Database Query Results : , , ACLY

ACLY, ATP citrate lyase: Click to Expand ⟱
Source:
Type:
ACLY links energy metabolism provided by catabolic pathways to biosynthesis. ACLY, which has been found to be overexpressed in many cancers, converts citrate into acetyl-CoA and OAA.ATP citrate lyase exhibited upregulation in various tumours.
General Tumour Biomarker
•ACLY is a key enzyme in cancer metabolism.
•ACLY is involved in glucose and lipid metabolism.
•Many ACLY inhibitors were developed as anti-cancer agents.

ACLY is a key enzyme in cellular metabolism that converts citrate into acetyl‐CoA and oxaloacetate. Acetyl‐CoA is a substrate for lipid synthesis and protein acetylation, processes that are often upregulated in cancer cells to support rapid growth and proliferation.

ACLY is found overexpressed in many aggressive cancers. ACLY abundantly consumes citrate from nutrient catabolism (especially glucose and glutamine) to support protein acetylation and intense nucleotide and lipid synthesis. The significant decrease in cytosolic citrate appears to play a central role in cancer metabolism by enhancing the Warburg effect and activating the PI3K / AKT axis promoting ACLY activity in a feedback loop. Thus, the inhibition of factors regulating its expression (such as SREBP1) and its activation (such as AKT) could have an anti-proliferative effect.

Elevated ACLY expression has been observed in a number of cancers. In many studies, high levels of ACLY have been associated with more aggressive disease and poorer prognoses.

