancer metabolism and increase the susceptibility of cancer cells to oxidative stress
GLUT2↓,
glucose↓, studies on cell and animal models have shown that intermittent fasting reduces glucose and insulin-like growth factor (IGF-1) levels [103], as well as insulin [104,105], resulting in the inhibition of the mTOR kinase pathway (PI3K/Akt/mTOR), suppress
IGF-1↓,
Insulin↓,
mTOR↓,
mTORC1↓, suppression of mTORC1 [22], and activation of AMPK through increased ADP/ATP ratio in cells, which supports autophagy and induces apoptosis
AMPK↑,
Warburg↓, Moreover, IF counteracts the Warburg effect by promoting oxidative phosphorylation, leading to an increase in the production of reactive oxygen species (ROS) and enhanced oxidative stress in cancer cells [106,108], causing DNA damage and the activati
OXPHOS↑,
ROS↑,
DNAdam↑,
JAK1↓, fasting reduces the production of adenosine by cancer cells, inhibiting the activation of the JAK1/STAT pathway, thereby reducing cancer cell proliferation
STAT↓,
TumCP↓,
QoL↑, reduction in IGF-1 levels, improved quality of life patients with multiple cancer types

649- EGCG,  CUR,  PI,    Targeting Cancer Hallmarks with Epigallocatechin Gallate (EGCG): Mechanistic Basis and Therapeutic Targets
- Review, Var, NA
*BioEnh↑, increase EGCG bioavailability is using other natural products such as curcumin and piperine
EGFR↓,
HER2/EBBR2↓,
IGF-1↓,
MAPK↓,
ERK↓, reduction in ERK1/2 phosphorylation
RAS↓,
Raf↓, Raf-1
NF-kB↓, Numerous investigations have proven that EGCG has an inhibitory effect on NF-κB
p‑pRB↓, EGCG were displayed to reduce the phosphorylation of Rb, and as a result, cells were arrested in G1 phase
TumCCA↑, arrested in G1 phase
Glycolysis↓, EGCG has been found to inhibit key enzymes involved in glycolysis, such as hexokinase and pyruvate kinase, thereby disrupting the Warburg effect and inhibiting tumor cell growth
Warburg↓,
HK2↓,
Pyruv↓,

2313- Flav,    Flavonoids against the Warburg phenotype—concepts of predictive, preventive and personalised medicine to cut the Gordian knot of cancer cell metabolism
- Review, Var, NA
Warburg↓, Flavonoids modulate key pathways involved in the Warburg phenotype including but not limited to PKM2, HK2, GLUT1 and HIF-1.
antiOx↑, Flavonoids represent a diverse group of phytochemicals (Fig. 3) that exhibit antioxidative, antiangiogenic and overall antineoplastic efficacy
angioG↓,
Glycolysis↓, Apigenin (AP) blocked glycolysis through regulation of PKM2 activity and expression in a colon cancer cell line (HCT116)
PKM2↓,
PKM2:PKM1↓, AP is regarded as a potential allosteric inhibitor of PKM2. AP could maintain a low PKM2/PKM1 ratio as a consequence of inhibition of the β-catenin/c-Myc/PTBP1 pathway
β-catenin/ZEB1↓,
cMyc↓,
HK2↓, QUE reduced the level of HK2 and suppressed Akt/mTOR signalling in hepatocellular cancer lines (SMMG-7721, BEL-7402) in vitro.
Akt↓,
mTOR↓,
GLUT1↓, EGCG demonstrated anticancer efficacy against 4T1 via reduction of GLUT1 expression
Hif1a↓, BA suppressed glycolysis via PTEN/Akt/HIF-1α, it is a possible therapeutic sensitiser against gastric cancer

2545- M-Blu,    Reversing the Warburg Effect as a Treatment for Glioblastoma
- in-vitro, GBM, U87MG - NA, AD, NA - in-vitro, GBM, A172 - in-vitro, GBM, T98G
Warburg↓, Here, we documented that methylene blue (MB) reverses the Warburg effect evidenced by the increasing of oxygen consumption and reduction of lactate production in GBM cell lines
OCR↑, increases cellular oxygen consumption, and decreases lactate production in murine hippocampal cells
lactateProd↓,
TumCP↓, MB decreases GBM cell proliferation and halts the cell cycle in S phase.
TumCCA↑,
AMPK↑, Through activation of AMP-activated protein kinase, MB inactivates downstream acetyl-CoA carboxylase and decreases cyclin expression.
ACC↓,
Cyc↓,
neuroP↑, There is mounting evidence that MB enhances brain metabolism and exerts neuroprotective effects in multiple neurodegenerative disease models including Parkinson, Alzheimer, and Huntington disease
Cyt‑c↝, MB has long been known as an electron carrier, which is best represented by MB ability to increase the rate of cytochrome c reduction in isolated mitochondria
Glycolysis↓, MB Decreases Aerobic Glycolysis in U87 Cells
ECAR↓, MB increases OCR and decreases ECAR in U87 cells
TumCG↓, MB Inhibits Tumor Growth in Vitro
other↓, MB dramatically inhibits expression of cyclin A2, B1,and D1 while having less effect on cyclin E1

2542- M-Blu,    In Vitro Methylene Blue and Carboplatin Combination Triggers Ovarian Cancer Cells Death
- in-vitro, Ovarian, OV1369 - in-vitro, Ovarian, OV1946 - in-vitro, Nor, ARPE-19
BioAv↝, our study reveals MB’s distinct cellular uptake, with ARPE-19 absorbing 5 to 7 times more MB than OV1946 and OV1369-R2.
TumCP↓, Treatment with 50 µM MB (MB-50) effectively curtailed the proliferation of both ovarian cancer cell lines.
GlutaM↓, MB-50 exhibited the ability to quell glutaminolysis and the Warburg effect in cancer cell cultures.
Warburg↓,
OCR↑, MB-50 spurred oxygen consumption, disrupted glycolytic pathways, and induced ATP depletion in the chemo-sensitive OV1946 cell line.
Glycolysis↓,
ATP↓,
BioAv↝, The reduced permeability of cancer cell membranes, including mitochondria, suggests limited internalization of MB into their cytoplasm or mitochondria, consistent with their preference for aerobic glycolysis, a hallmark of the Warburg effect.
ROS↑, Consistent with our findings, they reported a decrease in intracellular ATP levels, which, in turn, led to increased generation of reactive oxygen species (ROS)

