Database Query Results : , , TCA

TCA, Krebs/Tricarboxylic Acid Cycle: Click to Expand ⟱
Source:
Type: enzymes
Tricarboxylic Acid (TCA) cycle, also known as the Citric Acid cycle or Krebs cycle, is a key metabolic pathway that plays a central role in cellular energy production.
The TCA cycle is a series of chemical reactions that occur in the mitochondria and involve the breakdown of acetyl-CoA, a molecule produced from the breakdown of carbohydrates, fats, and proteins. The TCA cycle produces:
1. NADH and FADH2
2. ATP
3. GTP
Expression of TCA cycle enzymes is often downregulated in cancer cells.

Since cancer cells often exhibit rewired metabolism, including alterations in the use of the TCA cycle, researchers are exploring potential therapeutic interventions that target metabolic enzymes or pathways.
TCA cycle is essential for normal cellular metabolism, its role in cancer is multifaceted. Cancer cells often reprogram their metabolism—including the TCA cycle—to support rapid growth, adapt to hypoxia, and manage oxidative stress. Mutations in key TCA cycle enzymes generate oncometabolites that further contribute to cancer progression by disrupting normal cellular regulation.

Rather than saying the TCA cycle is globally over- or underexpressed in cancer, it is more accurate to say that cancer cells reprogram the cycle—with selective upregulation of parts important for biosynthesis and survival and mutations or downregulation of other parts—to best support their growth and survival in a challenging microenvironment.

