GLS Cancer Research Results

GLS, Glutaminase: Click to Expand ⟱
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GLS - Glutaminase

Abbreviation: GLS, GLS1, Kidney-Type Glutaminase

Alternative Names: KGA, GAC

Type: Mitochondrial metabolic enzyme / glutamine metabolism enzyme / glutaminolysis regulator

Function: GLS catalyzes the conversion of glutamine to glutamate and ammonia, providing the first major enzymatic step of glutaminolysis. Glutamate can subsequently be converted to α-ketoglutarate to replenish the TCA cycle and can also support glutathione synthesis, amino-acid metabolism, nucleotide synthesis, lipid synthesis, and cellular redox control.

Cancer: ↑ GLS expression and activity are increased in many cancers and support glutamine-dependent proliferation, energy production, anabolic metabolism, redox homeostasis, survival, and treatment resistance.

Favorable Direction in Cancer: ↓ GLS expression or activity is generally favorable in glutamine-dependent cancers and can reduce glutaminolysis, TCA-cycle replenishment, glutathione production, and cancer-cell survival.

Pathway Relationship: GLS ↑ → glutaminolysis ↑ → glutamate ↑ → α-ketoglutarate/TCA-cycle anaplerosis ↑ and glutathione synthesis ↑.

Interpretation Note: GLS should be distinguished from GLS2. GLS generally has a stronger tumor-promoting association, whereas GLS2 can function as either a tumor promoter or tumor suppressor depending on cancer type.
Scientific Papers found: Click to Expand⟱
2618- Ba,    Baicalein induces apoptosis by inhibiting the glutamine-mTOR metabolic pathway in lung cancer
- in-vitro, Lung, H1299 - in-vivo, Lung, A549
TumCG↓, Baicalein inhibited lung cancer xenograft tumor growth in vivo and suppressed proliferation and promoted apoptosis in lung cancer cells in vitro.
TumCP↓,
Apoptosis↑,
GLUT1↓, baicalein interacted with glutamine transporters as well as glutaminase and inhibited their activation
GLS↓,
mTOR↓, mTOR, an apoptosis-related protein and downstream target of glutamine metabolism, was also inhibited by baicalein treatment
*toxicity∅, baicalein treatment did not result in damage to the mouse organs, including the liver, heart, spleen, lung, or kidney
cl‑Casp9↓, baicalein dose-dependently suppressed the protein levels of Bax, cleaved caspase 9, and cleaved caspase 3 in H1299 and A549 cells
cl‑Casp3↓,
GSH↓, Meanwhile, the levels of glutathione (GSH), S-formylglutathione, and pyroglutamic acid in baicalein-treated A549 cells were downregulated when compared to that in control group
GlutMet↓, These findings indicate that baicalein inhibits cellular glutamine uptake, which is consistent with the findings of metabolomics studies.

2706- BBR,    Berberine Inhibits Growth of Liver Cancer Cells by Suppressing Glutamine Uptake
- in-vitro, HCC, Hep3B - in-vitro, HCC, Bel-7402 - in-vivo, NA, NA
TumCP↓, Berberine inhibited the proliferation of Hep3B and BEL-7404 cell in vitro
glut↓, Berberine suppressed the glutamine uptake by inhibiting SLC1A5.
SLC12A5↓,
cMyc↓, Berberine suppresses SLC1A5 expression by inhibiting c-Myc
GLS↓, The expression of SLC1A5, GLS and PSPH decreased, and such decrease was enhanced with the increase in berberine dose

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↓, downregulation of Glutaminase (GLS) and Malic Enzyme 1 (ME1)
NADPH↓, CA alone and co-treated with Met caused significant reduction of NADPH
ROS↑, increased ROS formation and enhanced cell death
TumCD↑,
AMPK↑, activation of AMPK
Hif1a↓, Met inhibited Hypoxia-inducible Factor 1 (HIF-1α). CA treatment at 100 μM for 24 h also inhibited HIF-1α
GLUT1↓,
GLUT3↓,
HK2↓,
PFK↓, PFKFB4
PKM2↓,
LDH↓,
cMyc↓, Met suppressed the expression of c-Myc, BAX and cyclin-D1 (CCND1) a
BAX↓,
cycD1/CCND1↓,
PDH↓, CA at a concentration of 100 µM caused inhibition of PDK activity
ROS↑, CA Regulates TCA Cycle Supply via Pyruvate Dehydrogenase Complex (PDH), Induces Mitochondrial ROS Generation and Evokes Apoptosis
Apoptosis↑,
eff↑, both drugs inhibited the expression of ACLY and FAS, but the greatest effect was detected after co-treatment
ACLY↓,
FASN↓,
Bcl-2↓,
Glycolysis↓, Met acts as a glycolytic inhibitor under normoxic and hypoxic conditions