2540- M-Blu,    Alternative mitochondrial electron transfer for the treatment of neurodegenerative diseases and cancers: Methylene blue connects the dots
- Review, Var, NA - Review, AD, NA
*OCR↑, MB was found to increase oxygen consumption of normal tissues having aerobic glycolysis and of tumors
*Glycolysis↓, Methylene blue increases oxygen consumption, decrease glycolysis, and increases glucose uptake in vitro.
*GlucoseCon↑, Methylene blue enhances glucose uptake and regional cerebral blood flow in rats upon acute treatment.
neuroP↑, methylene blue provides protective effect in neuron and astrocyte against various insults in vitro and in rodent models of Alzheimer’s, Parkinson’s, and Huntington’s disease.
Warburg↓, In glioblastoma cells, methylene blue reverses Warburg effect by enhancing mitochondrial oxidative phosphorylation, arrests glioma cell cycle at s-phase, and inhibits glioma cell proliferation.
mt-OXPHOS↑,
TumCCA↑,
TumCP↓,
ROS⇅, MB has very unique redox property that exists in equilibrium between oxidized state in dark blue (MB) and colorless reduced state (leucomethylene blue), making it both prooxidant and antioxidant under different conditions.
*cognitive↑, Methylene blue feeding improved water-maze and bridge walking performance in 5 X FAD mice. MB enhances memory function in normal rodents potentially through neurometabolic mechanisms
*mTOR↓, MB has been demonstrated to induce autophagy and attenuate tauopathy through inhibition of mTOR signaling both in vitro and in vivo
*mt-antiOx↑, Secondly, the distinct redox property enables MB as a regenerable anti-oxidant in mitochondria that distinct from the traditional free radical scavenges
*memory↑, , MB has been found to improve various experimental memory tasks in rodents
*BBB↑, MB can cross BBB and reach brain at concentrations 10 times higher than that in the circulation
*eff↝, In fibroblast cells, MB has been shown to stimulate 2-deoxyglucose uptake (Louters et al., 2006; Roelofs et al., 2006). Using MRI and PET, we demonstrated that acute treatment of MB significantly enhance glucose uptake
*ECAR↓, MB increased oxygen consumption rate and decreased extracellular acidification rate in both neuronal cells and astrocytes
eff↑, MB has also been used as a tracer for cancer diagnosis and as a photosensitizer for cancer treatment
lactateProd↓, MB increase oxygen consumption rate, decrease lactic acid production and extracellular acidification rate, reduce NADPH, and inhibit proliferation
NADPH↓,
OXPHOS↑, increases oxidative phosphorylation, decreases glycolytic flux and metabolic intermediates, hence, exhausts the building brick for cancer cell proliferation.
AMPK↑, MB is capable of activating AMPK signal pathway
selectivity↑, with low toxicity, and the high affinity to both neuronal and cancer tissues

1782- MEL,    Melatonin in Cancer Treatment: Current Knowledge and Future Opportunities
- Review, Var, NA
AntiCan↑, involvement of melatonin in different anticancer mechanisms
Apoptosis↑, apoptosis induction, cell proliferation inhibition, reduction in tumor growth and metastases
TumCP↓,
TumCG↑,
TumMeta↑,
ChemoSideEff↓, reduction in the side effects associated with chemotherapy and radiotherapy, decreasing drug resistance in cancer therapy,
radioP↑,
ChemoSen↑, augmentation of the therapeutic effects of conventional anticancer therapies
*ROS↓, directly scavenge ROS and reactive nitrogen species (RNS)
*SOD↑, melatonin can regulate the activities of several antioxidant enzymes like superoxide dismutase, glutathione reductase, glutathione peroxidase, and catalase
*GSH↑,
*GPx↑,
*Catalase↑,
Dose∅, demonstrated that 1 mM melatonin concentration is the pharmacological concentration that is able to produce anticancer effects
VEGF↓, downregulatory action on VEGF expression in human breast cancer cells
eff↑, tumor-bearing mice were treated with (10 mg/kg) of melatonin and (5 mg/kg) of cisplatin. The results have shown that melatonin was able to reduce DNA damage
Hif1a↓, MDA-MB-231-downregulation of the HIF-1α gene and protein expression coupled with the production of GLUT1, GLUT3, CA-IX, and CA-XII
GLUT1↑,
GLUT3↑,
CAIX↑,
P21↑, upregulation of p21, p27, and PTEN protein is another way of melatonin to promote cell programmed death in uterine leiomyoma
p27↑,
PTEN↑,
Warburg↓, FIGURE 3
PI3K↓, in colon cancer cells by downregulation of PI3K/AKT and NF-κB/iNOS
Akt↓,
NF-kB↓,
cycD1/CCND1↓,
CDK4↓,
CycB/CCNB1↓,
CDK4↓,
MAPK↑,
IGF-1R↓,
STAT3↓,
MMP9↓,
MMP2↓,
MMP13↓,
E-cadherin↑,
Vim↓,
RANKL↓,
JNK↑,
Bcl-2↓,
P53↑,
Casp3↑,
Casp9↑,
BAX↑,
DNArepair↑,
COX2↓,
IL6↓,
IL8↓,
NO↓,
T-Cell↑,
NK cell↑,
Treg lymp↓,
FOXP3↓,
CD4+↑,
TNF-α↑,
Th1 response↑, FIGURE 3
BioAv↝, varies 1% to 50%?
RadioS↑, melatonin’s radio-sensitizing properties
OS↑, In those individuals taking melatonin, the overall tumor regression rate and the 5-year survival were elevated

994- MET,    Tumor metabolism destruction via metformin-based glycolysis inhibition and glucose oxidase-mediated glucose deprivation for enhanced cancer therapy
- in-vitro, Var, NA
Glycolysis↓,
HK2↓,
ATP↓,
AMPK↑,
P53↑,
Warburg↓,
Apoptosis↑,

2377- MET,    Metformin Inhibits TGF-β1-Induced Epithelial-to-Mesenchymal Transition via PKM2 Relative-mTOR/p70s6k Signaling Pathway in Cervical Carcinoma Cells
- in-vitro, Cerv, HeLa - in-vitro, Cerv, SiHa
EMT↓, metformin partially abolished TGF-β1-induced EMT cell proliferation
P70S6K↓, Metformin decreased the p-p70s6k expression and the blockade of mTOR/p70s6k signaling decreased PKM2 expression.
mTOR↓,
PKM2↓,
Warburg↓, PKM2 regulates in the cancer-specific Warburg effect, which is responsible for the final rate-limiting step of glycolysis.
AMPK↑, direct mechanisms involving activating AMP-activated protein kinase (AMPK), followed by inhibition of the mammalian target of the rapamycin (mTOR) pathway

