Metformin Cancer Research Results

MET, Metformin: Click to Expand ⟱
Features: oral antidiabetic agent,
Metformin is a pleiotropic drug: attributed to its action on AMPK
Metformin is a biguanide drug used primarily for type 2 diabetes. Mechanistically, it is best described as a bioenergetic modulator: partial inhibition of mitochondrial respiration can raise AMP/ADP, engage AMPK, and suppress mTORC1 signaling; systemically it reduces hepatic gluconeogenesis and can lower insulin/IGF-1 growth signaling. In oncology, observational studies suggested improved outcomes in some settings, but randomized trial data are mixed (e.g., large adjuvant breast cancer data did not show broad benefit overall). Long-term use can be associated with vitamin B12 deficiency, and prescribing requires attention to renal function due to rare lactic acidosis risk in predisposed states.
Metformin directly(partially) inhibits Complex I of the electron transport chain (ETC) in mitochondria. This inhibition decreases mitochondrial ATP production and forces cells to rely more on glycolysis for energy.
Cancer cells, especially those with high energy demands, may be particularly sensitive to a drop in ATP levels. The inhibition of Complex I also increases the AMP/ATP ratio, setting the stage for the activation of downstream energy stress pathways.
AMPK activation results in the inhibition of the mammalian target of rapamycin (mTOR) pathway, a central regulator of protein synthesis and cellular growth. mTOR inhibition reduces cell proliferation and limits tissue growth, which can slow tumor progression.

Metformin reduces circulating insulin levels, which in turn can decrease the activation of the insulin and insulin-like growth factor-1 (IGF-1) receptor pathways.

ETC Inhibitors: Drugs that directly inhibit specific ETC complexes (e.g., Complex I inhibitors like metformin or phenformin) can increase electron leakage and ROS production.(dose- and context-dependent, and not consistent)

-known as mild OXPHOS inhibitor(Complex I modulator)

Metformin — a synthetic hydrophilic biguanide and oral glucose-lowering drug used primarily for type 2 diabetes mellitus. It is formally classified as a biguanide antihyperglycemic agent and is commonly abbreviated MET. Its pharmacological lineage derives from the guanidine compound galegine found in Galega officinalis, although modern metformin is synthetic. In oncology it is best regarded as a metabolic/bioenergetic modulator rather than a conventional cytotoxic chemotherapy drug. Its proposed anticancer activity combines direct cellular energy stress with systemic reductions in glucose/insulin-driven growth signaling, but clinical translation has been substantially weaker than the extensive preclinical literature initially suggested.

Primary mechanisms (ranked):

  1. Mitochondrial respiratory Complex I/OXPHOS inhibition or modulation, producing cellular energy stress and reduced ATP availability; the magnitude at clinically achievable concentrations remains debated.
  2. AMPK activation through altered cellular energy state and additional lysosomal/signaling mechanisms, with downstream suppression of anabolic growth programs.
  3. mTORC1 suppression through AMPK-TSC2/Raptor-dependent and reported AMPK-independent mechanisms, reducing protein synthesis and proliferative signaling.
  4. Systemic suppression of hepatic gluconeogenesis and hyperinsulinemia, potentially reducing insulin/IGF-1-mediated tumor growth signaling.
  5. Metabolic reprogramming involving glycolysis, PKM2, HIF-1α and mitochondrial substrate utilization in susceptible tumor contexts.
  6. Cell-cycle inhibition and apoptosis under metabolic stress, particularly in nutrient-poor or metabolically vulnerable tumor models.
  7. Inhibition of EMT, invasion and migration through HIF-1α, mTOR, STAT3, TGF-β and related signaling networks.
  8. ROS/redox modulation as a secondary, dose- and context-dependent mechanism; ROS may increase in metabolically stressed cancer cells while antioxidant effects can occur in normal tissues.
  9. Chemo- and radiosensitization in selected experimental systems; this remains context-dependent and has not translated into consistent survival benefit in randomized oncology trials.

