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⟱

306-

AgNPs,

Cancer Therapy by Silver Nanoparticles: Fiction or Reality?

Analysis,

NA,

EPR↝, takes advantage of EPR
ROS↑, silver ions drive the formation of ROS, which triggers massive oxidative stress, thereby activating the cellular pathways leading to cell death
IL1↑, IL-1b
IL8↑, IL-8 mRNA levels
ER Stress↑,
MMP9↑, it has been shown that 20 nm AgNPs increase the MMP-9 secretion
MMP↓, loss of mitochondrial membrane potential and mitochondrial structural disorganization, were reported to accompany the AgNP-induced stres
Cyt‑c↑, cytochrome c release from the mitochondria into the cytoplasm and finally to apoptosis
Apoptosis↑,
Hif1a↑, AgNPs were shown to induce HiF-1α activation, thereby ultimately activating autophagy through the AMPK-mTOR pathway in PC-3 prostate cancer cells [89
BBB↑, AgNPs can affect the integrity of the blood–brain barrier and can cross this barrier in vitro through transcytosis
GutMicro↝, AgNP treatments might influence the composition of the gut microbiota,
eff↑, AgNPs are promising tools for targeted delivery
eff↑, the joint application of the nanoparticles and the HDAC inhibitor caused significantly increased ROS levels,
RadioS↑, idea to use AgNPs as radiosensitizers came along with the phenomenon that metals with high atomic numbers are capable of enhancing the effects of radiation

357-

AgNPs,

Hypoxia-mediated autophagic flux inhibits silver nanoparticle-triggered apoptosis in human lung cancer cells

in-vitro,

Lung,

A549

in-vitro,

Lung,

L132

mtDam↑,
ROS↑,
Hif1a↑, HIF-1α expression was upregulated after AgNPs treatment under both hypoxic and normoxic conditions HIF-1α knockdown enhances hypoxia induced decrease in cell viability
LC3s↑,
p62↑,
eff↓, Hypoxia decreases the effects of anticancer drugs in solid tumor cells through the regulation of HIF-1α

232-

AL,

A Single Meal Containing Raw, Crushed Garlic Influences Expression of Immunity- and Cancer-Related Genes in Whole Blood of Humans

Human,

Nor,

17 volunteers consumed a garlic-containing meal (100 g white bread, 15 g butter, and 5 g raw, crushed garlic)

*AhR↑, x2.6 increase
*ARNT↑, x1.8 increase
*Hif1a↑, x1.6 increase (whole blood)
*Jun↑, x1.7 increase, x12@3-6hrs
*NFAT↑,
*NFAM1↑, 3 fold increase
*REL↑, x1.7 increase
*OSM↑, x1.8 increase
*NFAT↑, x1.4 increase NFATC3
*CXCc↑, x1.3 increase CXCL14
*IL2↑, x1.1
*IL6↑, x1.3
*LIF↑, x1.4

