Database Query Results : Metformin, ,

MET, Metformin: Click to Expand ⟱
Features: oral antidiabetic agent,
Metformin is a pleiotropic drug: attributed to its action on AMPK
Metformin directly 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.

-known as OXPHOS inhibitor
Scientific Papers found: Click to Expand⟱
291- ALA,  HCA,  MET,  Dicl,    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↑, eff↑, 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↓,
1864- DCA,  MET,    Dichloroacetate Enhances Apoptotic Cell Death via Oxidative Damage and Attenuates Lactate Production in Metformin-Treated Breast Cancer Cells
- in-vitro, BC, MCF-7 - in-vitro, BC, T47D - in-vitro, Nor, MCF10
PDKs↓, eff↑, ROS↑, PDK1↓, lactateProd↓, p‑PDH↑, Dose∅, OCR↑, DNA-PK↑, γH2AX↑, cl‑PARP↑, selectivity↑, *toxicity∅,
1866- DCA,  MET,  BTZ,    Targeting metabolic pathways alleviates bortezomib-induced neuropathic pain without compromising anticancer efficacy in a sex-specific manner
- in-vivo, NA, NA
eff↑, TumCG↓, Hif1a↓, PDH↑, lactateProd↓, TumVol↓, TumW↓, Glycolysis↑, neuroP↑,
1868- DCA,  MET,    Long-term stabilization of stage 4 colon cancer using sodium dichloroacetate therapy
- Case Report, NA, NA
eff↑, toxicity∅, MMP↓, Apoptosis↑, selectivity↑, pH↝, Dose↝, Dose↝, eff↑,
1154- HNK,  MET,    Honokiol inhibits the growth of hormone-resistant breast cancer cells: its promising effect in combination with metformin
- in-vitro, BC, MCF-7 - in-vitro, BC, SkBr3 - in-vitro, BC, MDA-MB-231
cl‑PARP↑, Bcl-2↓, ERα/ESR1↓,
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↑,
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↓,
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
eff↑, 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↓,
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↓,
2491- MET,    Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase
- in-vivo, Nor, NA
*glucoNG↓, *glucose↓, *mitResp↓,
2492- MET,    The Metformin Mechanism on Gluconeogenesis and AMPK Activation: The Metabolite Perspective
- Review, Nor, NA
*glucose↓, *glucoNG↓, *AMPK↑,
2493- MET,    Metformin Inhibits Gluconeogenesis by a Redox-Dependent Mechanism In Vivo
- in-vivo, Nor, NA
glucoNG↓, glucose↓,
2379- MET,    Down‐regulation of PKM2 enhances anticancer efficiency of THP on bladder cancer
- in-vitro, Bladder, T24 - in-vitro, BC, UMUC3
PKM2↓, p‑STAT3↓, TumCG↓, eff↑, chemoP↑, 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↓,
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↑,
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↓,
2374- MET,    Metformin Induces Apoptosis and Downregulates Pyruvate Kinase M2 in Breast Cancer Cells Only When Grown in Nutrient-Poor Conditions
- in-vitro, BC, MCF-7 - in-vitro, BC, SkBr3 - in-vitro, BC, MDA-MB-231
eff↑, Apoptosis↑, Glycolysis↓, PKM2↓, mTOR↓, PARP↓,
2371- MET,    The role of pyruvate kinase M2 in anticancer therapeutic treatments
- Review, Var, NA
ChemoSen↑, PKM2↓, Hif1a↓, EMT↓,
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↓, NRF2↓, HO-1↓,
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∅,
1043- MET,  immuno,    Metformin reduces PD-L1 on tumor cells and enhances the anti-tumor immune response generated by vaccine immunotherapy
- in-vitro, NA, NA
eff↑, PD-L1↓, Ki-67↑, TIM-3↑, L-sel↑,
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↑,
970- MET,    Metformin suppresses HIF-1α expression in cancer-associated fibroblasts to prevent tumor-stromal cross talk in breast cancer
CAFs/TAFs↝, p‑AMPK↑, PHDs↑, Hif1a↓, TumCI↓,