Bioavailability / PK relevance: Oral bioavailability is approximately 50–60%. Metformin is highly hydrophilic, requires membrane transporters such as OCT and MATE family proteins for tissue disposition, undergoes essentially no metabolism, and is eliminated unchanged primarily by the kidneys. The multiple-dose elimination half-life in subjects with preserved renal function is approximately 5 hours. A 1 g oral dose commonly produces peak plasma concentrations in the tens-of-micromolar range rather than the millimolar range frequently used experimentally. Renal impairment can markedly increase exposure.

In-vitro vs systemic exposure relevance: This is a major translational limitation. Many direct anticancer experiments use approximately 0.5–10 mM metformin, and some use still higher concentrations, whereas usual therapeutic plasma exposure is generally in the low tens-of-micromolar range. Therefore, strong direct Complex I inhibition, ATP depletion, ROS generation, apoptosis and glycolytic suppression observed at millimolar concentrations should not automatically be interpreted as achievable in human tumors at standard oral dosing. Tumor accumulation occurs and is heterogeneous, but measured human tumor concentrations remain substantially below many standard cell-culture exposures.
-a 1-g dose has been reported to peak around 20–30 µM, whereas much of the mechanistic cancer literature uses 1–10 mM.

Clinical evidence status: RCT / investigational adjunct. Metformin is an established prescription treatment for type 2 diabetes but is not an approved anticancer therapy. Numerous observational studies report associations with lower cancer incidence or improved outcomes, particularly in diabetic populations, but randomized evidence has not demonstrated a general anticancer survival benefit. The large MA.32 breast-cancer trial was negative for its primary outcome in the overall population, and meta-analyses of randomized oncology trials have generally found no significant improvement in progression-free or overall survival. Current evidence therefore supports mechanistic and investigational adjunct relevance rather than established cancer therapy.

Safety / clinical constraints: Gastrointestinal adverse effects are common. Long-term therapy can contribute to vitamin B12 deficiency. Metformin-associated lactic acidosis is rare but potentially severe, with risk increasing when drug accumulation or tissue hypoxia occurs, particularly with significant renal dysfunction. Renal function is therefore a major determinant of safe dosing and systemic exposure.

Metformin Cancer Mechanisms

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 Mitochondrial Complex I and OXPHOS Complex I ↓; OCR ↓; ATP ↓ (dose-dependent) Mitochondrial respiration ↓ (mild) P, R Bioenergetic stress Central mechanistic hypothesis, but pronounced direct Complex I inhibition often requires concentrations above ordinary human plasma exposure.
2 AMPK energy-sensing pathway AMPK ↑; p-AMPK ↑ AMPK ↑ R Energy-stress adaptation Can follow altered AMP/ADP/ATP balance; clinically relevant concentrations may also engage AMPK through mechanisms not requiring severe ATP depletion.
3 mTORC1 anabolic signaling mTORC1 ↓; p70S6K ↓; protein synthesis ↓ Anabolic signaling ↓ (context-dependent) R, G Growth suppression AMPK-TSC2 and AMPK-Raptor mechanisms are well characterized; AMPK-independent mTOR regulation has also been reported.
4 Insulin and IGF growth signaling Mitogenic insulin/IGF signaling ↓ indirectly Insulin resistance ↓; circulating insulin ↓ G Systemic growth-factor reduction Potentially important clinically because it does not require millimolar intratumoral metformin; likely most relevant in insulin-resistant or hyperinsulinemic patients.
5 Glycolysis and PKM2 metabolic programming PKM2 ↓; glycolysis ↓ or compensatory ↑ (context-dependent); lactate production ↓ in several models Glucose production ↓; metabolic homeostasis ↑ R, G Metabolic reprogramming Direction depends strongly on tumor type, nutrient availability and degree of respiratory inhibition; compensatory glycolysis can increase when OXPHOS is inhibited.
6 HIF-1α hypoxic metabolic signaling HIF-1α ↓; hypoxic glycolytic program ↓ ↔ or ↓ (context-dependent) G Hypoxia adaptation suppression Reported across several tumor models and can converge with PKM2, STAT3 and glycolytic regulation.
7 Cell cycle and apoptosis Proliferation ↓; Cyclin D1 ↓; apoptosis ↑ Usually limited cytotoxicity at therapeutic exposure G Cytostasis and conditional cell death Often secondary to prolonged energy stress and mTOR suppression. Strong apoptosis is particularly common at millimolar concentrations or under nutrient limitation.
8 EMT invasion and migration EMT ↓; migration ↓; invasion ↓; E-cadherin ↑ ↔ G Reduced metastatic phenotype Reported through mTOR, HIF-1α, PKM2, STAT3, TGF-β and related networks; primarily preclinical evidence.
9 Mitochondrial ROS and redox stress ROS ↑ (secondary, dose-dependent); GSH ↓ and NRF2 ↓ in selected models ROS ↓; NRF2 ↑ reported in protective contexts P, R Context-dependent redox modulation ROS increase is not a universal primary metformin mechanism. Strong pro-oxidant effects frequently occur under high concentration, combination treatment or metabolic stress.
10 Autophagy and stress adaptation Autophagy ↑ or ↓ (model-dependent) Cellular stress adaptation ↑ (context-dependent) G Adaptive metabolic response AMPK and mTOR regulation can promote autophagy, but downstream consequences can be either tumor-suppressive or tumor-protective.
11 Chemosensitization Drug sensitivity ↑ (model-dependent) Variable G Adjunct treatment effect Synergy has been reported with several cytotoxic and targeted agents, including effects at micromolar metformin concentrations in some models; randomized clinical evidence has not demonstrated a general survival advantage.
12 Radiosensitization Radiation sensitivity ↑ (model-dependent) Variable G Adjunct radiation response Preclinical evidence exists, potentially involving metabolic stress, AMPK and tumor oxygen/redox effects; not an established clinical indication.
13 Clinical Translation Constraint Direct effects often require supra-pharmacologic exposure Renal clearance determines accumulation and toxicity risk G Exposure and efficacy limitation Typical human plasma concentrations are micromolar whereas many anticancer experiments use millimolar metformin. Tumor uptake is heterogeneous, and randomized trials have not demonstrated broad anticancer efficacy.

