Hif1a Cancer Research Results

Hif1a, HIF1α/HIF1a: Click to Expand ⟱
Source:
Type:
Hypoxia-Inducible-Factor 1A (HIF1A gene, HIF1α, HIF-1α protein product)
-Dominantly expressed under hypoxia(low oxygen levels) in solid tumor cells
-HIF1A induces the expression of vascular endothelial growth factor (VEGF)
-High HIF-1α expression is associated with Poor prognosis
-Low HIF-1α expression is associated with Better prognosis

-Functionally, HIF-1α is reported to regulate glycolysis, whilst HIF-2α regulates genes associated with lipoprotein metabolism.
-Cancer cells produce HIF in response to hypoxia in order to generate more VEGF that promote angiogenesis

Key mediators of aerobic glycolysis regulated by HIF-1α.
-GLUT-1 → regulation of the flux of glucose into cells.
-HK2 → catalysis of the first step of glucose metabolism.
-PKM2 → regulation of rate-limiting step of glycolysis.
-Phosphorylation of PDH complex by PDK → blockage of OXPHOS and promotion of aerobic glycolysis.
-LDH (LDHA): Rapid ATP production, conversion of pyruvate to lactate;

HIF-1α Inhibitors:
-Curcumin: disruption of signaling pathways that stabilize HIF-1α (ie downregulate).
-Resveratrol: downregulate HIF-1α protein accumulation under hypoxic conditions.
-EGCG: modulation of upstream signaling pathways, leading to decreased HIF-1α activity.
-Emodin: reduce HIF-1α expression. (under hypoxia).
-Apigenin: inhibit HIF-1α accumulation.
Scientific Papers found: Click to Expand⟱
2974- CUR,    Curcumin Suppresses Metastasis via Sp-1, FAK Inhibition, and E-Cadherin Upregulation in Colorectal Cancer
- in-vitro, CRC, HCT116 - in-vitro, CRC, HT29 - in-vitro, CRC, HCT15 - in-vitro, CRC, COLO205 - in-vitro, CRC, SW-620 - in-vivo, NA, NA
TumCMig↓, Curcumin significantly inhibits cell migration, invasion, and colony formation in vitro and reduces tumor growth and liver metastasis in vivo.
TumCI↓,
TumCG↓,
TumMeta↓,
Sp1/3/4↓, curcumin suppresses Sp-1 transcriptional activity and Sp-1 regulated genes including ADEM10, calmodulin, EPHB2, HDAC4, and SEPP1 in CRC cells.
HDAC4↓,
FAK↓, Curcumin inhibits focal adhesion kinase (FAK) phosphorylation
CD24↓, Curcumin reduces CD24 expression in a dose-dependent manner in CRC cells
E-cadherin↑, E-cadherin expression is upregulated by curcumin and serves as an inhibitor of EMT.
EMT↓,
TumCP↓,
NF-kB↓, CUR prevents cancer cells migration, invasion, and metastasis through inhibition of PKC, FAK, NF-κB, p65, RhoA, MMP-2, and MMP-7 gene expressions
AP-1↝,
STAT3↓, downregulation of CD24 reduces STAT and FAK activity, decreases cell proliferation, metastasis in human tumor
P53?,
β-catenin/ZEB1↓, CUR could activate protein kinase D1 (PKD1) suggesting that suppressing of β-catenin transcriptional activity prevents growth of prostate cancer
NOTCH1↝,
Hif1a↝,
PPARα↝,
Rho↓, CUR prevents cancer cells migration, invasion, and metastasis through inhibition of PKC, FAK, NF-κB, p65, RhoA, MMP-2, and MMP-7 gene expressions
MMP2↓,
MMP9↓,

1880- DCA,    A Novel Form of Dichloroacetate Therapy for Patients With Advanced Cancer: A Report of 3 Cases
- Case Report, Var, NA
OS↑, 3 cases with patients who had recurrent cancers and for whom all conventional therapies had failed
angioG↓, (1) inhibition of angiogenesis
Hif1a↝, (2) alteration of expression of hypoxia-inducible factor 1-α (HIF1-α)
pH↝, (3) alteration of pH regulators vacuolar-type H + -ATPase (V-ATPase) and monocarboxylate transporter 1 (MCT1)
QoL↑, DCA has the potential to extend life without reducing patients’ quality of life with debilitating side effects or compromising physiological function, even for disease in a very advanced stage

4110- MF,    Pulsed Electromagnetic Fields: A Novel Attractive Therapeutic Opportunity for Neuroprotection After Acute Cerebral Ischemia
- Review, Stroke, NA
*ROS↓, PEMFs counteract hypoxia-induced apoptosis and ROS production in neuronal-like cells and exert a strong anti-inflammatory effect on microglial cells.
*Inflam↓, PEMFs exposure is able to reduce the size of the infarct area and decrease the levels of pro-inflammatory mediators.
*other↝, Pulsed electromagnetic fields (PEMFs) act as modulators of adenosine receptors (ARs); in particular, PEMF stimulation induces a significant upregulation of A2A and A3 ARs in different cell types.
*neuroP↑, PEMFs through the specific action on A2A and A3 ARs show great potential to be exploited also to control brain inflammation and to provide neuroprotection following brain damage.
*Apoptosis↓, PEMFs exposure significantly reduced apoptosis, partially restored hypoxia inducible factor-1α (HIF-1α) activation to normoxic conditions, and inhibited ROS production.
*Hif1a↝,

