CA Cancer Research Results

CA, Carbonic anhydrases: Click to Expand ⟱
Source:
Type:
CA pH Control, Hypoxia Adaptation, and Metastatic Fitness Family of enzymes that catalyze the reversible hydration of carbon dioxide (CO₂) to bicarbonate (HCO₃⁻) and a proton (H⁺).
Carbonic Anhydrase IX (CAIX) is a well-described enzyme in renal cell carcinoma, with its expression being regulated by the hypoxia-inducible factor 1 alpha, it is known for interfering with hypoxia processes.
Carbonic anhydrase 9 (CA9) is a protein to be upregulated under exposure to hypoxic conditions. Hypoxic conditions are known to be associated with resistance to chemotherapy and radiotherapy, and with poor cancer prognosis.
Of the carbonic anhydrases, CA9 and CA12, are transmembrane isozymes that are highly expressed in some tumours, and may be implicated in acidification of the extracellular milieu surrounding cancer cells, thus creating a microenvironment conducive to tumour growth and spread.
Carbonic anhydrase IX, is an endogenous marker for hypoxia.
Scientific Papers found: Click to Expand⟱
5314- acetaz,    Carbonic Anhydrase Inhibitors Targeting Metabolism and Tumor Microenvironment
- Review, Var, NA
AntiTum↑, such as CA IX and XII, actively participate in these processes and were validated as antitumor/antimetastatic drug targets.
CA↓, Indeed, primary sulfonamides [56,57,58] such as acetazolamide were known for decades to potently inhibit CAs

5964- CEL,    Celecoxib pathways: pharmacokinetics and pharmacodynamics
- Review, Var, NA
COX2↓, purposefully designed as COX-2-selective inhibitors
*Pain↓, one of the most frequently prescribed drugs for the relief of pain and inflammation
*Inflam↓,
Apoptosis↑, proposed anticarcinogenic mechanisms of celecoxib include induction of apoptosis, cell cycle arrest, regulation of angiogenesis, and induction of endoplasmic reticulum (ER) stress.
TumCCA↑,
angioG↓,
ER Stress↑,
VEGF↓, Celecoxib treatment decreased the expression of vascular endothelial cell growth factor [53-55] and inhibition of matrix metalloproteinase 9
MMP9↓,
PDK1↓, inhibition of PDK1/Akt signaling correlated with celecoxib-induced apoptosis in both colon and prostate tumor cell lines [
Akt↓,
CA↓, Carbonic anhydrases (CA), enzymes that catalyze the reversible hydration of carbon dioxide, are also inhibited by celecoxib (IC50 in the low nanomolar range)
CardioT↑, selective COX-2 inhibitors, rofecoxib, valdecoxib, and celecoxib with an increased incidence of myocardial infarction, stroke, and death due to cardiovascular causes

5962- CEL,    The cyclooxygenase-2 inhibitor celecoxib is a potent inhibitor of human carbonic anhydrase II
- Study, Var, NA
CA↓, COX-2 inhibitors (i.e., celecoxib, valdecoxib, and rofecoxib); among these effects are carbonic anhydrase (CA) inhibition.

5961- CEL,    Dual Cyclooxygenase and Carbonic Anhydrase Inhibition by Nonsteroidal Anti-Inflammatory Drugs for the Treatment of Cancer
- Review, Var, NA
COX2↓, dual inhibition of CA and COX enzymes, supporting the evidence that inflammation and hypoxia pathways are involved in cancer onset and progression
CA↓,

5958- CEL,    Unexpected nanomolar inhibition of carbonic anhydrase by COX-2-selective celecoxib: new pharmacological opportunities due to related binding site recognition
- in-vitro, Var, NA
COX2↓, selective inhibition of inducible cyclooxygenase COX-2
CA↓, carbonic anhydrase (CA) inhibitors.

5956- CEL,    Direct non-cyclooxygenase-2 targets of celecoxib and their potential relevance for cancer therapy
- Review, Var, NA
COX2↓, Celecoxib (Celebrex®) was developed as a selective cyclooxygenase-2 (COX-2) inhibitor for the treatment of chronic pain.
Pain↓,
CA↓, celecoxib displayed potent CA inhibitory activity in the low nanomolar range in vitro
PDK1↓, Much excitement was generated by the finding that celecoxib could bind to and inhibit PDK1
Apoptosis↑, Celecoxib is unique among the coxibs and traditional NSAIDs, because this particular drug displays the greatest potency to induce apoptotic cell death.