TSF: P: 0–30 min    R: 30 min–3 hr    G: >3 hr
Scientific Papers found: Click to Expand⟱
291- ALA,  HCA,  MET,  DFC,    Metabolic therapies inhibit tumor growth in vivo and in silico
- in-vivo, Melanoma, B16-F10 - in-vivo, Lung, LL/2 (LLC1) - in-vivo, Bladder, MBT-2
TumCG↓,
1563- Api,  MET,    Metformin-induced ROS upregulation as amplified by apigenin causes profound anticancer activity while sparing normal cells
- in-vitro, Nor, HDFa - in-vitro, PC, AsPC-1 - in-vitro, PC, MIA PaCa-2 - in-vitro, Pca, DU145 - in-vitro, Pca, LNCaP - in-vivo, NA, NA
selectivity↑, selectivity↑, selectivity↓, ROS↑, Synergy↑, tumCV↓, MMP↓, Dose∅, eff↓, DNAdam↑, Apoptosis↑, TumAuto↑, Necroptosis↑, p‑P53↑, BIM↑, BAX↑, p‑PARP↑, Casp3↑, Casp8↑, Casp9↑, Cyt‑c↑, Bcl-2↓, AIF↑, p62↑, LC3B↑, MLKL↑, p‑MLKL↓, RIP3↑, p‑RIP3↑, TumCG↑, TumW↓,
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↓, NADPH↓, ROS↑, TumCD↑, AMPK↑, Hif1a↓, GLUT1↓, GLUT3↓, HK2↓, PFK↓, PKM2↓, LDH↓, cMyc↓, BAX↓, cycD1/CCND1↓, PDH↓, ROS↑, Apoptosis↑, eff↑, ACLY↓, FASN↓, Bcl-2↓, Glycolysis↓,
6132- CHr,  MET,    Synergistic Growth Inhibitory Effects of Chrysin and Metformin Combination on Breast Cancer Cells through hTERT and Cyclin D1 Suppression
- in-vitro, BC, T47D
Synergy↑, cycD1/CCND1↓, hTERT/TERT↓, TumCP↓, Apoptosis↑, TumCI↓, TumMeta↓, angioG↓, selectivity↑,
1868- DCA,  MET,    Long-term stabilization of stage 4 colon cancer using sodium dichloroacetate therapy
- Case Report, CRC, NA
eff↑, toxicity∅, MMP↓, Apoptosis↑, selectivity↑, pH↝, Dose↝, Dose↝, ChemoSen↑,
1866- DCA,  MET,  BTZ,    Targeting metabolic pathways alleviates bortezomib-induced neuropathic pain without compromising anticancer efficacy in a sex-specific manner
- in-vivo, Var, NA
Synergy↑, TumCG↓, Hif1a↓, PDH↑, lactateProd↓, TumVol↓, TumW↓, Glycolysis↑, neuroP↑,
1864- DCA,  MET,    Dichloroacetate Enhances Apoptotic Cell Death via Oxidative Damage and Attenuates Lactate Production in Metformin-Treated Breast Cancer Cells
- in-vitro, BC, MCF7 - in-vitro, BC, T47D - in-vitro, Nor, MCF10
PDKs↓, Synergy↑, ROS↑, PDK1 / PDPK1↓, lactateProd↓, p‑PDH↑, Dose∅, OCR↑, DNA-PK↑, γH2AX↑, cl‑PARP↑, selectivity↑, *toxicity∅,
6706- DFC,  MET,    Frontiers | Combined Metabolic Targeting With Metformin and the NSAIDs Diflunisal and Diclofenac Induces Apoptosis in Acute Myeloid Leukemia Cells
- in-vitro, AML, U937
lactateProd↓, TumCP↓, Synergy↑, Glycolysis↓,
6696- DFC,  MET,    Combined Modulation of Tumor Metabolism by Metformin and Diclofenac in Glioma
- in-vitro, GBM, GBM
compI↓, Glycolysis↓, OCR↓, Glycolysis↑, lactateProd↓, eff↑, TumCP↓, TumCMig↓, TumCD∅,
6996- Form,  MET,    Formononetin and metformin act synergistically to inhibit growth of MCF-7 breast cancer cells in vitro
- in-vitro, BC, MCF7
TumCP↓, Apoptosis↑, Bcl-2↓, p‑ERK↓, Synergy↑,