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

5254- NCL,    The magic bullet: Niclosamide
- Review, Var, NA
Wnt↓, In particular, niclosamide inhibits multiple oncogenic pathways such as Wnt/β-catenin, Ras, Stat3, Notch, E2F-Myc, NF-κB, and mTOR and activates tumor suppressor signaling pathways such as p53, PP2A, and AMPK.
β-catenin/ZEB1↓,
RAS↓,
STAT3↓,
NOTCH↓,
E2Fs↓,
mTOR↓,
eff↑, Moreover, niclosamide potentially improves immunotherapy by modulating pathways such as PD-1/PDL-1.
PD-1↓,
PD-L1↓, primarily through PD-L1 ligand downregulation in cancer cells.
BioAv↝, The original pharmacokinetics study showed that the maximal serum concentration can reach 0.25-6.0ug/ml (0.76-18.34 µM) following administration of a single 2g dose (11).
toxicity↓, a strong safety profile and tolerability in humans.
BioAv↑, A potential solution to the aforementioned challenge is niclosamide ethanolamine (NEN), a salt form of niclosamide that also functions as a mitochondrial uncoupler with a superior safety profile and enhanced bioavailability
ETC↑, NEN activates the ETC to boost NADH oxidation, thereby leading to an increased intracellular NAD+/NADH ratio and driving the TCA cycle forward.
NADH:NAD↓,
TCA↑,
Warburg↓, leading to a reversal of the Warburg effect and the induction of cellular differentiation
Diff↑,
AMPK↑, figure 3
P53↑,
PP2A↑,
HIF-1↓,
KRAS↓,
Myc↓,
RadioS↑, leading to a reversal of the Warburg effect and the induction of cellular differentiation
ChemoSen↑, Niclosamide has shown synergistic anti-tumor effects with a broad spectrum of chemotherapy drugs.
Dose↝, In this trial, either 500mg or 1000mg niclosamide was given three times daily to patients. However, the maximal plasma concentration ranged from 35.7–82 ng/mL (0.1µM-0.25 µM), a range that failed to be consistently above the minimum effective concent
Dose↑, In contrast, the ongoing clinical trial NCT02807805 is administering 1200 mg of reformulated orally bioavailable niclosamide orally (PO) three times daily to patients, resulting in 0.21µM-0.723 plasma niclosamide concentrations exceeding the therape

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

2441- RES,    Anti-Cancer Properties of Resveratrol: A Focus on Its Impact on Mitochondrial Functions
- Review, Var, NA
*toxicity↓, Although resveratrol at high doses up to 5 g has been reported to be non-toxic [34], in some clinical trials, resveratrol at daily doses of 2.5–5 g induced mild-to-moderate gastrointestinal symptoms [
*BioAv↝, After an oral dose of 25 mg in healthy human subjects, the concentrations of native resveratrol (40 nM) and total resveratrol (about 2 µM) in plasma suggested significantly greater bioavailability of resveratrol metabolites than native resveratrol
*Dose↝, The total plasma concentration of resveratrol did not exceed 10 µM following high oral doses of 2–5 g
*hepatoP↑, hepatoprotective effects
*neuroP↑, neuroprotective properties
*AntiAg↑, Resveratrol possesses the ability to impede platelet aggregation
*COX2↓, suppresses promotion by inhibiting cyclooxygenase-2 activity
*antiOx↑, It is widely recognized that resveratrol has antioxidant properties at concentrations ranging from 5 to 10 μM.
*ROS↓, antioxidant properties at concentrations ranging from 5 to 10 μM.
*ROS↑, pro-oxidant properties when present in doses ranging from 10 to 40 μM
PI3K↓, It is known that resveratrol suppresses PI3-kinase, AKT, and NF-κB signaling pathways [75] and may affect tumor growth via other mechanisms as well
Akt↓,
NF-kB↓,
Wnt↓, esveratrol inhibited breast cancer stem-like cells in vitro and in vivo by suppressing Wnt/β-catenin signaling pathway
β-catenin/ZEB1↓,
NRF2↑, Resveratrol activated the Nrf2 signaling pathway, causing separation of the Nrf2–Keap1 complex [84], leading to enhanced transcription of antioxidant enzymes, such as glutathione peroxidase-2 [85] and heme-oxygenase (HO-1)
GPx↑,
HO-1↑,
BioEnh?, Resveratrol was demonstrated to have an impact on drug bioavailability,
PTEN↑, Resveratrol could suppress leukemia cell proliferation and induce apoptosis due to increased expression of PTEN
ChemoSen↑, Resveratrol enhances the sensitivity of cancer cells to chemotherapeutic agents through various mechanisms, such as promoting drug absorption by tumor cells
eff↑, it can also be used in nanomedicines in combination with various compounds or drugs, such as curcumin [101], quercetin [102], paclitaxel [103], docetaxel [104], 5-fluorouracil [105], and small interfering ribonucleic acids (siRNAs)
mt-ROS↑, enhancing the oxidative stress within the mitochondria of these cells, leading to cell damage and death.
Warburg↓, Resveratrol Counteracts Warburg Effect
Glycolysis↓, demonstrated in several studies that resveratrol inhibits glycolysis through the PI3K/Akt/mTOR signaling pathway in human cancer cells
GlucoseCon↓, resveratrol reduced glucose uptake by cancer cells due to targeting carrier Glut1
GLUT1↓,
lactateProd↓, therefore, less lactate was produced
HK2↓, Resveratrol (100 µM for 48–72 h) had a negative impact on hexokinase II (HK2)-mediated glycolysis
EGFR↓, activation of EGFR and downstream kinases Akt and ERK1/2 was observed to diminish upon exposure to resveratrol
cMyc↓, resveratrol suppressed the expression of leptin and c-Myc while increasing the level of vascular endothelial growth factor.
ROS↝, it acts as an antioxidant in regular conditions but as a strong pro-oxidant in cancer cells,
MMPs↓, Main targets of resveratrol in tumor cells. COX-2—cyclooxygenase-2, SIRT-1—sirtuin 1, MMPs—matrix metalloproteinases,
MMP7↓, Resveratrol was shown to exert an inhibitory effect on the expression of β-catenins and also target genes c-Myc, MMP-7, and survivin in multiple myeloma cells, thus reducing the proliferation, migration, and invasion of cancer cells
survivin↓,
TumCP↓,
TumCMig↓,
TumCI↓,

1748- RosA,    The Role of Rosmarinic Acid in Cancer Prevention and Therapy: Mechanisms of Antioxidant and Anticancer Activity
- Review, Var, NA
AntiCan↑, RA exhibits significant potential as a natural agent for cancer prevention and treatment
*BioAv↝, Various factors, including its lipophilic nature, stability in the gastrointestinal tract, and interactions with food, can significantly influence its absorption
*CardioT↓, RA attenuated these effects by reducing ROS levels, indicating its potential role as a cardioprotective agent during chemotherapy.
*Iron↓, Another significant mechanism antioxidant activity of RA is its capacity to chelate transition metal ions, particularly iron (Fe2+) and copper (Cu2+), which can catalyze the formation of highly reactive hydroxyl radicals through the Fenton reaction.
*ROS↓, forming stable complexes with Fe2+ and Cu2+, thus inhibiting their pro-oxidant activity.
*SOD↑, SOD, CAT, and GPx, play crucial roles in neutralizing ROS and maintaining cellular redox homeostasis. RA upregulates the expression and activity of these enzymes
*Catalase↑,
*GPx↑,
*NRF2↑, activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, a primary regulator of the antioxidant response
MARK4↓, Anwar’s study demonstrated that RA inhibited MARK4 activity in MDA-MB-231 breast cancer cells, resulting in dose-dependent apoptosis
MMP9↓, RA effectively inhibited cancer cell invasion and migration by reducing matrix metalloproteinase-9 (MMP-9) activity
TumCCA↑, caused cell cycle arrest
Bcl-2↓, RA downregulates Bcl-2 expression and upregulates Bax, thereby promoting apoptosis
BAX↑,
Apoptosis↑,
E-cadherin↑, promoting E-cadherin expression, while downregulating N-cadherin and vimentin
N-cadherin↓,
Vim↓,
Gli1↓, induced apoptosis by downregulating Gli1, a key component of the Hedgehog signaling pathway,
HDAC2↓, RA induced apoptosis by modulating histone deacetylase 2 (HDAC2) expression
Warburg↓, anti-Warburg effect of RA in colorectal carcinoma
Hif1a↓, RA inhibits hypoxia-inducible factor-1 alpha (HIF-1α) and downregulates miR-155
miR-155↓,
p‑PI3K↑, RA has been shown to upregulate p-PI3K, protecting cells through the PI3K/Akt pathway,
ROS↑, RA, induces significant ROS generation in A549 cells, which triggers both apoptosis and autophagy.
*IronCh↑, RA’s dual nature as both a phenolic acid and a flavonoid-related compound enables it to chelate metal ions and prevent the formation of free radicals,