Oncometabolites
-Some metabolites in the Krebs cycle, when accumulated to abnormal levels due to genetic mutations or enzyme deficiencies, are termed “oncometabolites” because they can promote tumorigenesis.
-Mutations in succinate dehydrogenase (SDH) can lead to accumulation of succinate.
-Mutations in fumarate hydratase (FH) result in an accumulation of fumarate.
-Mutations in isocitrate dehydrogenase (IDH1 and IDH2) result in a neomorphic enzyme activity that converts α-ketoglutarate (α-KG) to 2-hydroxyglutarate:
Scientific Papers found: Click to Expand⟱
5257- 3BP,    Tumor Energy Metabolism and Potential of 3-Bromopyruvate as an Inhibitor of Aerobic Glycolysis: Implications in Tumor Treatment
- Review, Var, NA
Glycolysis↓, mt-OXPHOS↓, HK2↓, Cyt‑c↑, Casp3↓, Bcl-2↓, Mcl-1↓, GAPDH↓, LDH↓, PDH↓, TCA↓, GlutaM↓, GSH↓, ATP↓, mitResp↓, ROS↑, ChemoSen↑, toxicity↝,
5173- Ash,  2DG,    Withaferin A inhibits lysosomal activity to block autophagic flux and induces apoptosis via energetic impairment in breast cancer cells
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231 - in-vitro, BC, MDA-MB-468 - in-vitro, BC, T47D
autoF↓, lysosome↓, TumAuto↑, p‑LDH↓, ATP↓, AMPK↑, eff↑, TumCG↓, CTSD↓, CTSB↓, CTSL↑, cl‑PARP1↑, LDHA↓, TCA↓,
3156- Ash,    Withaferin A: From ayurvedic folk medicine to preclinical anti-cancer drug
- Review, Var, NA
MAPK↑, p38↑, BAX↑, BIM↑, CHOP↑, ROS↑, DR5↑, Apoptosis↑, Ferroptosis↑, GPx4↓, BioAv↝, HSP90↓, RET↓, E6↓, E7↓, Akt↓, cMET↓, Glycolysis↓, TCA↓, NOTCH1↓, STAT3↓, AP-1↓, PI3K↓, eIF2α↓, HO-1↑, TumCCA↑, CDK1↓, *hepatoP↑, *GSH↑, *NRF2↑, Wnt↓, EMT↓, uPA↓, CSCs↓, Nanog↓, SOX2↓, CD44↓, lactateProd↓, Iron↑, NF-kB↓,
1593- Citrate,    Citrate Induces Apoptotic Cell Death: A Promising Way to Treat Gastric Carcinoma?
- in-vitro, GC, BGC-823 - in-vitro, GC, SGC-7901
PFK↓, Glycolysis↓, tumCV↓, cl‑Casp3↑, cl‑PARP↑, Apoptosis↑, ATP↓, ChemoSen↑, Mcl-1↓, glucoNG↑, FBPase↑, OXPHOS↓, TCA↓, β-oxidation↓, HK2↓, PDH↓, ROS↑,
1578- Citrate,    Understanding the Central Role of Citrate in the Metabolism of Cancer Cells and Tumors: An Update
- Review, Var, NA
TCA↑, FASN↑, Glycolysis↓, glucoNG↑, PFK1↓, PFK2↓, FBPase↑, TumCP↓, eff↑, ACLY↓, Dose↑, Casp3↑, Casp2↑, Casp8↑, Casp9↑, Bcl-xL↓, Mcl-1↓, IGF-1R↓, PI3K↓, Akt↓, mTOR↓, PTEN↑, ChemoSen↑, Dose?,
1576- Citrate,    Targeting citrate as a novel therapeutic strategy in cancer treatment
- Review, Var, NA
TCA↓, T-Cell↝, Glycolysis↓, PKM2↓, PFK2?, SDH↓, PDH↓, β-oxidation↓, CPT1A↓, FASN↑, Casp3↑, Casp2↑, Casp8↑, Casp9↑, cl‑PARP↑, Hif1a↓, GLUT1↓, angioG↓, Ca+2↓, ROS↓, eff↓, Dose↓, eff↑, Mcl-1↓, HK2↓, IGF-1R↓, PTEN↑, citrate↓, Dose∅, eff↑, eff↑, eff↑, eff↑,
1574- Citrate,    Citrate Suppresses Tumor Growth in Multiple Models through Inhibition of Glycolysis, the Tricarboxylic Acid Cycle and the IGF-1R Pathway
- in-vitro, Lung, A549 - in-vitro, Melanoma, WM983B - in-vivo, NA, NA
TumCG↓, eff↑, T-Cell↑, p‑IGF-1R↓, p‑Akt↓, PTEN↑, p‑eIF2α↑, OCR↓, ROS↓, ECAR∅, IL1↑, TNF-α↑, IL10↑, IGF-1R↓, eIF2α↑, PTEN↑, TCA↓, Glycolysis↓, selectivity↑, *toxicity∅, Dose∅,
933- CUR,  EP,    Effective electrochemotherapy with curcumin in MDA-MB-231-human, triple negative breast cancer cells: A global proteomics study
- in-vitro, BC, NA
Apoptosis↑, ALDOA↓, ENO2↓, LDHA↓, LDHB↓, PFKP↓, PGK1↓, PGM1↓, PGAM1↓, OXPHOS↑, TCA↑,
5205- Gallo,    Evaluation of the anti-tumor effects of lactate dehydrogenase inhibitor galloflavin in endometrial cancer cells
- in-vitro, Endo, ISH
LDH↓, TumCG↓, LDHA↓, Apoptosis↑, cl‑Casp3↑, Mcl-1↓, Bcl-2↓, TumCCA↑, ROS↑, mt-DNAdam↑, GlucoseCon↓, ATP↓, PDH↑, Pyruv↑, Glycolysis↓, TCA↑, cMyc↓, E-cadherin↑, Slug↓,
2247- MF,    Effects of Pulsed Electromagnetic Field Treatment on Skeletal Muscle Tissue Recovery in a Rat Model of Collagenase-Induced Tendinopathy: Results from a Proteome Analysis
- in-vivo, Nor, NA
*Glycolysis↓, *LDHB↑, *NAD↑, *ATP↑, *antiOx↑, *ROS↑, *YAP/TEAD↑, *PGC-1α↑, *TCA↑, *FAO↑, *OXPHOS↑,
2259- MFrot,  MF,    Method and apparatus for oncomagnetic treatment
- in-vitro, GBM, NA
MMP↓, Bcl-2↓, BAX↑, Bak↑, Cyt‑c↑, Casp3↑, Casp9↑, DNAdam↑, ROS↑, lactateProd↑, Apoptosis↑, MPT↑, *selectivity↑, eff↑, MMP↓, selectivity↑, TCA?, H2O2↑, eff↑, *antiOx↑, H2O2↑, eff↓, GSH/GSSG↓, *toxicity∅, OS↑,
5254- NCL,    The magic bullet: Niclosamide
- Review, Var, NA
Wnt↓, β-catenin/ZEB1↓, RAS↓, STAT3↓, NOTCH↓, E2Fs↓, mTOR↓, eff↑, PD-1↓, PD-L1↓, BioAv↝, toxicity↓, BioAv↑, ETC↑, NADH:NAD↓, TCA↑, Warburg↓, Diff↑, AMPK↑, P53↑, PP2A↑, HIF-1↓, KRAS↓, Myc↓, RadioS↑, ChemoSen↑, Dose↝, Dose↑,
119- UA,  CUR,  RES,    Combinatorial treatment with natural compounds in prostate cancer inhibits prostate tumor growth and leads to key modulations of cancer cell metabolism
- in-vitro, Pca, DU145 - in-vitro, Pca, PC3
ROS⇅, p‑STAT3↓, Src↓, AMPK↑, GlutMet↑, TCA↑, glut↓,
630- VitC,    Metabolomic alterations in human cancer cells by vitamin C-induced oxidative stress
- in-vitro, BC, MCF-7 - in-vitro, BC, HT-29
TCA↑, ATP↓, NAD↓, H2O2↑, GSH/GSSG↓,
1214- VitK2,    Vitamin K2 promotes PI3K/AKT/HIF-1α-mediated glycolysis that leads to AMPK-dependent autophagic cell death in bladder cancer cells
- in-vitro, Bladder, T24/HTB-9 - in-vitro, Bladder, J82
Glycolysis↑, GlucoseCon↑, lactateProd↑, TCA↓, PI3K↑, Akt↑, AMPK↑, mTORC1↓, TumAuto↑, GLUT1↑, HK2↑, LDHA↑, ACC↓, PDH↓, eff↓, cMyc↓, Hif1a↑, p‑Akt↑, eff↓, eff↓, eff↓, eff↓, ROS↑,