7051- Gallo,  MET,    Galloflavin Plus Metformin Treatment Impairs Pancreatic Cancer Cells
- in-vitro, PC, MIA PaCa-2
LDH↓, TumCP↓, TumCD↑, Synergy↑,
1154- HNK,  MET,    Honokiol inhibits the growth of hormone-resistant breast cancer cells: its promising effect in combination with metformin
- in-vitro, BC, MCF7 - in-vitro, BC, SkBr3 - in-vitro, BC, MDA-MB-231
cl‑PARP↑, Bcl-2↓, ERα/ESR1↓,
7466- HNK,  PDT,  MET,    Enhanced integrated therapy for breast cancer employing Honokiol-loaded mesoporous polydopamine nanoparticles in conjunction with photothermal effects and low-dose metformin
- in-vitro, BC, NA
TumCD↓, Dose↝, cl‑Casp3↑, cl‑PARP↑, Apoptosis↑, TumCP↓,
5800- MET,    Metformin as anticancer agent and adjuvant in cancer combination therapy: Current progress and future prospect
- Review, Var, NA
ChemoSen↑, RadioS↑, Imm↑, *AntiDiabetic↑, *AMPK↑, TumCP↓, hepatoP↑, ATP↓, AMP↑, glucoNG↓, ROS↑, compI↓, DNAdam↑, CSCs↓, NP/CIPN↓, chemoP↑, toxicity↓, Trx↓, Synergy↑, cycD1/CCND1↓, CDK4↓, CDK6↓, cycE/CCNE↓, CDK2↓,
5803- MET,  carbop,    Metformin, at Concentrations Corresponding to the Treatment of Diabetes, Potentiates the Cytotoxic Effects of Carboplatin in Cultures of Ovarian Cancer Cells
- in-vitro, Ovarian, A2780S - in-vitro, Ovarian, SKOV3
eff↑, ChemoSen↑, TumCCA↑,
5804- MET,  NIV,    Durable Response to Nivolumab Combined With Metformin in Advanced Pancreatic Cancer: A Case Report With Seven Years of Follow-Up.
- Case Report, PC, NA
OS↑, Dose↝,
5796- MET,    Tumor, whole blood, plasma, and tissue concentrations of metformin in lung cancer patients
- Human, Lung, NA
selectivity↑, AMPK↑, Risk↓, Half-Life↝, ChemoSen↑,
5795- MET,    Metformin: A Review of Potential Mechanism and Therapeutic Utility Beyond Diabetes
- Review, AD, NA - Review, Park, NA - Review, Diabetic, NA
*AntiDiabetic↑, *AMPK↑, *glyC↓, *ROS↓, *cardioP↑, *neuroP↑, *Half-Life↝, *toxicity↝, *BioAv↑, *glucose↓, *AGEs↓, AntiCan↑, Risk↓, TumCP↓, Apoptosis↑, TumCCA↑, cycD1/CCND1↓, pRB↓, p27/CDKN1B↓, mTOR↓, Casp↑, ROS↑, MMP↓, ChemoSen↑, *hepatoP↑, *CRM↑, *Insulin↓,
5785- MET,    Metformin improves healthspan and lifespan in mice
- in-vivo, Nor, NA
*AntiDiabetic↑, *AntiAge↑, *toxicity⇅, *CRM↑, *Strength↑, *LDL↓, *AMPK↑, *TAC↑, *ROS↓, *Inflam↓, Risk↓, *cardioP↑, *ALAT↓, *NRF2↑, *SOD2↑, *TrxR1↑, *NQO1↑, *NQO2↑,
8705- MET,    Clinical pharmacokinetics of metformin
- Review, Nor, NA
*Half-Life↝, *other↝, *toxicity↝,
8562- MET,    Hexokinase 2 Depletion Confers Sensitization to Metformin and Inhibits Glycolysis in Lung Squamous Cell Carcinoma
- in-vitro, Lung, NA
Synergy↑,
2457- MET,    Metformin Impairs Glucose Consumption and Survival in Calu-1 Cells by Direct Inhibition of Hexokinase-II
- in-vitro, Lung, Calu-1
HK1↓, HK2↓, GlucoseCon↓, MMP↓, ATP↓,