3006- RosA,    Rosmarinic acid attenuates glioblastoma cells and spheroids’ growth and EMT/stem-like state by PTEN/PI3K/AKT downregulation and ERK-induced apoptosis
- in-vitro, GBM, U87MG - in-vitro, GBM, LN229
TumCG↓, Rosmarinic acid (RA) reduced the glioma growth and motility in 2D- and 3D-cultures
EMT↓, RA suppressed epithelial-mesenchymal transition and stem-cell property in spheroids.
SIRT1↓, RA downregulated SIRT1/FOXO1/NF-κB axis independently of p53 or PTEN function.
FOXO1↓,
NF-kB↓,
angioG↓, RA dose-dependently reduced angiogenesis and intracellular ROS levels, suppressed glioma growth,
ROS↓,
PTEN↓, RA also inhibited the PTEN/PI3K/AKT pathway in U-87MG cells.
PI3K↓,
Akt↓,
*Inflam↓, anti-inflammatory, antimicrobial, cardioprotective, hepatoprotective, neuroprotective, antidiabetic, and especially anticancer effects (
*cardioP↑,
*hepatoP↑,
*neuroP↑,
Warburg↓, suppresses Warburg effect

3003- RosA,    Comprehensive Insights into Biological Roles of Rosmarinic Acid: Implications in Diabetes, Cancer and Neurodegenerative Diseases
- Review, Var, NA - Review, AD, NA - Review, Park, NA
*Inflam↓, anti-inflammatory and antioxidant properties and its roles in various life-threatening conditions, such as cancer, neurodegeneration, diabetes,
*antiOx↑,
*neuroP↑,
*IL6↓, diabetic rat model treated with RA, there is an anti-inflammatory activity reported. This activity is achieved through the inhibition of the expression of various proinflammatory factors, including in IL-6, (IL-1β), tumour
*IL1β↓,
*NF-kB↓, inhibiting NF-κB activity and reducing the production of prostaglandin E2 (PGE2), nitric oxide (NO), and cyclooxygenase-2 (COX-2) in RAW 264.7 cells.
*PGE2↓,
*COX2↓,
*MMP↑, RA inhibits cytotoxicity in tumour patients by maintaining the mitochondrial membrane potential
*memory↑, amyloid β(25–35)-induced AD in rats was treated with RA, which mitigated the impairment of learning and memory disturbance by reducing oxidative stress
*ROS↓,
*Aβ↓, daily consumption of RA diminished the effect of neurotoxicity of Aβ25–35 in mice
*HMGB1↓, SH-SY5Y in vitro and ischaemic diabetic stroke in vivo, and the studies revealed that a 50 mg/kg dose of RA decreased HMGB1 expression
TumCG↓, Rosemary and its extracts have been shown to exhibit potential in inhibiting the growth of cancer cells and the development of tumours in various cancer types, including colon, breast, liver, and stomach cancer
MARK4↓, Another study reported the inhibition of Microtubule affinity regulating kinase 4 (MARK4) by RA
Zeb1↓, Fig 4 BC:
MDM2↓,
BNIP3↑,
ASC↑, Skin Cancer
NLRP3↓,
PI3K↓,
Akt↓,
Casp1↓,
E-cadherin↑, Colon Cancer
STAT3↓,
TLR4↓,
MMP↓,
ICAM-1↓,
AMPK↓,
IL6↑, PC and GC
MMP2↓,
Warburg↓,
Bcl-xL↓, CRC: Apoptosis induction caspases ↑, Bcl-XL ↓, BCL-2 ↓, Induces cell cycle arrest, Inhibition of EMT and invasion, Reduced metastasis
Bcl-2↓,
TumCCA↑,
EMT↓,
TumMeta↓,
mTOR↓, Inhibits mTOR/S6K1 pathway to induce apoptosis in cervical cancer
HSP27↓, Glioma ↓ expression of HSP27 ↑ caspase-3
Casp3↑,
GlucoseCon↓, GC: Inhibited the signs of the Warburg effect, such as high glucose consumption/anaerobic glycolysis, lactate production/cell acidosis, by inhibiting the IL-6/STAT3 pathway
lactateProd↓,
VEGF↓, ↓ angiogenic factors (VEGF) and phosphorylation of p65
p‑p65↓,
GIT1↓, PC: Increased degradation of Gli1
FOXM1↓, inhibiting FOXM1
cycD1/CCND1↓, RA treatment in CRC cells inhibited proliferation-induced cell cycle arrest of the G0/G1 phase by reducing the cyclin D1 and CDK4 levels,
CDK4↓,
MMP9↓, CRC cells, and it led to a decrease in the expressions of matrix metalloproteinase (MMP)-2 and MMP-9.
HDAC2↓, PCa cells through the inhibition of HDAC2