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 15

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Ferroptosis↑, 1,   GPx4↓, 1,   GSH↓, 1,   GSH/GSSG↓, 2,   H2O2↑, 3,   HO-1↑, 1,   Iron↑, 1,   OXPHOS↓, 1,   OXPHOS↑, 1,   mt-OXPHOS↓, 1,   ROS↓, 2,   ROS↑, 6,   ROS⇅, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 5,   ETC↑, 1,   mitResp↓, 1,   MMP↓, 2,   MPT↑, 1,   OCR↓, 1,   SDH↓, 1,  

Core Metabolism/Glycolysis ⓘ

ACC↓, 1,   ACLY↓, 1,   ALDOA↓, 1,   AMPK↑, 4,   citrate↓, 1,   cMyc↓, 2,   CPT1A↓, 1,   ECAR∅, 1,   ENO2↓, 1,   FASN↑, 2,   FBPase↑, 2,   GAPDH↓, 1,   glucoNG↑, 2,   GlucoseCon↓, 1,   GlucoseCon↑, 1,   glut↓, 1,   GlutaM↓, 1,   GlutMet↑, 1,   Glycolysis↓, 7,   Glycolysis↑, 1,   HK2↓, 3,   HK2↑, 1,   lactateProd↓, 1,   lactateProd↑, 2,   LDH↓, 2,   p‑LDH↓, 1,   LDHA↓, 3,   LDHA↑, 1,   LDHB↓, 1,   NAD↓, 1,   NADH:NAD↓, 1,   PDH↓, 4,   PDH↑, 1,   PFK↓, 1,   PFK1↓, 1,   PFK2?, 1,   PFK2↓, 1,   PFKP↓, 1,   PGAM1↓, 1,   PGK1↓, 1,   PGM1↓, 1,   PKM2↓, 1,   Pyruv↑, 1,   TCA?, 1,   TCA↓, 7,   TCA↑, 6,   Warburg↓, 1,   β-oxidation↓, 2,  