3271-

ALA,

Decrypting the potential role of α-lipoic acid in Alzheimer's disease

Review,

AD,

*antiOx↑, Alpha-lipoic acid (α-LA), a natural antioxidant
*memory↑, multiple preclinical studies indicating beneficial effects of α-LA in memory functioning, and pointing to its neuroprotective effects
*neuroP↑, α-LA could be considered neuroprotective
*Inflam↓, α-LA shows antioxidant, antiapoptotic, anti-inflammatory, glioprotective, metal chelating properties in both in vivo and in vitro studies.
*IronCh↑, α-LA leads to a marked downregulation in iron absorption and active iron reserve inside the neuron
*NRF2↑, α-LA induces the activity of the nuclear factor erythroid-2-related factor (Nrf2), a transcription factor.
*BBB↑, capable of penetrating the BBB
*GlucoseCon↑, Fig 2, α-LA mediated regulation of glucose uptake
*Ach↑, α-LA may show its action on the activity of the ChAT enzyme, which is an essential enzyme in acetylcholine metabolism
*ROS↓,
*p‑tau↓, decreased degree of tau phosphorylation following treatment with α-LA
*Aβ↓, α-LA possibly induce the solubilization of Aß plaques in the frontal cortex
*cognitive↑, cognitive reservation of α-LA served AD model was markedly upgraded in additional review
*Hif1a↑, α-LA treatment efficaciously induces the translocation and activity of hypoxia-inducible factor-1α (HIF-1α),
*Ca+2↓, research found that α-LA therapy remarkably declines Ca2+ concentration and calpain signaling
*GLUT3↑, inducing the downstream target genes expression, such as GLUT3, GLUT4, HO-1, and VEGF.
*GLUT4↑,
*HO-1↑,
*VEGF↑,
*PDKs↓, α-LA also ameliorates survival in mutant mice of Huntington's disease [150–151], possibly due to the inhibition of the activity of pyruvate dehydrogenase kinase
*PDH↑, α-LA administration enhances PDH expression in mitochondrial hepatocytes by inhibiting the pyruvate dehydrogenase kinase (PDK),
*VCAM-1↓, α-LA inhibits the expression of cell-cell adhesion molecule-1 and VCAM-1 in spinal cords and TNF-α induced neuronal endothelial cells injury
*GSH↑, α-LA may enhance glutathione production in old-aged models
*NRF2↑, activation of the Nrf2 signaling by α-LA
*hepatoP↑, α-LA also protected the liver against oxidative stress-mediated hepatotoxicity
*ChAT↑, α-LA in mice models may prevent neuronal injury possibly due to an increase in ChAT in the hippocampus of animal models

3433-

ALA,

Alpha lipoic acid promotes development of hematopoietic progenitors derived from human embryonic stem cells by antagonizing ROS signals

*ROS↓, However, in more mature hPSC‐derived hematopoietic stem/progenitor cells, ALA reduced ROS levels and inhibited apoptosis.
*Apoptosis↓,
*Hif1a↑, up‐regulating HIF1A in response to a hypoxic environment.
*FOXO1↑, ALA also up‐regulated sensor genes of ROS signals, including HIF1A, FOXO1, FOXO3, ATM, PETEN, SIRT1, and SIRT3, during the process of hPSCs derived hemogenic endothelial cells generation
*FOXO3↑,
*ATM↑,
*SIRT1↑,
*SIRT3↑,
*CD34↑, Flow cytometry analysis indicated that ALA improved the production of CD34+ CD43+ CD45+ hematopoietic stem/progenitor cells significantly

3441-

ALA,

α-Lipoic Acid Maintains Brain Glucose Metabolism via BDNF/TrkB/HIF-1α Signaling Pathway in P301S Mice

in-vivo,

AD,

mice

*tau↓, α-lipoic acid (LA), which is a naturally occurring cofactor in mitochondrial, has been shown to have properties that can inhibit the tau pathology and neuronal damage in our previous research
*GlucoseCon↑, chronic LA administration significantly increased glucose availability by elevating glucose transporter 3 (GLUT3), GLUT4, vascular endothelial growth factor (VEGF) protein and mRNA level, and heme oxygenase-1 (HO-1) protein level in P301S mouse brain
*GLUT3↑,
*GLUT4↑,
*VEGF↑,
*HO-1↑,
*Glycolysis↑, LA also promoted glycolysis by directly upregulating hexokinase (HK) activity, indirectly by increasing proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and DNA repair enzymes (OGG1/2 and MTH1).
*HK1↑, Our results indicated that the activity of HK was significantly increased after 10 mg/kg LA treatment.
*PGC-1α↑,
*Hif1a↑, found the underlying mechanism of restored glucose metabolism might involve in the activation of brain-derived neurotrophic factor (BDNF)/tyrosine Kinase receptor B (TrkB)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway by LA treatment.
*neuroP↑,

3442-

ALA,

α‑lipoic acid modulates prostate cancer cell growth and bone cell differentiation

in-vitro,

Pca,

22Rv1

in-vitro,

Pca,

C4-2B

in-vitro,

Nor,

3T3

tumCV↓, Notably, α‑LA treatment significantly reduced the cell viability, migration, and invasion of PCa cell lines in a dose‑dependent manner.
TumCMig↓,
TumCI↓,
ROS↑, α‑LA supplementation dramatically increased reactive oxygen species (ROS) levels and HIF‑1α expression, which started the downstream molecular cascade and activated JNK/caspase‑3 signaling pathway
Hif1a↑, The expression of HIF-1α significantly increased following α-LA treatment and was comparable with the changes in ROS.
JNK↑,
Casp↑,
TumCCA↑, arrest of the cell cycle in the S‑phase, which has led to apoptosis of PCa cells
Apoptosis↑,
selectivity↑, Also, the treatment of α‑LA improved bone health by reducing PCa‑mediated bone cell modulation.