3001- RosA,    Therapeutic Potential of Rosmarinic Acid: A Comprehensive Review
- Review, Var, NA
TumCP↓, including in tumor cell proliferation, apoptosis, metastasis, and inflammation
Apoptosis↑,
TumMeta↓,
Inflam↓,
*antiOx↑, RA is therefore considered to be the strongest antioxidant of all hydroxycinnamic acid derivatives
*AntiAge↑, , it also exerts powerful antimicrobial, anti-inflammatory, antioxidant and even antidepressant, anti-aging effects
*ROS↓, RA and its metabolites can directly neutralize reactive oxygen species (ROS) [10] and thereby reduce the formation of oxidative damage products.
BioAv↑, RA is water-soluble, and according to literature data, the efficacy of secretion of this compound in infusions is about 90%
Dose↝, Accordingly, it is possible to consume approximately 110 mg RA daily, i.e., approximately 1.6 mg/kg for adult men weighing 70 kg.
NRF2↑, liver cancer cell line, HepG2, transfected with plasmid containing ARE-luciferin gene, RA predominantly enhances ARE-luciferin activity and promotes nuclear factor E2-related factor-2 (Nrf2) translocation from cytoplasm to the nucleus
P-gp↑, and also increases MRP2 and P-gp efflux activity along with intercellular ATP level
ATP↑,
MMPs↓, RA concurrently induced necrosis and apoptosis and stimulated MMP dysfunction activated PARP-cleavage and caspase-independent apoptosis.
cl‑PARP↓,
Hif1a↓, inhibits transcription factor hypoxia-inducible factor-1α (HIF-1α) expression
GlucoseCon↓, it also suppressed glucose consumption and lactate production in colorectal cells
lactateProd↓,
Warburg↓, may suppress the Warburg effects through an inflammatory pathway involving activator of transcription-3 (STAT3) and signal transducer of interleukin (IL)-6
TNF-α↓, RA supplementation also reduced tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2) and IL-6 levels, and modulated p65 expression [
COX2↓,
IL6↓,
HDAC2↓, RA induced the cell cycle arrest and apoptosis in prostate cancer cell lines (PCa, PC-3, and DU145) [31]. These effects were mediated through modulation of histone deacetylases expression (HDACs), specifically HDAC2;
GSH↑, RA can also inhibit adhesion, invasion, and migration of Ls 174-T human colon carcinoma cells through enhancing GSH levels and decreasing ROS levels
ROS↓,
ChemoSen↑, RA also enhances chemosensitivity of human resistant gastric carcinoma SGC7901 cells
*BG↓, RA significantly increased insulin index sensitivity and reduced blood glucose, advanced glycation end-products, HbA1c, IL-1β, TNFα, IL-6, p-JNK, P38 mitogen-activated protein kinase (MAPK), and NF-κB levels
*IL1β↓,
*TNF-α↓,
*IL6↓,
*p‑JNK↓,
*p38↓,
*Catalase↑, The reduced activities of CAT, SOD, glutathione S-transferases (GST), and glutathione peroxidase (GPx) and the reduced levels of vitamins C and E, ceruloplasmin, and GSH in plasma of diabetic rats were also significantly recovered by RA application
*SOD↑,
*GSTs↑,
*VitC↑,
*VitE↑,
*GSH↑,
*GutMicro↑, protective effects of RA (30 mg/kg) against hypoglycemia, hyperlipidemia, oxidative stress, and an imbalanced gut microbiota architecture was studied in diabetic rats.
*cardioP↑, Cardioprotective Activity: RA also reduced fasting serum levels of vascular cell adhesion molecule 1 (VCAM-1), inter-cellular adhesion molecule 1 (ICAM-1), plasminogen-activator-inhibitor-1 (PAI-1), and increased GPX and SOD levels
*ROS↓, Finally, in H9c2 cardiac muscle cells, RA inhibited apoptosis by decreasing intracellular ROS generation and recovering mitochondria membrane potential
*MMP↓,
*lipid-P↓, At once, RA suppresses lipid peroxidation (LPO) and ROS generation, whereas in HSC-T6 cells it increases cellular GSH.
*NRF2↑, Additionally, it significantly increases Nrf2 translocation
*hepatoP↑, Hepatoprotective Activity
*neuroP↑, Nephroprotective Activity
*P450↑, RA also reduced CP-produced oxidative stress and amplified cytochrome P450 2E1 (CYP2E1), HO-1, and renal-4-hydroxynonenal expression.
*HO-1↑,
*AntiAge↑, Anti-Aging Activity
*motorD↓, A significantly delays motor neuron dysfunction in paw grip endurance tests,

3036- RosA,    Anti-Warburg effect of rosmarinic acid via miR-155 in colorectal carcinoma cells
- in-vitro, CRC, HCT8 - in-vitro, CRC, HCT116 - in-vitro, CRC, LS174T
GlucoseCon↓, RA suppressed glucose consumption and lactate generation in colorectal carcinoma cells;
lactateProd↓,
Hif1a↓, RA inhibited the expression of transcription factor hypoxia-inducible factor-1α (HIF-1α) that affects the glycolytic pathway.
Inflam↓, RA could not only repress proinflammatory cytokines using enzyme-linked immunosorbent assay but it could also suppress microRNAs related to inflammation by real-time PCR
miR-155↓, MiR-155 induces the Warburg effect and is reversed by RA
STAT3↓, RA could inhibit the expression of transcription factor STAT3, and it suppressed the phosphorylation of STAT3
Glycolysis↓, Meanwhile, RA inhibited the expression of transcription factor HIF-1α that affected the glycolytic pathway
IL6↓, RA could significantly regulate miR-155 and in turn alter the IL-6/STAT3 signaling, resulting in the inhibition of inflammation in the tumor micro environment and the eventual anti-Warburg effect
Warburg↓,

2403- SFN,    Reversal of the Warburg phenomenon in chemoprevention of prostate cancer by sulforaphane
- in-vitro, Pca, LNCaP - in-vitro, Pca, 22Rv1 - in-vitro, Pca, PC3 - in-vivo, NA, NA
ECAR↓, SFN treatment: (i) decreased real-time extracellular acidification rate in LNCaP, but not in PC-3 cell line;
HK2↓, (ii) significantly downregulated expression of hexokinase II (HKII), pyruvate kinase M2 and/or lactate dehydrogenase A (LDHA) in vitro in cells and in vivo . HKII: 32%
PKM2↓, PKM2: 45%
LDHA↓, LDHA: 33%
Glycolysis↓, (iii) significantly suppressed glycolysis in prostate of Hi-Myc mice
Warburg↓, Reversal of the Warburg phenomenon

2417- SK,    Shikonin inhibits the Warburg effect, cell proliferation, invasion and migration by downregulating PFKFB2 expression in lung cancer
- in-vitro, Lung, A549 - in-vitro, Lung, H446
TumCP↓, Shikonin treatment decreased the proliferation, migration, invasion, glucose uptake, lactate levels, ATP levels and PFKFB2 expression levels and increased apoptosis in lung cancer cells in a dose‑dependent manner.
TumCMig↓,
TumCI↓,
GlucoseCon↓,
lactateProd↓,
PFKFB2↓,
Warburg↓, shikonin inhibited the Warburg effect and exerted antitumor activity in lung cancer cells, which was associated with the downregulation of PFKFB2 expression.
GLUT1∅, while the expression levels of the other proteins (PDK1, GLUT1, PGK2, LDHA, PKM2, GLUT3, PDH and p-PDH) were not altered by shikonin treatment.
LDHA∅,
PKM2∅,
GLUT3∅,
PDH∅,

2356- SK,    ESM1 enhances fatty acid synthesis and vascular mimicry in ovarian cancer by utilizing the PKM2-dependent warburg effect within the hypoxic tumor microenvironment
- in-vitro, Ovarian, CaOV3 - in-vitro, Ovarian, OV90 - in-vivo, NA, NA
PKM2↓, Shikonin effectively inhibits the molecular interaction between ESM1 and PKM2, consequently preventing the formation of PKM2 dimers and thereby inhibiting ovarian cancer glycolysis, fatty acid synthesis and vasculogenic mimicry.
Glycolysis↓, Shikonin inhibited glycolysis in OV90 cells
FASN↓,
lactateProd↓, In both CAOV3 and OV90 cells, the levels of lactic acid were significantly reduced in the ESM1 and Shikonin group when compared to the ESM1-overexpressing group
Warburg↓, Shikonin could repress the interaction between PKM2 and ESM1 and the formation of PKM2 dimers to attenuate OC migration and invasion and VM by driving the Warburg effect in vitro.
TumCG↓, Shikonin itself significantly inhibited tumor growth
VM↓, Shikonin significantly attenuates the OC growth and the VM of OC cells