972- MAG,    Magnolol suppresses hypoxia-induced angiogenesis via inhibition of HIF-1α/VEGF signaling pathway in human bladder cancer cells
- vitro+vivo, Bladder, T24/HTB-9
angioG↓,
VEGF↓,
H2O2↓,
Hif1a↓,
VEGFR2↓,
Akt↓,
mTOR↓,
P70S6K↓,
4E-BP1↓,
TumCG↓,
CD31↓,
CA↓, carbonic anhydrase IX

3282- SIL,    Role of Silymarin in Cancer Treatment: Facts, Hypotheses, and Questions
- Review, NA, NA
hepatoP↑, This group of flavonoids has been extensively studied and they have been used as hepato-protective substances
AntiCan↑, however, silymarin compounds have clear anticancer effects
TumCMig↓, decreasing migration through multiple targeting, decreasing hypoxia inducible factor-1α expression, i
Hif1a↓, In prostate cancer cells silibinin inhibited HIF-1α translation
selectivity↑, antitumoral activity of silymarin compounds is limited to malignant cells while the nonmalignant cells seem not to be affected
toxicity∅, long history of silymarin use in human diseases without toxicity after prolonged administration.
*antiOx↑, as an antioxidant, by scavenging prooxidant free radicals
*Inflam↓, antiinflammatory effects similar to those of indomethacin,
TumCCA↑, MDA-MB 486 breast cancer cells, G1 arrest was found due to increased p21 and decreased CDKs activity
P21↑,
CDK4↓,
NF-kB↓, human prostate carcinoma cells, silymarin decreased ligand binding to Erb1 135 and NF-kB expression was strongly inhibited by silymarin in hepatoma cell
ERK↓, human prostate carcinoma cells, silymarin decreased ligand binding to Erb1 135 and NF-kB expression was strongly inhibited by silymarin in hepatoma cell
PSA↓, Treating prostate carcinoma cells with silymarin the levels of PSA were significantly decreased and cell growth was inhibited through decreased CDK activity and induction of Cip1/p21 and Kip1/p27. 1
TumCG↓,
p27↑,
COX2↓, such as anti-COX2 and anti-IL-1α activity, 140 antiangiogenic effects through inhibition of VEGF secretion, upregulation of Insulin like Growth Factor Binding Protein 3 (IGFBP3), 141 and inhibition of androgen receptors.
IL1↓,
VEGF↓,
IGFBP3↑,
AR↓,
STAT3↓, downregulation of the STAT3 pathway which was seen in many cell models.
Telomerase↓, silymarin has the ability to decrease telomerase activity in prostate cancer cells
Cyt‑c↑, mitochondrial cytochrome C release-caspase activation.
Casp↑,
eff↝, Malignant p53 negative cells show only minimal apoptosis when treated with silymarin. Therefore, one conclusion is that silymarin may be useful in tumors with conserved p53.
HDAC↓, inhibit histone deacetylase activity;
HATs↑, increase histone acetyltransferase activity
Zeb1↓, reduce expression of the transcription factor ZEB1
E-cadherin↑, increase expression of E-cadherin;
miR-203↑, increase expression of miR-203
NHE1↓, reduce activation of sodium hydrogen isoform 1 exchanger (NHE1)
MMP2↓, target β catenin and reduce the levels of MMP2 and MMP9
MMP9↓,
PGE2↓, reduce activation of prostaglandin E2
Vim↓, suppress vimentin expression
Wnt↓, inhibit Wnt signaling
angioG↓, Silymarin inhibits angiogenesis.
VEGF↓, VEGF downregulation
*TIMP1↓, Silymarin has the capacity to decrease TIMP1 expression166–168 in mice.
EMT↓, found that silibinin had no effect on EMT. However, the opposite was found in other malignant tissues160–162 where it showed inhibitory effects.
TGF-β↓, Silibinin reduces the expression of TGF β2 in different tumors such as triple negative breast, 174 prostate, and colorectal cancers.
CD44↓, Silibinin decreased CD44 expression and the activation of EGFR (epidermal growth factor receptor)
EGFR↓,
PDGF↓, silibinin had the ability to downregulate PDFG in fibroblasts, thus decreasing proliferation.
*IL8↓, Flavonoids, in general, reduce levels of IL-8. Curcumin, 200 apigenin, 201 and silybin showed the ability to decrease IL-8 levels
SREBP1↓, Silymarin inhibited STAT3 phosphorylation and decreased the expression of intranuclear sterol regulatory element binding protein 1 (SREBP1), decreasing lipid synthesis.
MMP↓, reduced membrane potential and ATP content
ATP↓,
uPA↓, silibinin decreased MMP2, MMP9, and urokinase plasminogen activator receptor level (uPAR) in neuroblastoma cells. uPAR is also a marker of cell invasion.
PD-L1↓, Silibinin inhibits PD-L1 by impeding STAT5 binding in NSCLC.
NOTCH↓, Silybin inhibited Notch signaling in hepatocellular carcinoma cells showing antitumoral effects
*SIRT1↑, Silymarin can also increase SIRT1 expression in other tissues, such as hippocampus, 221 articular chondrocytes, 222 and heart muscle
SIRT1↓, Silymarin seems to act differently in tumors: in lung cancer cells SIRT downregulated SIRT1 and exerted multiple antitumor effects such as reduced adhesion and migration and increased apoptosis.
CA↓, Silymarin has the ability to inhibit CA isoforms CA I and CA II.
Ca+2↑, ilymarin increases mitochondrial release of Ca++ and lowers mitochondrial membrane potential in cancer cell
chemoP↑, Silymarin: Decreasing Side Effects and Toxicity of Chemotherapeutic Drugs
cardioP↑, There is also evidence that it protects the heart from doxorubicin toxicity, however, it is less potent than quercetin in this effect.
Dose↝, oral administration of 240 mg of silybin to 6 healthy volunteers the following results were obtained 377 : maximum\,plasmaconcentration0.34±0.16⁢𝜇⁢g/m⁢L
Half-Life↝, and time to maximum plasma concentration 1.32 ± 0.45 h. Absorption half life 0.17 ± 0.09 h, elimination half life 6.32 ± 3.94 h
BioAv↓, silymarin is not soluble in water and oral administration shows poor absorption in the alimentary tract (approximately 1% in rats,
BioAv↓, Our conclusion is that, from a bioavailability standpoint, it is much easier to achieve migration inhibition, than proliferative reduction.
BioAv↓, Combination with succinate: is available on the market under the trade mark Legalon® (bis hemisuccinate silybin). Combination with phosphatidylcholine:
toxicity↝, 13 g daily per os divided into 3 doses was well tolerated. The most frequent adverse event was asymptomatic liver toxicity.
Half-Life↓, It may be necessary to administer 800 mg 4 times a day because the half-life is short.
ROS↓, its ability as an antioxidant reduces ROS production
FAK↓, Silibinin decreased human osteosarcoma cell invasion through Erk inhibition of a FAK/ERK/uPA/MMP2 pathway