277-

ALA,

α-lipoic acid modulates prostate cancer cell growth and bone cell differentiation

in-vitro,

Pca,

22Rv1

 500 μM

in-vitro,

Pca,

C4-2B

ROS↑, α-LA supplementation dramatically increased reactive oxygen species (ROS) levels and HIF-1α expression, which started the downstream molecular cascade and activated JNK/caspase-3 signaling pathway.
Hif1a↑, HIF-1α, is a key regulator in response to cellular stressors, and excessive ROS levels can influence its expression. (HIF-1α) is essential for the physiological response to hypoxia(resulting from elevated intracellular ROS levels)
JNK↑,
Casp3↑,
P21↑,
BAX↑,
Bcl-xL↓,
cFos↓,

2653-

Cela,

Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical Evidence

Review,

Var,

chemoPv↑, It has been widely studied as chemopreventive and anticancer drug
Catalase↑,
ROS↑, ROS induction has been attributed as the primary mode through which celastrol mediates its anticancer effects.
HSP90↓, celastrol has been reported to inhibit HSP90 function
Sp1/3/4↓, induce suppressor of specificity protein (Sp) repressors [79], activate the PKCzeta–AMPK-p53–PLK 2 signaling axis [73], and activate the JNK pathway [80,81] to induce apoptosis.
AMPK↑,
P53↑,
JNK↑,
ER Stress↑, celastrol induces ER stress [78], mitochondrial dysfunction, specifically disruption of mitochondrial membrane potential [72,78,82], and cell cycle arrest at G2/M phase [76,77] and S phase [75]
MMP↓,
TumCCA↑,
TumAuto↑, Interestingly, at low concentrations (i.e., below the cytotoxic threshold) celastrol was found to induce autophagy in gastric cancer cells through ROS-mediated accumulation of hypoxia-inducible factor 1-α via the transient activation of AKT.
Hif1a↑,
Akt↑,
other↓, (1) inhibition of mitochondrial respiratory chain complex I activity [80];
Prx↓, (2) inhibition of peroxiredoxins, namely peroxiredoxin-1 [76] and peroxiredoxin-2 [78].

5519-

EP,

Nanosecond Pulsed Electric Fields (nsPEFs) for Precision Intracellular Oncotherapy: Recent Advances and Emerging Directions