2185- SK,    Shikonin Inhibits Tumor Growth in Mice by Suppressing Pyruvate Kinase M2-mediated Aerobic Glycolysis
- in-vitro, Lung, LLC1 - in-vitro, Melanoma, B16-BL6 - in-vivo, NA, NA
Glycolysis↓, confirming the inhibitory effect of shikonin on tumor aerobic glycolysis
GlucoseCon↓, shikonin dose-dependently inhibited glucose uptake and lactate production in Lewis lung carcinoma (LLC) and B16 melanoma cells
lactateProd↓,
PKM2↓, suppression of cell aerobic glycolysis by shikonin is through decreasing PKM2 activity
selectivity↑, shikonin treatment significantly promoted tumor cell apoptosis compared to untreated control cells.
Warburg↓, agreement with previous findings of shikonin as a Warburg effect inhibitor
TumVol↓, A significant reduction of tumor size (Fig. 7B) and weight (Fig. 7C) was observed when shikonin was injected at concentration of 1 or 10 mg/kg.
TumW↓,

3425- TQ,    Advances in research on the relationship between thymoquinone and pancreatic cancer
Apoptosis↑, TQ can inhibit cell proliferation, promote cancer cell apoptosis, inhibit cell invasion and metastasis, enhance chemotherapeutic sensitivity, inhibit angiogenesis, and exert anti-inflammatory effects.
TumCP↓,
TumCI↓,
TumMeta↓,
ChemoSen↑,
angioG↓,
Inflam↓,
NF-kB↓, These anticancer effects predominantly involve the nuclear factor (NF)-κB, phosphoinositide 3 kinase (PI3K)/Akt, Notch, transforming growth factor (TGF)-β, c-Jun N-terminal kinase (JNK)
PI3K↓,
Akt↓,
TGF-β↓,
Jun↓,
p38↑, and p38 mitogen-activated protein kinase (MAPK) signaling pathways as well as the regulation of the cell cycle, matrix metallopeptidase (MMP)-9 expression, and pyruvate kinase isozyme type M2 (PKM2) activity.
MAPK↑, activation of the JNK and p38 MAPK
MMP9↓,
PKM2↓, decrease in PKM2 activity
ROS↑, ROS-mediated activation
JNK↑, activation of the JNK and p38 MAPK
MUC4↓, downregulation of MUC4;
TGF-β↑, TQ led to the activation of the TGF-β pathway and subsequent downregulation of MUC4
Dose↝, Q acts as an antioxidant (free radical scavenger) at low concentrations and as a pro-oxidant at high concentrations.
FAK↓, TQ can inhibit several key molecules such as FAK, Akt, NF-κB, and MMP-9 and that these molecules interact in a cascade to affect the metastasis of pancreatic cancer
NOTCH↓, TQ involved in increasing chemosensitivity consist of blocking the Notch1/PTEN, PI3K/Akt/mTOR, and NF-κB signaling pathways, reducing PKM2 expression, and inhibiting the Warburg effect.
PTEN↑, it also restored the PTEN protein that had been inhibited by GEM
mTOR↓,
Warburg↓, reducing PKM2 expression, and inhibiting the Warburg effect.
XIAP↓,
COX2↓,
Casp9↑,
Ki-67↓,
CD34↓,
VEGF↓,
MCP1↓,
survivin↓,
Cyt‑c↑,
Casp3↑,
H4↑,
HDAC↓,

3431- TQ,    PI3K-AKT Pathway Modulation by Thymoquinone Limits Tumor Growth and Glycolytic Metabolism in Colorectal Cancer
- in-vitro, CRC, HCT116 - in-vitro, CRC, SW48
Glycolysis↓, we provide evidence that thymoquinone inhibits glycolytic metabolism (Warburg effect) in colorectal cancer cell lines.
Warburg↓,
HK2↓, was due, at least in part, to the inhibition of the rate-limiting glycolytic enzyme, Hexokinase 2 (HK2),
ATP↓, such reduction in glucose fermentation capacity also led to a significant reduction in overall ATP production as well as maintaining the redox state (NADPH production) of these cells
NADPH↓, showed a significant reduction in glucose fermentation, ATP and NADPH production rates
PI3K↓, reduction in HK2 levels upon TQ treatment coincided with significant inhibition in PI3K-AKT activation
Akt↓,
TumCP↓, Thymoquinone Inhibits Cell Migration and Invasion via Modulating Glucose Metabolic Reprogramming
E-cadherin↑, TQ was able to induce E-cadherin while inhibiting N-cadherin expression
N-cadherin↓,
Hif1a↓, TQ is reported to induce cell death in renal cell carcinoma [81] and pancreatic cancers [82] via inhibiting HIF1α and pyruvate kinase M2 (PKM2)-mediated glycolysis
PKM2↓,
GlucoseCon↓, TQ treatment inhibited the glucose uptake and subsequent lactate production in HCT116 and SW480 cells
lactateProd↓,
EMT↓, TQ inhibits cell proliferation, clonogenicity and epithelial-mesenchymal transition (EMT) in CRC cells (HCT116 and SW480)

4846- Uro,    Urolithin A exerts anti-tumor effects on gastric cancer via activating autophagy-Hippo axis and modulating the gut microbiota
- in-vivo, GC, NA
TumCG↓, UroA suppressed tumor progression
Hippo↑, Invigorating of autophagy activated the downstream Hippo pathway, thereby inhibiting the Warburg effect and promoting cell apoptosis.
Warburg↓,
Apoptosis↑,
GutMicro↑, UroA modulated the composition of the gut microbiota, as indicated by the increase of probiotics and the decrease of pathogenic bacteria.

3136- VitC,    Vitamin C uncouples the Warburg metabolic switch in KRAS mutant colon cancer
- in-vitro, Colon, SW48 - in-vitro, Colon, LoVo
ERK↓, Vitamin C induces RAS detachment from the cell membrane inhibiting ERK 1/2 and PKM2 phosphorylation.
p‑PKM2↓,
GLUT1↓, As a consequence of this activity, strong downregulation of the glucose transporter (GLUT-1) and pyruvate kinase M2 (PKM2)
Warburg↓, causing a major blockage of the Warburg effect and therefore energetic stress.
TumCD↑, Vitamin C selectively kills KRAS mutant colon cancer cells alone or in combination with cetuximab
eff↑, Remarkably, treatment of HT29, SW480 and LoVo cells with cetuximab (0,4 μM) and vitamin C (5mM) abolished cell growth in the three lines tested.
ROS↓, Interestingly, we detected that vitamin C treatment dramatically reduced intracellular ROS levels in SW480 and LoVo cells (Figure 2D),
cMyc↓, strong inhibition of c-Myc oncogene in colonospheres treated at concentrations of vitamin C as low as 100 μM