Showing Research Papers: 1 to 8 of 8

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 8

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

H2O2↓, 1,   ROS↓, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 1,   MMP↓, 1,  

Core Metabolism/Glycolysis ⓘ

PDK1↓, 2,   SIRT1↓, 1,   SREBP1↓, 1,  

Cell Death ⓘ

Akt↓, 2,   Apoptosis↑, 2,   Casp↑, 1,   Cyt‑c↑, 1,   p27↑, 1,   Telomerase↓, 1,  

Transcription & Epigenetics ⓘ

HATs↑, 1,  

Protein Folding & ER Stress ⓘ

ER Stress↑, 1,  

Cell Cycle & Senescence ⓘ

CDK4↓, 1,   P21↑, 1,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

4E-BP1↓, 1,   CD44↓, 1,   EMT↓, 1,   ERK↓, 1,   HDAC↓, 1,   IGFBP3↑, 1,   mTOR↓, 1,   NOTCH↓, 1,   P70S6K↓, 1,   STAT3↓, 1,   TumCG↓, 2,   Wnt↓, 1,  

Migration ⓘ

CA↓, 8,   Ca+2↑, 1,   CD31↓, 1,   E-cadherin↑, 1,   FAK↓, 1,   miR-203↑, 1,   MMP2↓, 1,   MMP9↓, 2,   PDGF↓, 1,   TGF-β↓, 1,   TumCMig↓, 1,   uPA↓, 1,   Vim↓, 1,   Zeb1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 3,   EGFR↓, 1,   Hif1a↓, 2,   VEGF↓, 4,   VEGFR2↓, 1,  

Barriers & Transport ⓘ

NHE1↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 5,   IL1↓, 1,   NF-kB↓, 1,   PD-L1↓, 1,   PGE2↓, 1,   PSA↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 3,   Dose↝, 1,   eff↝, 1,   Half-Life↓, 1,   Half-Life↝, 1,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

AR↓, 1,   EGFR↓, 1,   PD-L1↓, 1,   PSA↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   AntiTum↑, 1,   cardioP↑, 1,   CardioT↑, 1,   chemoP↑, 1,   hepatoP↑, 1,   Pain↓, 1,   toxicity↝, 1,   toxicity∅, 1,  
Total Targets: 76

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,  

Core Metabolism/Glycolysis ⓘ

SIRT1↑, 1,  

Migration ⓘ

TIMP1↓, 1,  

Immune & Inflammatory Signaling ⓘ

IL8↓, 1,   Inflam↓, 2,  

Functional Outcomes ⓘ

Pain↓, 1,  
Total Targets: 6

Scientific Paper Hit Count for: CA, Carbonic anhydrases
5 Celecoxib
1 acetazolamide
1 Magnolol
1 Silymarin (Milk Thistle) silibinin
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#:37  State#:%  Dir#:1
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