GlutaM Cancer Research Results

GlutaM, Glutaminolysis: Click to Expand ⟱
Source:
Type:
Glutaminolysis is the metabolic process through which glutamine, a non-essential amino acid, is catabolized to support cellular energy and biosynthesis. In many cancer cells, glutaminolysis is upregulated to meet the high demands for energy (ATP), biosynthetic precursors, and maintenance of redox balance.
Key Steps and Abbreviations in Glutaminolysis.
Glutamine (Gln): uptake of glutamine from the extracellular environment.
Glutaminase (GLS):Converts glutamine into glutamate by deamination. GLS overexpressed in cancers.
Glutamate (Glu): further converted into α-ketoglutarate (α-KG).
Glutamate Dehydrogenase (GDH): Catalyzes the conversion of glutamate to α-KG, feeding the tricarboxylic acid cycle (TCA, also known as Krebs cycle).
α-Ketoglutarate (α-KG):α-KG is a key intermediate in the TCA cycle.
Additional Players:
c-Myc: A transcription factor frequently overexpressed in cancer that upregulates genes involved in glutamine uptake and metabolism, including GLS.
SLC1A5 (ASCT2): A glutamine transporter that is often upregulated in cancer to facilitate increased glutamine uptake.

In many cancers there is an upregulation of key glutaminolysis components:GLS, SLC1A5, c-Myc. Many studies have found that overexpression of glutaminolysis-related enzymes (especially GLS) correlates with aggressive tumor behavior and poor patient outcomes.
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↓, In recent years, a small molecule alkylating agent, 3-bromopyruvate (3-BrPA), being an effective glycolytic inhibitor, has shown great potential as a promising antitumor drug.
mt-OXPHOS↓, Not only it targets glycolysis process, but also inhibits mitochondrial OXPHOS in tumor cells.
HK2↓, The direct inhibition of mitochondrial HK-II isolated from the rabbit liver implanted VX2 tumor via 3-BrPA was demonstrated by Ko et al. [17].
Cyt‑c↑, -BrPA treatment resulted in an increase of cytochrome c release [59,60], along with an elevated expression of active proapoptotic caspase-3 and a decrease of antiapoptotic Bcl-2 and Mcl-1 [59]
Casp3↓,
Bcl-2↓,
Mcl-1↓,
GAPDH↓, Additionally, GAPDH was found to be inhibited by 3-BrPA in several studies
LDH↓, Recent reports showed 3-BrPA had ability to inhibit post glycolysis targets and other metabolic pathways, such as LDH, PDH, TCA cycle, and glutaminolysis
PDH↓, 3-BrPA was proven to be an inhibitor of PDH [72,73,74],
TCA↓,
GlutaM↓, this inhibition of TCA cycle can lead to the impairment of glutaminolysis due to α-KG generated from glutamine is incorporated into the TCA cycle by IDH and αKD activities
GSH↓, Indeed, a remarkable decrease of reduced glutathione (GSH) level was observed after 3-BrPA treatment in both microorganisms and various tumor cells [53,61,65].
ATP↓, 3-BrPA successfully killed AS-30D hepatocellular carcinoma (HCC) cells via the inhibition of both ATP-producing glycolysis and mitochondrial respiration [17].
mitResp↓,
ROS↑, the increase of ROS and concomitant decrease of GSH were commonly found in 3-BrPA-mediated antitumor studies [53,59,61,64,65,76,77,86,89].
ChemoSen↑, When 3-BrPA was combined with cisplatin or oxaliplatin with non-toxic low-dose, 3-BrPA strikingly enhanced the antiproliferative effects of both platinum drugs in HCT116 cells and resistant p53-deficient HCT116 cells [89].
toxicity↝, Finally, two years after the first diagnosis, the patient died due to an overload of liver function rather than the tumor itself [118].

2542- M-Blu,    In Vitro Methylene Blue and Carboplatin Combination Triggers Ovarian Cancer Cells Death
- in-vitro, Ovarian, OV1369 - in-vitro, Ovarian, OV1946 - in-vitro, Nor, ARPE-19
BioAv↝, our study reveals MB’s distinct cellular uptake, with ARPE-19 absorbing 5 to 7 times more MB than OV1946 and OV1369-R2.
TumCP↓, Treatment with 50 µM MB (MB-50) effectively curtailed the proliferation of both ovarian cancer cell lines.
GlutaM↓, MB-50 exhibited the ability to quell glutaminolysis and the Warburg effect in cancer cell cultures.
Warburg↓,
OCR↑, MB-50 spurred oxygen consumption, disrupted glycolytic pathways, and induced ATP depletion in the chemo-sensitive OV1946 cell line.
Glycolysis↓,
ATP↓,
BioAv↝, The reduced permeability of cancer cell membranes, including mitochondria, suggests limited internalization of MB into their cytoplasm or mitochondria, consistent with their preference for aerobic glycolysis, a hallmark of the Warburg effect.
ROS↑, Consistent with our findings, they reported a decrease in intracellular ATP levels, which, in turn, led to increased generation of reactive oxygen species (ROS)


Showing Research Papers: 1 to 2 of 2

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

GSH↓, 1,   mt-OXPHOS↓, 1,   ROS↑, 2,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 2,   mitResp↓, 1,   OCR↑, 1,  

Core Metabolism/Glycolysis ⓘ

GAPDH↓, 1,   GlutaM↓, 2,   Glycolysis↓, 2,   HK2↓, 1,   LDH↓, 1,   PDH↓, 1,   TCA↓, 1,   Warburg↓, 1,  

Cell Death ⓘ

Bcl-2↓, 1,   Casp3↓, 1,   Cyt‑c↑, 1,   Mcl-1↓, 1,  

Migration ⓘ

TumCP↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↝, 2,   ChemoSen↑, 1,  

Clinical Biomarkers ⓘ

LDH↓, 1,  

Functional Outcomes ⓘ

toxicity↝, 1,  
Total Targets: 23

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: GlutaM, Glutaminolysis
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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