Natural ACLY Inhibitors
-Hydroxycitrate (HCA):(widely studied)
-EGCG
-Quercetin
-Resveratrol
-Luteolin
-Citrate
-Cucurbitacin B
-Emodin?
Scientific Papers found: Click to Expand⟱
289- ALA,  HCA,  EA,    Cancer Metabolism: Fasting Reset, the Keto-Paradox and Drugs for Undoing
- Analysis, NA, NA
ACLY↓,
1172- Ash,    Withaferin A Inhibits Fatty Acid Synthesis in Rat Mammary Tumors
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231 - in-vivo, NA, NA
FASN↓, ACLY↓, ACC1↓, CPT1A↓, SREBP1↓,
3166- Ash,    Exploring the Multifaceted Therapeutic Potential of Withaferin A and Its Derivatives
- Review, Var, NA
*p‑PPARγ↓, *cardioP↑, *AMPK↑, *BioAv↝, *Half-Life↝, *Half-Life↝, *Dose↑, *chemoPv↑, IL6↓, STAT3↓, ROS↓, OXPHOS↓, PCNA↓, LDH↓, AMPK↑, TumCCA↑, NOTCH3↓, Akt↓, Bcl-2↓, Casp3↑, Apoptosis↑, eff↑, NF-kB↓, CSCs↓, HSP90↓, PI3K↓, FOXO3↑, β-catenin/ZEB1↓, N-cadherin↓, EMT↓, FASN↓, ACLY↓, ROS↑, NRF2↑, HO-1↑, NQO1↑, JNK↑, mTOR↓, neuroP↑, *TNF-α↓, *IL1β↓, *IL6↓, *IL8↓, *IL18↓, RadioS↑, eff↑,
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↓,
1588- Citrate,    ATP citrate lyase (ACLY) inhibitors: An anti-cancer strategy at the crossroads of glucose and lipid metabolism
- Review, NA, NA
ACLY↓,
1587- Citrate,    ATP citrate lyase: A central metabolic enzyme in cancer
- Review, NA, NA
ACLY↓, other↓, PFK1↓, ATP↓, PFK2↓, Mcl-1↓, Casp3↑, Casp2↑, Casp9↑, IGF-1R↓, PI3K↓, Akt↓, p‑Akt↓, p‑ERK↓, PTEN↑, Snail↓, E-cadherin↑, ChemoSen↑,
1586- Citrate,    Extracellular Citrate Is a Trojan Horse for Cancer Cells
- in-vitro, Liver, HepG2
Dose?, ac‑H4↓, lipidDe↓, ACLY↓, selectivity↑, *ACLY∅, Glycolysis↓, NADH↓, OAA↑, other↑,
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?,
1590- Cuc,    ATP citrate lyase (ACLY) inhibitors: An anti-cancer strategy at the crossroads of glucose and lipid metabolism
- Review, NA, NA
ACLY↓,
1412- HCA,    Identification of ATP Citrate Lyase as a Positive Regulator of Glycolytic Function in Glioblastomas
- in-vitro, GBM, U87MG - in-vitro, GBM, LN229
ACLY↓, TumCMig↓,
1625- HCA,    In S. cerevisiae hydroxycitric acid antagonizes chronological aging and apoptosis regardless of citrate lyase
- Review, Nor, NA
CRM↑, ACLY↓, TumAuto↑, Inflam↓, TumCG↓, toxicity∅, lipoGen↓, *ROS↓, *OCR↓,
1589- HCA,    ATP citrate lyase (ACLY) inhibitors: An anti-cancer strategy at the crossroads of glucose and lipid metabolism
- Review, NA, NA
ACLY↓, eff↑,
1627- HCA,    Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance
- Review, Var, NA
ChemoSen↑, eff↑, ACLY↓, LC3‑Ⅱ/LC3‑Ⅰ↑,
1628- HCA,  ALA,    Addition of Hydroxy Citrate improves effect of ALA
- Review, Var, NA
ACLY↓, other↓, ROS↑, eff↑, PDKs↓,
1629- HCA,  Tam,    Hydroxycitric acid reverses tamoxifen resistance through inhibition of ATP citrate lyase
- in-vitro, BC, MCF-7
ACLY↓, eff↓, tumCV↓, eff↑, Casp3↑, BAX↑, Bcl-2↓,
1630- HCA,    Chemistry and biochemistry of (-)-hydroxycitric acid from Garcinia
- Review, NA, NA
ACLY↓, FASN↓, lipoGen↓, Weight↓,
1631- HCA,    An overview of the safety and efficacy of a novel, natural(-)-hydroxycitric acid extract (HCA-SX) for weight management
- Review, Obesity, NA
*ACLY↓, *toxicity∅, *Dose∅,
293- HCA,  Tam,    Hydroxycitric acid potentiates the cytotoxic effect of tamoxifen in MCF-7 breast cancer cells through inhibition of ATP citrate lyase
- in-vitro, BC, MCF-7
TumCG↓, Apoptosis↑, ACLY↓, ACC-α↓, Fas↓,
292- HCA,    Hydroxycitric Acid Inhibits Chronic Myelogenous Leukemia Growth through Activation of AMPK and mTOR Pathway
- in-vitro, AML, K562
ACLY↓, AMPK↑, mTOR↑, eIF2α↑, ATFs↑, TumCG↓,
1575- statins,  Citrate,    Inhibition of Lung Cancer Growth: ATP Citrate Lyase Knockdown and Statin Treatment Leads to Dual Blockade of Mitogen-Activated Protein Kinase (MAPK) and Phosphatidylinositol-3-Kinase (PI3K)/AKT Pathways
- in-vitro, NSCLC, A549
eff↑, HMG-CoA↓, eff↑, AntiTum↑, EGFR↓, eff↑, ROS↑, EMT↓, E-cadherin↑, MUC1↑, p‑ACLY↓, p‑Akt↓, eff↑,
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↓, FASN↓, ACLY↓, LDH↓, Glycolysis↓, Warburg↓, PDK1↓, GLUT1↓, LDHA↓, ECAR↓, PDH↑, eff↑,

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 21

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

HO-1↑, 1,   lipidDe↓, 1,   NADH↓, 1,   NQO1↑, 1,   NRF2↑, 1,   OXPHOS↓, 1,   ROS↓, 1,   ROS↑, 5,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 1,  