8706- MET,    Why Metformin Should Not Be Used as an Oxidative Phosphorylation Inhibitor in Cancer Patients
- Review, Var, NA
OXPHOS↓, compI↓, ATP↝,
8707- MET,    Metformin in therapeutic applications in human diseases: its mechanism of action and clinical study
- Review, Var, NA - Review, AD, NA
*BioAv↝, *cardioP↑, *Obesity↓, *neuroP↑, *toxicity↝, *Dose↝, *GutMicro↑, *AMPK↑, *glucose↓, *NLRP3↑, *Inflam↓, *Stroke↓, *Cartilage↑, FOXP3↑, TumAuto↑, mTOR↓, PD-L1↓, RadioS↑, ChemoSen↑, ROS↓, OXPHOS↓, compI↓, Glycolysis↝, TumCP↓, *BioAv↝, *AntiAge↑, *SIRT1↑, *cognitive↑, *Risk↓, Ki-67↓, Synergy↝, PFS∅, OS∅,
8708- MET,    Tumour, whole-blood, plasma and tissue concentrations of metformin in lung cancer patients
- Human, Lung, NA
BioAv↓, BioAv↑, Half-Life↝, Dose↓, compI↓,
8709- MET,    Effect of Metformin vs Placebo on Invasive Disease–Free Survival in Patients With Breast Cancer
- Trial, BC, NA
Risk∅, Dose↝, OS∅,
8710- MET,    Does metformin reduce the risk of cancer in obesity and diabetes? A systematic review and meta-analysis
- Review, Var, NA
Risk∅,
8711- MET,    https://pubmed.ncbi.nlm.nih.gov/42725610/
- Review, Var, NA
PI3K↓, Akt↓, mTOR↓, OCR↑, Hypoxia↓, RadioS↑, ChemoSen↑,
8712- MET,    Metformin Active Surveillance Trial in Low-Risk Prostate Cancer
- Trial, Pca, NA
Dose↝, Risk∅, eff∅,
8713- MET,    Metformin for patients with metastatic prostate cancer starting androgen deprivation therapy: a randomised phase 3 trial of the STAMPEDE platform protocol
- Trial, Pca, NA
Dose↝, OS∅,
2379- MET,    Down‐regulation of PKM2 enhances anticancer efficiency of THP on bladder cancer
- in-vitro, Bladder, T24/HTB-9 - in-vitro, BC, UMUC3
PKM2↓, p‑STAT3↓, TumCG↓, Synergy↑, chemoP↑, AMPK↑,
970- MET,    Metformin suppresses HIF-1α expression in cancer-associated fibroblasts to prevent tumor-stromal cross talk in breast cancer
- in-vitro, BC, NA
CAFs/TAFs↝, p‑AMPK↑, PHDs↑, Hif1a↓, TumCI↓,
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↑,
1043- MET,  immuno,    Metformin reduces PD-L1 on tumor cells and enhances the anti-tumor immune response generated by vaccine immunotherapy
- in-vitro, Var, NA
Synergy↑, PD-L1↓, Ki-67↑, TIM-3↑, L-sel↑,
1066- MET,    Metformin increases PDH and suppresses HIF-1α under hypoxic conditions and induces cell death in oral squamous cell carcinoma
- in-vitro, SCC, NA
PDH↑, Hif1a↓, TumCMig↓, Casp3↑, P53∅,
1204- MET,    Metformin induces ferroptosis through the Nrf2/HO-1 signaling in lung cancer
- in-vitro, Lung, A549 - in-vitro, Lung, H1299
MDA↑, ROS↑, Iron↑, GSH↓, T-SOD↓, Catalase↓, GPx4↓, xCT/SLC7A11↓, NRF2↓, HO-1↓,
2371- MET,    The role of pyruvate kinase M2 in anticancer therapeutic treatments
- Review, Var, NA
ChemoSen↑, PKM2↓, Hif1a↓, EMT↓,
2374- MET,    Metformin Induces Apoptosis and Downregulates Pyruvate Kinase M2 in Breast Cancer Cells Only When Grown in Nutrient-Poor Conditions