6223- CUR,    Curcumin Rewires the Tumor Metabolic Landscape: Mechanisms and Clinical Prospects
- Review, Var, NA
Ferroptosis↑, including the induction of ferroptosis by regulating the SLC7A11/GPX4 axis
GutMicro↑, and modulating gut microbiota metabolism. I
Akt↓, it inhibits pro-tumorigenic signals such as Akt/mTOR, NF-κB, Wnt/β-catenin, and STAT3, thereby blocking tumor proliferation, invasion, and metastasis
mTOR↓,
NF-kB↓,
Wnt↓,
β-catenin/ZEB1↓,
STAT3↓,
TumCP↓,
TumCI↓,
TumMeta↓,
AMPK↑, activates tumor-suppressive and cytoprotective pathways, including AMPK, p53, and nuclear factor erythroid 2-related factor 2 (Nrf2), which induce cell cycle arrest and apoptosis
P53↑,
NRF2↑,
TumCCA↑,
Apoptosis↑,
Casp↑, activation of the Caspase cascade
GPx4↓, as well as ferroptosis by inhibiting the solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) axis [5]
DNMTs↓, inhibiting epigenetic regulatory mechanisms such as DNMTs and HDACs.
HDAC↓,
VEGF↓, inhibiting VEGF signaling and enhances the immune microenvironment by improving T cell and NK cell function
Imm↑,
NK cell↑,
Warburg↓, Curcumin effectively reverses the Warburg effect and interferes with glucose metabolism by targeting HIF-1α and inhibiting key enzymes, including hexokinase 2 (HK2), pyruvate kinase M2 (PKM2), and lactate dehydrogenase A (LDHA)
Hif1a↓,
HK2↓,
PKM2↓,
LDHA↓,
GLUT1↓, as well as the functions of glucose transporter 1 (GLUT1) and monocarboxylate transporters (MCTs) [12].
MCT1↓,
AMPK↑, curcumin activates signaling pathways such as AMPK, downregulates fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD1),
FASN↓,
SCD1↓,
GLS↓, Curcumin extensively intervenes in amino acid metabolism by inhibiting the activity of glutaminase (GLS), ornithine decarboxylase (ODC), and other enzymes,
Apoptosis↑, inducing apoptosis through mechanisms such as disrupting the electron transport chain, reducing membrane potential, and promoting the generation of reactive oxygen species (ROS)
ETC↓,
MMP↓,
ROS↑,
lipid-P↑, curcumin induces lipid peroxidation and collapses redox homeostasis, thereby activating the ferroptosis program [
ChemoSen↑, blocking invasion and metastasis, and enhancing chemosensitivity.
PDK1 / PDPK1↓, In hypoxic pancreatic cancer cells, curcumin downregulates the expression of GLUT1, HK2, LDHA, and PDK1 by inhibiting the Beclin1/HIF-1α axis, which results in reduced ATP production and inhibited cell proliferation [
Beclin-1/ATG6↓,
ATP↓,
Glycolysis↓, inhibiting glycolysis
GlucoseCon↓, decreased glucose uptake and increased lactate production
lactateProd↑,
MMPs↓, reduces MMP, GSH, and G6PD activities
GSH↓, inhibition of SLC7A11 to limit GSH synthesis, thereby triggering the collapse of the antioxidant defense system
G6PD↓,
OXPHOS↓, downregulate OXPHOS and glycolysis activities
SREBP2↓, curcumin treatment leads to a marked downregulation of the mRNA expression of SREBP and its target genes. inhibiting the expression of NPC1L1, SREBP-2, and HNF1α
COX2/PTGS2↓, curcumin exerts anti-tumor effects by downregulating the expression of NF-κB, COX-2, and AP-1
AP-1↓,
NADH↓, decreased GPx4 and FSP1 expression, induced ferroptosis by inhibiting GSH-GPx4 and FSP1-CoQ 10-NADH pathways
NRF2↑, it inhibits GPX4 and activates Nrf2 and heme oxygenase-1 (HO-1). This results in an abnormal accumulation of intracellular Fe2+, ROS, lipid peroxides, and malondialdehyde (MDA), along with a depletion of GSH
HO-1↑,
Iron↑,
MDA↑,
*ROS↓, studies have demonstrated that the topical application of curcumin on the skin exerts antitumor effects by synergistically downregulating COX-2 and ODC activities, alleviating oxidative damage, and concurrently inhibiting inflammatory proliferation i
*Inflam↓,

975- Est,    Estrogen inhibits autophagy and promotes growth of endometrial cancer by promoting glutamine metabolism
- vitro+vivo, UEC, NA
GLS↑, in estrogen-sensitive UEC cell (UECC) (an ER inhibitor antagonist) could reverse these effects.
cMyc↑, three MYC subtypes (c-MYC, n-MYC and l-MYC) were increased after estrogen treatment
GlutMet↑,
tumCV↑,
TumAuto↓,