3138- VitC,    The Hypoxia-inducible Factor Renders Cancer Cells More Sensitive to Vitamin C-induced Toxicity
- in-vitro, RCC, RCC4 - in-vitro, CRC, HCT116 - in-vitro, BC, MDA-MB-435 - in-vitro, Ovarian, SKOV3 - in-vitro, Colon, SW48 - in-vitro, GBM, U251
eff↑, Here, we show that a Warburg effect triggered by activation of the hypoxia-inducible factor (HIF) pathway greatly enhances Vc-induced toxicity in multiple cancer cell lines
Warburg↓,
BioAv↑, HIF increases the intracellular uptake of oxidized Vc through its transcriptional target glucose transporter 1 (GLUT1),
ROS↑, resulting high levels of intracellular Vc induce oxidative stress and massive DNA damage, which then causes metabolic exhaustion by depleting cellular ATP reserves.
DNAdam↑,
ATP↓,
eff↑, Activation of HIF increases the susceptibility to Vc-induced cell toxicity
necrosis↑, High intracellular levels of Vc increase ROS and trigger necrosis in VHL-defective renal cancer cells.
PARP↑, Activation of the PARP Pathway by Vc Depletes Intracellular ATP Reserves in VHL-defective Renal Cancer Cells

3140- VitC,    Vitamin-C-dependent downregulation of the citrate metabolism pathway potentiates pancreatic ductal adenocarcinoma growth arrest
- in-vitro, PC, MIA PaCa-2 - in-vitro, Nor, HEK293
citrate↓, pharmacological doses of vitamin C are capable of exerting an inhibitory action on the activity of CS, reducing glucose-derived citrate levels
FASN↓, Moreover, ascorbate targets citrate metabolism towards the de novo lipogenesis pathway, impairing fatty acid synthase (FASN) and ATP citrate lyase (ACLY) expression.
ACLY↓,
LDH↓, correlated with a remarkable decrease in extracellular pH through inhibition of lactate dehydrogenase (LDH) and overall reduced glycolytic metabolism.
Glycolysis↓,
Warburg↓, Dismissed citrate metabolism correlated with reduced Warburg effectors such as the pyruvate dehydrogenase kinase 1 (PDK1) and the glucose transporter 1 (GLUT1),
PDK1↓,
GLUT1↓,
LDHA↓, Reduced LDHA expression was also observed after vitamin C exposure, leading to a vast extracellular acidification rate (ECAR) reduction.
ECAR↓,
PDH↑, enhancing PDH activity
eff↑, Surprisingly, an impressive 85% of tumor growth inhibition is described in the combinatory treatment of vitamin C and gemcitabine in our preclinical PDAC PDX model

3137- VitC,    Vitamin C inhibits the growth of colorectal cancer cell HCT116 and reverses the glucose-induced oncogenic effect by downregulating the Warburg effect
- in-vitro, CRC, HCT116
Warburg↓, Notably, as a potential Warburg effect inhibitor, VC suppressed cancer growth in a concentration-dependent manner
TumCG↓,


Showing Research Papers: 1 to 50 of 54
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* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 54

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   Catalase↑, 1,   GPx↑, 1,   GSH↓, 1,   GSH↑, 1,   HO-1↓, 1,   HO-1↑, 3,   NRF2↑, 3,   OXPHOS↓, 1,   OXPHOS↑, 4,   mt-OXPHOS↑, 2,   ROS↓, 3,   ROS↑, 12,   ROS⇅, 1,   ROS↝, 1,   mt-ROS↑, 1,   RPM↑, 1,   SIRT3↑, 1,   SOD2↑, 1,   Thiols↓, 1,   TKT↝, 1,  

Mitochondria & Bioenergetics ⓘ

ADP:ATP↓, 1,   ATP↓, 8,   ATP↑, 2,   ETC↑, 1,   Insulin↓, 2,   MMP↓, 3,   OCR↑, 4,   Raf↓, 1,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

ACC↓, 1,   ACLY↓, 1,   ALAT↓, 1,   AminoA↓, 1,   AMPK↓, 1,   AMPK↑, 7,   ATP:AMP↓, 1,   CAIX↑, 1,   citrate↓, 1,   cMyc↓, 5,   ECAR↓, 3,   FASN↓, 2,   G6PD↓, 1,   glucose↓, 1,   GlucoseCon↓, 11,   GLUT2↓, 2,   GlutaM↓, 1,   Glycolysis↓, 22,   HK2↓, 10,   lactateProd↓, 12,   LDH↓, 3,   LDHA↓, 2,   LDHA∅, 1,   NADH:NAD↓, 1,   NADPH↓, 2,   PDH↑, 2,   PDH∅, 1,   PDK1↓, 2,   PDKs↓, 3,   PFK↓, 1,   PFK1↓, 3,   PFK2↓, 1,   PFKFB2↓, 1,   PKM2↓, 15,   PKM2↑, 1,   PKM2∅, 1,   p‑PKM2↓, 1,   PKM2:PKM1↓, 1,   Pyruv↓, 2,   R5P↝, 1,   SIRT1↓, 1,   SIRT1↑, 2,   TCA↑, 1,   Warburg↓, 49,  

Cell Death ⓘ

Akt↓, 8,   Apoptosis↑, 12,   BAX↑, 2,   Bcl-2↓, 3,   Bcl-xL↓, 1,   Casp1↓, 1,   Casp3↑, 5,   Casp8↑, 1,   Casp9↑, 2,   Cyt‑c↑, 1,   Cyt‑c↝, 1,   Hippo↑, 1,   iNOS↓, 1,   JNK↑, 2,   MAPK↓, 2,   MAPK↑, 2,   MDM2↓, 1,   Myc↓, 1,   necrosis↑, 1,   p27↑, 1,   p38↑, 1,   Pyro↑, 1,   survivin↓, 2,   TumCD↑, 2,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 1,  

Transcription & Epigenetics ⓘ

H4↑, 1,   HATs↑, 1,   miR-145↑, 1,   other↓, 1,   other↝, 1,   p‑pRB↓, 1,   TET3↑, 1,  

Protein Folding & ER Stress ⓘ

ER Stress↑, 1,   GRP78/BiP↑, 1,   HSP27↓, 1,  

Autophagy & Lysosomes ⓘ

ATG3↑, 1,   Beclin-1↑, 1,   BNIP3↑, 1,   LAMP2↑, 1,   p62↑, 1,   TumAuto↓, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 3,   DNArepair↑, 1,   P53↑, 4,   PARP↑, 1,   cl‑PARP↓, 1,  

Cell Cycle & Senescence ⓘ

CDK4↓, 3,   Cyc↓, 1,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 2,   E2Fs↓, 1,   P21↑, 1,   TumCCA↑, 7,  