- in-vitro, BC, MCF7 - in-vitro, BC, SkBr3 - in-vitro, BC, MDA-MB-231
eff↑, Apoptosis↑, Glycolysis↓, PKM2↓, mTOR↓, PARP↓,
2375- MET,    Metformin inhibits gastric cancer via the inhibition of HIF1α/PKM2 signaling
- in-vitro, GC, SGC-7901
tumCV↓, TumCI↓, TumCMig↓, Apoptosis↑, PARP↓, PI3K↓, Akt↓, Hif1a↓, PKM2↓, COX2/PTGS2↓,
2376- MET,    Metformin Inhibits Epithelial-to-Mesenchymal Transition of Keloid Fibroblasts via the HIF-1α/PKM2 Signaling Pathway
- in-vitro, Nor, NA
*Hif1a↓, *EMT↓, *p‑P70S6K↓, *PKM2↓,
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↓, P70S6K↓, mTOR↓, PKM2↓, Warburg↓, AMPK↑,
2378- MET,    Metformin inhibits epithelial-mesenchymal transition of oral squamous cell carcinoma via the mTOR/HIF-1α/PKM2/STAT3 pathway
- in-vitro, SCC, CAL27 - in-vivo, NA, NA
TumCP↓, TumCMig↓, TumCI↓, EMT↓, mTOR↓, Hif1a↓, PKM2↓, STAT3↓, E-cadherin↑, Vim↓, Snail↓, STAT3↓,
2493- MET,    Metformin Inhibits Gluconeogenesis by a Redox-Dependent Mechanism In Vivo
- in-vivo, Nor, NA
glucoNG↓, glucose↓,
2383- MET,    Activation of AMPK by metformin promotes renal cancer cell proliferation under glucose deprivation through its interaction with PKM2
- in-vitro, RCC, A498
AMPK↑, TumCP↓, eff↓, eff↑,
2384- MET,    Integration of metabolomics and transcriptomics reveals metformin suppresses thyroid cancer progression via inhibiting glycolysis and restraining DNA replication
- in-vitro, Thyroid, BCPAP - in-vivo, NA, NA - in-vitro, Thyroid, TPC-1
Glycolysis↓, OXPHOS↑, tumCV↓, TumCI↓, TumCMig↓, EMT↓, Apoptosis↑, TumCCA↑, LDHA↓, PKM2↓, IDH1↑, TumCG↓,
2385- MET,    Metformin activates chaperone-mediated autophagy and improves disease pathologies in an Alzheimer disease mouse model
- in-vitro, AD, H4 - in-vitro, NA, HEK293 - in-vivo, NA, NA - in-vitro, NA, SH-SY5Y
*HK2↓, *PKM2↓, *Dose↝, IKKα↑, memory↑, p‑Hsc70↑, APP↓,
2386- MET,    Mechanisms of metformin inhibiting cancer invasion and migration
- Review, Var, NA
OS↑, AMPK↑, EMT↓, TGF-β↓, mTOR↓, P70S6K↓, PKM2↓, Hif1a↓, ChemoSen↑,
2387- MET,  GEM,    Metformin Increases the Response of Cholangiocarcinoma Cells to Gemcitabine by Suppressing Pyruvate Kinase M2 to Activate Mitochondrial Apoptosis
- in-vitro, CCA, HCC9810
Synergy↑, tumCV↓, TumCMig↓, TumCI↓, Apoptosis↑, PKM2↓, PDHB↓,
2436- MET,    Metformin alleviates nickel-induced autophagy and apoptosis via inhibition of hexokinase-2, activating lipocalin-2, in human bronchial epithelial cells
- in-vitro, Nor, BEAS-2B
*HK2↓,
2456- MET,    Direct inhibition of hexokinase activity by metformin at least partially impairs glucose metabolism and tumor growth in experimental breast cancer
- in-vitro, BC, MDA-MB-231 - in-vivo, NA, NA
GlucoseCon↓, TumCG↓, HK2↓, p‑AMPK↑, TXNIP↓, *toxicity↓,