596- VitC,    High-Dose Vitamin C in Advanced-Stage Cancer Patients
- Review, NA, NA
ChemoSideEff↓, reducing cancer-related symptoms, such as fatigue and bone pain
ROS↑, is able to reduce catalytic metals such as Fe3+ to Fe2+ and Cu2+ to Cu+, increasing the pro-oxidant chemistry of these metals and facilitating the generation of reactive oxygen species
H2O2↑, Reactions of ascorbate with oxygen or with free transition metal ions lead to the generation of superoxide, H2O2 and highly reactive oxidants, such as the hydroxyl radical by promoting the Fenton chemistry
Fenton↑,
Hif1a↝, Ascorbate regulates the transcription of hypoxia inducible factor-1α (HIF-1α)
Dose↑, Results obtained from in vitro studies revealed that millimolar ascorbate plasma concentrations, achievable only after intravenous vitamin C administration, are cytotoxic to fast-growing malignant cells.
BioAv↓, For this reason, ascorbate concentration in plasma does not exceed 100 μmol/L when it is supplied orally with food; even with oral supplementation approaching maximum tolerated doses, it is always <250 μmol/L
Dose↝, 100 mg, the concentration of ascorbate in daily fasting plasma reaches a plateau between 50–60 µmol/L [24]. Whereas increasing the daily dose ten times to 1000 mg gives only a slight increase in plasma concentration to 70–85 μmol/L
Half-Life↝, high concentrations are relatively transient due to the rapid clearance by the kidneys resulting in a half-life of about 2 h in circulation
IL1β↓, IVC (15–50 g up to three times a week) resulted in reduced CRP levels (in 76 ± 13% of study participants) and reduced concentration of pro-inflammatory cytokines (IL-1α, IL-1β, IL-2, IL-8, tumor necrosis factor TNF-α)
IL2↓,
IL8↓,
TNF-α↓,

2281- VitK2,    The biological responses of vitamin K2: A comprehensive review
- Review, Var, NA
*ROS↓, VitK1 and MK-4 prevent oxidative cell death by blocking the activation of 12-LOX and ROS generation
*12LOX↓,
*NF-kB↓, VitK2 modulates osteoblast and osteoclast formation and activity via downregulation of basal and cytokine-induced NF-κB activation
*BMD↑, strengthens bone construction
*hepatoP↑, VitK2 significantly increased serum albumin levels with concurrent reduction of the levels of alanine and aspartate aminotransferases, suggesting that VitK2 enhances liver regeneration.
cycD1/CCND1↓, figure 5
PKCδ↓,
STAT3↓,
ERK↑,
MAPK↓,
ROS↑,
PI3K↝,
Akt↝,
Hif1a↝,
*neuroP↑, An increasing body of evidence suggests the possible role of VitK supplementation as a novel neuroprotective strategy in the maintenance of nerve integrity and normal brain function, including cognition and behavior


Showing Research Papers: 1 to 5 of 5

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 5

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Fenton↑, 1,   H2O2↑, 1,   ROS↑, 2,  

Core Metabolism/Glycolysis ⓘ

PPARα↝, 1,  

Cell Death ⓘ

Akt↝, 1,   MAPK↓, 1,  

Kinase & Signal Transduction ⓘ

Sp1/3/4↓, 1,  

DNA Damage & Repair ⓘ

P53?, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

CD24↓, 1,   EMT↓, 1,   ERK↑, 1,   HDAC4↓, 1,   NOTCH1↝, 1,   PI3K↝, 1,   STAT3↓, 2,   TumCG↓, 1,  

Migration ⓘ

AP-1↝, 1,   E-cadherin↑, 1,   FAK↓, 1,   MMP2↓, 1,   MMP9↓, 1,   PKCδ↓, 1,   Rho↓, 1,   TumCI↓, 1,   TumCMig↓, 1,   TumCP↓, 1,   TumMeta↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   Hif1a↝, 4,  

Immune & Inflammatory Signaling ⓘ

IL1β↓, 1,   IL2↓, 1,   IL8↓, 1,   NF-kB↓, 1,   TNF-α↓, 1,  

Cellular Microenvironment ⓘ

pH↝, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   Dose↑, 1,   Dose↝, 1,   Half-Life↝, 1,  

Functional Outcomes ⓘ

ChemoSideEff↓, 1,   OS↑, 1,   QoL↑, 1,  
Total Targets: 44

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

ROS↓, 2,  

Core Metabolism/Glycolysis ⓘ

12LOX↓, 1,  

Cell Death ⓘ

Apoptosis↓, 1,  

Transcription & Epigenetics ⓘ

other↝, 1,  

Angiogenesis & Vasculature ⓘ

Hif1a↝, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,   NF-kB↓, 1,  

Clinical Biomarkers ⓘ

BMD↑, 1,  

Functional Outcomes ⓘ

hepatoP↑, 1,   neuroP↑, 2,  
Total Targets: 10

Scientific Paper Hit Count for: Hif1a, HIF1α/HIF1a
1 Curcumin
1 Dichloroacetate
1 Magnetic Fields
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#:143  State#:%  Dir#:4
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