Cell Death ⓘ

Akt↓, 2,   Akt↑, 1,   p‑Akt↓, 1,   p‑Akt↑, 1,   Apoptosis↑, 5,   Bak↑, 1,   BAX↑, 2,   Bcl-2↓, 3,   Bcl-xL↓, 1,   BIM↑, 1,   Casp2↑, 2,   Casp3↓, 1,   Casp3↑, 3,   cl‑Casp3↑, 2,   Casp8↑, 2,   Casp9↑, 3,   Cyt‑c↑, 2,   DR5↑, 1,   Ferroptosis↑, 1,   MAPK↑, 1,   Mcl-1↓, 5,   Myc↓, 1,   p38↑, 1,  

Kinase & Signal Transduction ⓘ

RET↓, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   eIF2α↓, 1,   eIF2α↑, 1,   p‑eIF2α↑, 1,   HSP90↓, 1,  

Autophagy & Lysosomes ⓘ

autoF↓, 1,   lysosome↓, 1,   TumAuto↑, 2,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   mt-DNAdam↑, 1,   P53↑, 1,   cl‑PARP↑, 2,   cl‑PARP1↑, 1,  

Cell Cycle & Senescence ⓘ

CDK1↓, 1,   E2Fs↓, 1,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

CD44↓, 1,   cMET↓, 1,   CSCs↓, 1,   CTSB↓, 1,   CTSD↓, 1,   CTSL↑, 1,   Diff↑, 1,   EMT↓, 1,   IGF-1R↓, 3,   p‑IGF-1R↓, 1,   mTOR↓, 2,   mTORC1↓, 1,   Nanog↓, 1,   NOTCH↓, 1,   NOTCH1↓, 1,   PI3K↓, 2,   PI3K↑, 1,   PTEN↑, 4,   RAS↓, 1,   SOX2↓, 1,   Src↓, 1,   STAT3↓, 2,   p‑STAT3↓, 1,   TumCG↓, 3,   Wnt↓, 2,  

Migration ⓘ

AP-1↓, 1,   Ca+2↓, 1,   E-cadherin↑, 1,   KRAS↓, 1,   Slug↓, 1,   TumCP↓, 1,   uPA↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   HIF-1↓, 1,   Hif1a↓, 1,   Hif1a↑, 1,  

Barriers & Transport ⓘ

GLUT1↓, 1,   GLUT1↑, 1,  

Immune & Inflammatory Signaling ⓘ

IL1↑, 1,   IL10↑, 1,   NF-kB↓, 1,   PD-1↓, 1,   PD-L1↓, 1,   T-Cell↑, 1,   T-Cell↝, 1,   TNF-α↑, 1,  

Protein Aggregation ⓘ

PP2A↑, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 1,   BioAv↝, 2,   ChemoSen↑, 4,   Dose?, 1,   Dose↓, 1,   Dose↑, 2,   Dose↝, 1,   Dose∅, 2,   eff↓, 7,   eff↑, 11,   RadioS↑, 1,   selectivity↑, 2,  

Clinical Biomarkers ⓘ

E6↓, 1,   E7↓, 1,   KRAS↓, 1,   LDH↓, 2,   p‑LDH↓, 1,   Myc↓, 1,   PD-L1↓, 1,  

Functional Outcomes ⓘ

OS↑, 1,   toxicity↓, 1,   toxicity↝, 1,  
Total Targets: 179

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   GSH↑, 1,   NRF2↑, 1,   OXPHOS↑, 1,   ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↑, 1,   PGC-1α↑, 1,  

Core Metabolism/Glycolysis ⓘ

FAO↑, 1,   Glycolysis↓, 1,   LDHB↑, 1,   NAD↑, 1,   TCA↑, 1,  

Cell Death ⓘ

YAP/TEAD↑, 1,  

Drug Metabolism & Resistance ⓘ

selectivity↑, 1,  

Functional Outcomes ⓘ

hepatoP↑, 1,   toxicity∅, 2,  
Total Targets: 16

Scientific Paper Hit Count for: TCA, Krebs/Tricarboxylic Acid Cycle
4 Citric Acid
2 Ashwagandha(Withaferin A)
2 Curcumin
2 Magnetic Fields
1 3-bromopyruvate
1 2-DeoxyGlucose
1 Electrical Pulses
1 Galloflavin
1 Magnetic Field Rotating
1 Niclosamide (Niclocide)
1 Ursolic acid
1 Resveratrol
1 Vitamin C (Ascorbic Acid)
1 Vitamin K2
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#:818  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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