Showing Research Papers: 1 to 50 of 53
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* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 53

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

Catalase↓, 1,   GPx4↓, 1,   GSH↓, 1,   HO-1↓, 1,   Iron↑, 1,   MDA↑, 1,   NRF2↓, 1,   ROS↓, 1,   ROS↑, 7,   T-SOD↓, 1,   Trx↓, 1,   xCT/SLC7A11↓, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

compI↓, 5,   OCR↓, 1,   OCR↑, 2,   OXPHOS↓, 2,   OXPHOS↑, 1,   PDH↓, 1,   PDH↑, 2,   p‑PDH↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ACLY↓, 1,   AMP↑, 1,   AMPK↑, 7,   p‑AMPK↑, 2,   ATP↓, 3,   ATP↝, 1,   FASN↓, 1,   GLS↓, 1,   glucoNG↓, 2,   glucose↓, 1,   GlucoseCon↓, 2,   Glycolysis↓, 6,   Glycolysis↑, 2,   Glycolysis↝, 1,   HK1↓, 1,   HK2↓, 4,   IDH1↑, 1,   lactateProd↓, 4,   LDHA↓, 1,   NADPH↓, 1,   PDHB↓, 1,   PDK1 / PDPK1↓, 1,   PDKs↓, 1,   PFK↓, 1,   PKM2↓, 10,   Warburg↓, 2,  

Cell Death(tgid=5) ⓘ

AIF↑, 1,   Apoptosis↑, 12,   BAX↓, 1,   BAX↑, 1,   Bcl-2↓, 4,   BIM↑, 1,   Casp↑, 1,   Casp3↑, 2,   cl‑Casp3↑, 1,   Casp8↑, 1,   Casp9↑, 1,   Cyt‑c↑, 1,   MLKL↑, 1,   p‑MLKL↓, 1,   Necroptosis↑, 1,   RIP3↑, 1,   p‑RIP3↑, 1,   TumCD↓, 1,   TumCD↑, 2,   TumCD∅, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

Akt↓, 2,   p‑ERK↓, 1,   IKKα↑, 1,   mTOR↓, 7,   P70S6K↓, 2,   PI3K↓, 2,   STAT3↓, 2,   p‑STAT3↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

cMyc↓, 1,   tumCV↓, 4,  

Protein Folding & ER Stress(tgid=8) ⓘ

p‑Hsc70↑, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

LC3B↑, 1,   p62↑, 1,   TumAuto↑, 2,  

DNA Damage & Repair(tgid=10) ⓘ

DNA-PK↑, 1,   DNAdam↑, 2,   hTERT/TERT↓, 1,   P53↑, 1,   P53∅, 1,   p‑P53↑, 1,   PARP↓, 2,   p‑PARP↑, 1,   cl‑PARP↑, 3,   γH2AX↑, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