Core Metabolism/Glycolysis ⓘ

ACC-α↓, 1,   ACC1↓, 1,   ACLY↓, 19,   p‑ACLY↓, 1,   AMPK↑, 3,   citrate↓, 1,   cMyc↓, 1,   CPT1A↓, 1,   CRM↑, 1,   ECAR↓, 1,   FASN↓, 5,   FASN↑, 1,   FBPase↑, 1,   GLS↓, 1,   glucoNG↑, 1,   Glycolysis↓, 4,   HK2↓, 1,   HMG-CoA↓, 1,   LDH↓, 3,   LDHA↓, 1,   lipoGen↓, 2,   NADPH↓, 1,   OAA↑, 1,   PDH↓, 1,   PDH↑, 1,   PDK1↓, 1,   PDKs↓, 1,   PFK↓, 1,   PFK1↓, 2,   PFK2↓, 2,   PKM2↓, 1,   SREBP1↓, 1,   TCA↑, 1,   Warburg↓, 1,  

Cell Death ⓘ

Akt↓, 3,   p‑Akt↓, 2,   Apoptosis↑, 3,   BAX↓, 1,   BAX↑, 1,   Bcl-2↓, 3,   Bcl-xL↓, 1,   Casp2↑, 2,   Casp3↑, 4,   Casp8↑, 1,   Casp9↑, 2,   Fas↓, 1,   JNK↑, 1,   Mcl-1↓, 2,   TumCD↑, 1,  

Transcription & Epigenetics ⓘ

ac‑H4↓, 1,   other↓, 2,   other↑, 1,   tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

ATFs↑, 1,   eIF2α↑, 1,   HSP90↓, 1,  

Autophagy & Lysosomes ⓘ

LC3‑Ⅱ/LC3‑Ⅰ↑, 1,   TumAuto↑, 1,  

DNA Damage & Repair ⓘ

PCNA↓, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

CSCs↓, 1,   EMT↓, 2,   p‑ERK↓, 1,   FOXO3↑, 1,   IGF-1R↓, 2,   mTOR↓, 2,   mTOR↑, 1,   NOTCH3↓, 1,   PI3K↓, 3,   PTEN↑, 2,   STAT3↓, 1,   TumCG↓, 3,  

Migration ⓘ

E-cadherin↑, 2,   MUC1↑, 1,   N-cadherin↓, 1,   Snail↓, 1,   TumCMig↓, 1,   TumCP↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

EGFR↓, 1,   Hif1a↓, 1,  

Barriers & Transport ⓘ

GLUT1↓, 2,   GLUT3↓, 1,  

Immune & Inflammatory Signaling ⓘ

IL6↓, 1,   Inflam↓, 1,   NF-kB↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 3,   Dose?, 2,   Dose↑, 1,   eff↓, 1,   eff↑, 13,   RadioS↑, 1,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

EGFR↓, 1,   IL6↓, 1,   LDH↓, 3,  

Functional Outcomes ⓘ

AntiTum↑, 1,   neuroP↑, 1,   toxicity∅, 1,   Weight↓, 1,  
Total Targets: 110

Pathway results for Effect on Normal Cells:


NA, unassigned ⓘ

chemoPv↑, 1,  

Redox & Oxidative Stress ⓘ

ROS↓, 1,  

Mitochondria & Bioenergetics ⓘ

OCR↓, 1,  

Core Metabolism/Glycolysis ⓘ

ACLY↓, 1,   ACLY∅, 1,   AMPK↑, 1,   p‑PPARγ↓, 1,  

Immune & Inflammatory Signaling ⓘ

IL18↓, 1,   IL1β↓, 1,   IL6↓, 1,   IL8↓, 1,   TNF-α↓, 1,  

Drug Metabolism & Resistance ⓘ

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

Clinical Biomarkers ⓘ

IL6↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 1,   toxicity∅, 1,  
Total Targets: 19

Scientific Paper Hit Count for: ACLY, ATP citrate lyase
11 HydroxyCitric Acid
5 Citric Acid
2 Alpha-Lipoic-Acid
2 Ashwagandha(Withaferin A)
2 tamoxifen
1 Ellagic acid
1 Caffeic acid
1 Metformin
1 Cucurbitacin
1 statins
1 Vitamin C (Ascorbic Acid)
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#:2  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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