8281- LE,    A Licorice Roots Extract Induces Apoptosis and Cell Cycle Arrest and Improves Metabolism via Regulating MiRNAs in Liver Cancer Cells
- in-vitro, Liver, NA
Apoptosis↑, Our data showed various beneficial effects of licorice roots extract including induction of apoptosis and cell cycle arrest.
TumCCA↑,
Let-7↑, upregulating tumor suppressor miRNAs; let7a-3p, miR-34c-5p, miR-122-5p, miR-126-3p, miR195-5p, miR-199a-5p, miR-206, and miR-326-5p
miR-34b-5p↑,
miR-122-5p↑,
miR-126↑,
miR-195↑,
miR-199↑,
miR-206↑,
miR-326-5p↑,
Hif1a↓, inhibiting HIF1α, PI3K and C-Myc and activating AMPK and p53.
PI3K↓,
cMyc↓,
AMPK↑,
P53↑,
Glycolysis↓, inhibiting enzymes of glycolysis; HK-2, LDH-A and PK-M2; pentose phosphate pathway; G6PD and glutaminolysis; glutaminase.
HK2↓,
LDHA↓,
PKM2↓,
PPP↓,
G6PD↓,
GlutaM↓,
GLS↓,
miR-21↑, However, such an extract upregulated oncogenic miRNAs; miR-21, miR-221, and miR-222.
miR-221↑, Although the present data highlights the ability of licorice roots extract to enhance apoptosis and cell cycle arrest and correct altered metabolism, it warns against its unfavorable effects
miR-222↑,


Showing Research Papers: 1 to 6 of 6

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 6

Pathway results for Effect on Cancer / Diseased Cells:


NA, unassigned(tgid=0) ⓘ

miR-122-5p↑, 1,   miR-195↑, 1,   miR-199↑, 1,   miR-326-5p↑, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

Ferroptosis↑, 1,   GPx4↓, 1,   GSH↓, 2,   HO-1↑, 1,   Iron↑, 1,   lipid-P↑, 1,   MDA↑, 1,   NADH↓, 1,   NRF2↑, 2,   OXPHOS↓, 1,   ROS↑, 3,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↓, 1,   ETC↓, 1,   MMP↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ACLY↓, 1,   AMPK↑, 4,   cMyc↓, 3,   cMyc↑, 1,   FASN↓, 2,   G6PD↓, 2,   GLS↓, 5,   GLS↑, 1,   GlucoseCon↓, 1,   glut↓, 1,   GlutaM↓, 1,   GlutMet↓, 1,   GlutMet↑, 1,   Glycolysis↓, 3,   HK2↓, 3,   lactateProd↑, 1,   LDH↓, 1,   LDHA↓, 2,   NADPH↓, 1,   PDH↓, 1,   PDK1 / PDPK1↓, 1,   PFK↓, 1,   PKM2↓, 3,   PPP↓, 1,   SCD1↓, 1,   SREBP2↓, 1,   Warburg↓, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 1,   Apoptosis↑, 5,   BAX↓, 1,   Bcl-2↓, 1,   Casp↑, 1,   cl‑Casp3↓, 1,   cl‑Casp9↓, 1,   Ferroptosis↑, 1,   MCT1↓, 1,   TumCD↑, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

miR-21↑, 1,   tumCV↑, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

Beclin-1/ATG6↓, 1,   TumAuto↓, 1,  

DNA Damage & Repair(tgid=10) ⓘ

DNMTs↓, 1,   P53↑, 2,  

Cell Cycle & Senescence(tgid=11) ⓘ

cycD1/CCND1↓, 1,   TumCCA↑, 2,  

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

HDAC↓, 1,   Let-7↑, 1,   mTOR↓, 2,   PI3K↓, 1,   STAT3↓, 1,   TumCG↓, 1,   Wnt↓, 1,  

Migration(tgid=13) ⓘ

AP-1↓, 1,   miR-206↑, 1,   miR-221↑, 1,   miR-222↑, 1,   MMPs↓, 1,   TumCI↓, 1,   TumCP↓, 3,   TumMeta↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

Hif1a↓, 3,   miR-126↑, 1,   miR-34b-5p↑, 1,   VEGF↓, 1,  

Barriers & Transport(tgid=15) ⓘ

GLUT1↓, 3,   GLUT3↓, 1,   SLC12A5↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 1,   Imm↑, 1,   NF-kB↓, 1,   NK cell↑, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

ChemoSen↑, 1,   eff↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

GutMicro↑, 1,   LDH↓, 1,  
Total Targets: 94

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

ROS↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

Inflam↓, 1,  

Functional Outcomes(tgid=23) ⓘ

toxicity∅, 1,  
Total Targets: 3

Scientific Paper Hit Count for: GLS, Glutaminase
1 Baicalein
1 Berberine
1 Caffeic acid
1 Metformin
1 Curcumin
1 Estrogen
1 Licorice
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

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