CDK2↓, 1,   CDK4↓, 1,   CDK6↓, 1,   cycD1/CCND1↓, 4,   cycE/CCNE↓, 1,   Ki-67↓, 1,   Ki-67↑, 1,   p27/CDKN1B↓, 1,   pRB↓, 1,   TumCCA↑, 3,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

CSCs↓, 1,   Ki-67↓, 1,   Ki-67↑, 1,   TumCG↓, 5,   TumCG↑, 1,   TumCP↓, 11,  

Migration(tgid=13) ⓘ

CAFs/TAFs↝, 1,   E-cadherin↑, 1,   EMT↓, 5,   L-sel↑, 1,   Snail↓, 1,   TGF-β↓, 1,   TumCI↓, 6,   TumCMig↓, 6,   TumMeta↓, 1,   TXNIP↓, 1,   Vim↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 1,   Hif1a↓, 8,   Hypoxia↓, 1,   PHDs↑, 1,  

Barriers & Transport(tgid=15) ⓘ

GLUT1↓, 1,   GLUT3↓, 1,   MMP↓, 4,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 1,   FOXP3↑, 1,   Imm↑, 1,   PD-L1↓, 2,   TIM-3↑, 1,  

Cellular Microenvironment(tgid=17) ⓘ

pH↝, 1,  

Protein Aggregation(tgid=19) ⓘ

APP↓, 1,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

ERα/ESR1↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 1,   BioAv↑, 1,   ChemoSen↑, 9,   DDS↑, 1,   Dose↓, 1,   Dose↝, 7,   Dose∅, 2,   eff↓, 2,   eff↑, 6,   eff∅, 1,   Half-Life↝, 2,   RadioS↑, 3,   selectivity↓, 1,   selectivity↑, 6,   Synergy↑, 12,   Synergy↝, 1,  

Clinical Biomarkers(tgid=22) ⓘ

ERα/ESR1↓, 1,   hTERT/TERT↓, 1,   LDH↓, 2,   PD-L1↓, 2,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1,   chemoP↑, 2,   hepatoP↑, 1,   memory↑, 1,   neuroP↑, 1,   NP/CIPN↓, 1,   OS↑, 2,   OS∅, 3,   PFS∅, 1,   Risk↓, 3,   Risk∅, 3,   toxicity↓, 1,   toxicity∅, 1,   TumVol↓, 1,   TumW↓, 2,  
Total Targets: 167

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

NQO1↑, 1,   NRF2↑, 1,   ROS↓, 2,   SOD2↑, 1,   TAC↑, 1,   TrxR1↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

Insulin↓, 1,   mitResp↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ALAT↓, 1,   AMPK↑, 5,   CRM↑, 2,   glucoNG↓, 2,   glucose↓, 4,   glyC↓, 1,   HK2↓, 2,   LDL↓, 1,   PKM2↓, 2,   SIRT1↑, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

p‑P70S6K↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

other↝, 1,  

Protein Folding & ER Stress(tgid=8) ⓘ

NQO2↑, 1,  

Migration(tgid=13) ⓘ

Cartilage↑, 1,   EMT↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

Hif1a↓, 1,  

Barriers & Transport(tgid=15) ⓘ

BBB↑, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

Inflam↓, 2,   NLRP3↑, 1,  

Protein Aggregation(tgid=19) ⓘ

AGEs↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↑, 1,   BioAv↝, 2,   Dose↝, 2,   eff↑, 1,   Half-Life↝, 2,  

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiAge↑, 2,   AntiDiabetic↑, 3,   cardioP↑, 3,   cognitive↑, 2,   hepatoP↑, 1,   neuroP↑, 2,   Obesity↓, 1,   Risk↓, 1,   Strength↑, 1,   Stroke↓, 1,   toxicity↓, 1,   toxicity⇅, 1,   toxicity↝, 3,   toxicity∅, 1,  

Infection & Microbiome(tgid=24) ⓘ

GutMicro↑, 1,  
Total Targets: 49

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#:11  Target#:%  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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