Proliferation, Differentiation & Cell State ⓘ

CD34↓, 1,   CSCs↓, 1,   Diff↑, 1,   EMT↓, 4,   ERK↓, 2,   FOXM1↓, 1,   FOXO1↓, 1,   Gli1↓, 1,   HDAC↓, 5,   HDAC2↓, 3,   IGF-1↓, 3,   IGF-1R↓, 1,   Jun↓, 1,   mTOR↓, 10,   mTORC1↓, 1,   NOTCH↓, 2,   P70S6K↓, 1,   PI3K↓, 8,   p‑PI3K↑, 1,   PTEN↓, 1,   PTEN↑, 4,   RAS↓, 2,   STAT↓, 1,   STAT3↓, 4,   STAT5↓, 1,   TumCG↓, 8,   TumCG↑, 1,   Wnt↓, 2,  

Migration ⓘ

E-cadherin↑, 4,   FAK↓, 1,   GIT1↓, 1,   Ki-67↓, 1,   KRAS↓, 1,   MARK4↓, 2,   miR-155↓, 2,   MMP13↓, 1,   MMP2↓, 2,   MMP7↓, 1,   MMP9↓, 4,   MMPs↓, 2,   MUC4↓, 1,   N-cadherin↓, 2,   PKA↓, 1,   talin↓, 1,   TGF-β↓, 1,   TGF-β↑, 1,   Treg lymp↓, 2,   TumCI↓, 4,   TumCMig↓, 2,   TumCP↓, 15,   TumCP⇅, 1,   TumMeta↓, 3,   TumMeta↑, 1,   Vim↓, 2,   Zeb1↓, 1,   β-catenin/ZEB1↓, 3,  

Angiogenesis & Vasculature ⓘ

angioG↓, 4,   EGFR↓, 2,   HIF-1↓, 1,   Hif1a↓, 9,   NO↓, 1,   VEGF↓, 3,   VM↓, 1,  

Barriers & Transport ⓘ

GLUT1↓, 10,   GLUT1↑, 1,   GLUT1∅, 1,   GLUT3↑, 1,   GLUT3∅, 1,   P-gp↑, 1,  

Immune & Inflammatory Signaling ⓘ

ASC↑, 1,   CD4+↑, 1,   COX2↓, 3,   FOXP3↓, 1,   HMGB1↓, 1,   ICAM-1↓, 1,   IL1β↓, 2,   IL6↓, 5,   IL6↑, 1,   IL8↓, 1,   Inflam↓, 4,   JAK1↓, 1,   M1↓, 1,   M2 MC↓, 1,   MCP1↓, 1,   NF-kB↓, 6,   p‑NF-kB↓, 1,   NK cell↑, 1,   p‑p65↓, 1,   PD-1↓, 1,   PD-L1↓, 1,   T-Cell↑, 1,   Th1 response↑, 1,   TLR4↓, 1,   TNF-α↓, 3,   TNF-α↑, 1,  

Cellular Microenvironment ⓘ

pH↓, 1,  

Protein Aggregation ⓘ

NLRP3↓, 1,   PP2A↑, 1,  

Hormonal & Nuclear Receptors ⓘ

RANKL↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 3,   BioAv↝, 4,   BioEnh?, 1,   ChemoSen↑, 8,   Dose↑, 1,   Dose↝, 4,   Dose∅, 3,   eff↑, 14,   RadioS↑, 3,   selectivity↑, 7,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   AST↓, 1,   BG↓, 2,   EGFR↓, 2,   FOXM1↓, 1,   GutMicro↑, 3,   HER2/EBBR2↓, 1,   IL6↓, 5,   IL6↑, 1,   Ki-67↓, 1,   KRAS↓, 1,   LDH↓, 3,   Myc↓, 1,   PD-L1↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 4,   chemoPv↑, 1,   ChemoSideEff↓, 2,   neuroP↑, 2,   OS↑, 2,   QoL↑, 1,   radioP↑, 1,   Risk↓, 2,   toxicity↓, 2,   toxicity∅, 1,   TumVol↓, 2,   TumW↓, 1,  

Infection & Microbiome ⓘ

CD8+↑, 1,  
Total Targets: 264

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 3,   mt-antiOx↑, 1,   Catalase↑, 3,   GPx↑, 2,   GSH↑, 2,   GSTs↑, 1,   HO-1↑, 1,   Iron↓, 1,   lipid-P↓, 1,   NRF2↑, 2,   ROS↓, 8,   ROS↑, 1,   mt-ROS↑, 1,   SOD↑, 3,   VitC↑, 1,   VitE↑, 1,  

Metal & Cofactor Biology ⓘ

IronCh↑, 1,  

Mitochondria & Bioenergetics ⓘ

ADP:ATP↓, 1,   ATP↑, 1,   mitResp↑, 1,   MMP↓, 1,   MMP↑, 1,   OCR↑, 2,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   ECAR↓, 3,   FAO↑, 1,   FASN↓, 1,   GlucoseCon↑, 1,   Glycolysis↓, 1,   lactateProd↓, 1,   LDHA↓, 1,   LDL↓, 1,   PGM1?, 1,   PKM2↓, 2,   PPP↓, 1,   Warburg↓, 1,  

Cell Death ⓘ

p‑JNK↓, 1,   p38↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

mTOR↓, 1,  

Migration ⓘ

AntiAg↑, 1,   PKA↑, 1,  

Angiogenesis & Vasculature ⓘ

Hif1a∅, 1,  

Barriers & Transport ⓘ

BBB↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 4,   CRP↓, 1,   HMGB1↓, 1,   IL1β↓, 2,   IL6↓, 2,   Inflam↓, 4,   NF-kB↓, 1,   PGE2↓, 1,   TNF-α↓, 2,  

Protein Aggregation ⓘ

Aβ↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↝, 2,   BioEnh↑, 1,   Dose↝, 4,   eff↝, 1,   P450↑, 1,  

Clinical Biomarkers ⓘ

BG↓, 1,   CRP↓, 1,   GutMicro↑, 1,   IL6↓, 2,  

Functional Outcomes ⓘ

AntiAge↑, 2,   cardioP↑, 2,   CardioT↓, 1,   cognitive↑, 1,   hepatoP↑, 3,   memory↑, 2,   motorD↓, 1,   neuroP↑, 4,   toxicity↓, 1,  

Infection & Microbiome ⓘ

Sepsis↓, 2,  
Total Targets: 72

Scientific Paper Hit Count for: Warburg, Warburg Effect
6 Vitamin C (Ascorbic Acid)
5 Rosmarinic acid
3 Butyrate
3 Dichloroacetate
3 diet FMD Fasting Mimicking Diet
3 Methylene blue
3 Shikonin
2 Berberine
2 Capsaicin
2 Celastrol
2 Curcumin
2 Chemotherapy
2 Metformin
2 Resveratrol
2 Thymoquinone
2 Vitamin D3
1 3-bromopyruvate
1 5-Aminolevulinic acid
1 Artemisinin
1 Ashwagandha(Withaferin A)
1 Citric Acid
1 salinomycin
1 diet Short Term Fasting
1 EGCG (Epigallocatechin Gallate)
1 Piperine
1 flavonoids
1 Melatonin
1 Magnetic Fields
1 Niclosamide (Niclocide)
1 Sulforaphane (mainly Broccoli)
1 Urolithin
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#:947  State#:%  Dir#:1
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