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 30

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Catalase↓, 1,   GPx4↓, 1,   GSH↓, 1,   HK1↓, 1,   HO-1↓, 1,   Iron↑, 1,   MDA↑, 1,   NRF2↓, 1,   OXPHOS↑, 1,   ROS↑, 5,   T-SOD↓, 1,   xCT↓, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 1,   ATP↓, 2,   MMP↓, 3,   OCR↑, 1,  

Core Metabolism/Glycolysis ⓘ

ACLY↓, 1,   AMPK↑, 6,   p‑AMPK↑, 2,   cMyc↓, 1,   FASN↓, 1,   GLS↓, 1,   glucoNG↓, 1,   glucose↓, 1,   GlucoseCon↓, 2,   Glycolysis↓, 4,   Glycolysis↑, 1,   HK2↓, 4,   IDH1↑, 1,   lactateProd↓, 2,   LDH↓, 1,   LDHA↓, 1,   NADPH↓, 1,   PDH↓, 1,   PDH↑, 2,   p‑PDH↑, 1,   PDHB↓, 1,   PDK1↓, 1,   PDKs↓, 1,   PFK↓, 1,   PKM2↓, 10,   Warburg↓, 2,  

Cell Death ⓘ

Akt↓, 1,   Apoptosis↑, 8,   BAX↓, 1,   BAX↑, 1,   Bcl-2↓, 3,   BIM↑, 1,   Casp3↑, 2,   Casp8↑, 1,   Casp9↑, 1,   Cyt‑c↑, 1,   MLKL↑, 1,   p‑MLKL↓, 1,   Necroptosis↑, 1,   TumCD↑, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 4,  

Protein Folding & ER Stress ⓘ

p‑Hsc70↑, 1,  

Autophagy & Lysosomes ⓘ

LC3B↑, 1,   p62↑, 1,   TumAuto↑, 1,  

DNA Damage & Repair ⓘ

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

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 5,   mTOR↓, 4,   P70S6K↓, 2,   PI3K↓, 1,   STAT3↓, 2,   p‑STAT3↓, 1,   TumCG↓, 5,   TumCG↑, 1,  

Migration ⓘ

APP↓, 1,   CAFs/TAFs↝, 1,   E-cadherin↑, 1,   Ki-67↑, 1,   L-sel↑, 1,   RIP3↑, 1,   p‑RIP3↑, 1,   Snail↓, 1,   TGF-β↓, 1,   TumCI↓, 5,   TumCMig↓, 5,   TumCP↓, 2,   TXNIP↓, 1,   Vim↓, 1,  

Angiogenesis & Vasculature ⓘ

Hif1a↓, 8,   PHDs↑, 1,  

Barriers & Transport ⓘ

GLUT1↓, 1,   GLUT3↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IKKα↑, 1,   PD-L1↓, 1,  

Cellular Microenvironment ⓘ

pH↝, 1,   TIM-3↑, 1,  

Hormonal & Nuclear Receptors ⓘ

ERα/ESR1↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 2,   Dose↝, 2,   Dose∅, 2,   eff↓, 2,   eff↑, 11,   selectivity↓, 1,   selectivity↑, 4,  

Clinical Biomarkers ⓘ

ERα/ESR1↓, 1,   Ki-67↑, 1,   LDH↓, 1,   PD-L1↓, 1,  

Functional Outcomes ⓘ

chemoP↑, 1,   memory↑, 1,   neuroP↑, 1,   OS↑, 1,   toxicity∅, 1,   TumVol↓, 1,   TumW↓, 2,  
Total Targets: 122

Pathway results for Effect on Normal Cells:


Mitochondria & Bioenergetics ⓘ

mitResp↓, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   glucoNG↓, 2,   glucose↓, 2,   HK2↓, 2,   PKM2↓, 2,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 1,   p‑P70S6K↓, 1,  

Angiogenesis & Vasculature ⓘ

Hif1a↓, 1,  

Drug Metabolism & Resistance ⓘ

Dose↝, 1,  

Functional Outcomes ⓘ

toxicity↓, 1,   toxicity∅, 1,  
Total Targets: 12

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#:%
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