Review,

Var,

MMP↓, nsPEF bypasses plasma-membrane shielding to porate organelles, collapse mitochondrial potential, perturb ER calcium, and transiently open the nuclear envelope.
Ca+2↑,
eff↑, synergy with checkpoint blockade.
ER Stress↑, capacity to directly target organelles such as mitochondria, endoplasmic reticulum (ER),
selectivity↑, selectively ablate solid tumors, suppress metastatic spread, and prime systemic anti-tumor immunity while sparing adjacent normal tissue [7,9,10,11,12,13,14,15].
CSCs↓, Preclinical investigations have demonstrated that nsPEFs significantly reduce CSC-associated subpopulations, including CD44+/CD24− cells in breast cancer xenografts and CD133+ glioma stem-like cells
CD44↓,
CD133↓,
ROS↑, nsPEFs release Ca2+ from the ER, disrupt mitochondrial membrane potential, induce reactive oxygen species (ROS) generation, and perturb nuclear chromatin structure within nanoseconds
Imm↑, nsPEFs not only eliminate local tumor cells but also convert the tumor into an in situ vaccine, amplifying their therapeutic relevance in the era of immunotherapy
DNAdam↑, figure 2
MOMP↑, induce mitochondrial outer membrane permeabilization (MOMP)
Cyt‑c↑,
Casp9↑, Subsequent release of cytochrome c enables apoptosome assembly, caspase-9 activation, and downstream activation of caspases-3/7, culminating in cell death
Casp3↑,
Casp9↑,
TumCD↑,
Fas↑, In certain cell types, nsEP can also activate the extrinsic pathway, where Fas receptor clustering stimulates caspase-8.
UPR↑, This rapid surge triggers ER stress pathways, activates unfolded protein response (UPR) signaling, and promotes cross-talk with mitochondria through mitochondria-associated membranes (MAMs)
Dose↝, longer ns pulses (100–300 ns) generate sustained plasma membrane charging, resulting in robust Ca2+ influx, osmotic imbalance, and apoptotic priming.
Dose↝, A critical threshold of 10–20 kV/cm is generally required to initiate pore formation in malignant cells, with higher amplitudes (>30–40 kV/cm) producing more extensive permeabilization [100].
Dose↓, Low pulse counts (<100) frequently produce reversible stress responses, such as transient mitochondrial depolarization or ER Ca2+ release, without committing cells to apoptosis. I
Dose↑, In contrast, higher pulse counts (500–1000) lead to irreversible apoptosis, caspase activation, and release of DAMPs that initiate ICD [80,106].
HMGB1↓, ICD after nsPEF is characterized by surface exposure of calreticulin, extracellular ATP release, and HMGB1 emission
eff↑, The integration of nsPEFs with NP-based systems thus represents a synergistic platform where physical membrane poration and molecular targeting cooperate to maximize therapeutic efficacy.
EPR↑, demonstrates that PEF + AuNPs enhanced membrane permeabilization compared with PEF alone,
ChemoSen↑, The superior efficacy of delayed drug administration following nsPEF exposure can be attributed to transient biophysical and biochemical changes that persist after pulsing.
ETC↝, study demonstrated that nsPEFs dynamically alter trans-plasma membrane electron transport (tPMET) and mitochondrial electron transport chain activity, resulting in differential ROS generation in cancer versus non-cancer cells (Figure 9).
*AntiAge↑, Mechanistically, nsPEFs upregulated HIF-1α and SIRT1, mediators of mitochondrial retrograde signaling, thereby reversing hallmarks of aging
*Hif1a↑,
*SIRT1↑,

5523-

EP,

Nanosecond pulsed electric field applications rejuvenate aging endothelial cells by rescuing mitochondrial-to-nuclear retrograde communication

vitro+vivo,

Nor,

HUVECs

Forty male C57BL/6 mice

*MMP↑, NsPEF treatment reverses d-galactose-induced endothelial senescence by restoring mitochondrial membrane potential. marked elevation in mitochondrial membrane potential
*Hif1a↑, NsPEF activates key MNRC markers HIF-1α and SIRT1, rescuing mitochondrial-nuclear communication.
*SIRT1↑,
*ROS↓, These effects were confirmed by concurrent reductions in SA-β-Gal activity and in ROS production, and increases in EdU-positive (DNA-synthesizing) cells.
*AntiAge↑, These findings suggest that nsPEF treatments rescue ECs from aging by restoring MNRC, highlighting its potential as a therapeutic strategy for age-related vascular diseases.
*Dose↝, mice received daily nsPEF treatment (3 kV/cm) for 14 consecutive days.
*angioG↑, The nsPEF treatments stimulate skin angiogenesis in different aged rodent models.

3716-

FA,

Ferulic Acid as a Protective Antioxidant of Human Intestinal Epithelial Cells

in-vitro,

IBD,

0–500 μM for 24 h

in-vivo,

NA,

*antiOx↑, Ferulic acid (FA) is a polyphenol that is abundant in plants and has antioxidant and anti-inflammatory properties
*Inflam↓,
*ER Stress↓, FA suppressed ER stress, nitric oxide (NO) generation, and inflammation in polarized Caco-2 and T84 cells,
*other↑, FA has a protective effect on intestinal tight junctions
*angioG↑, A has been reported to induce hypoxia and enhance the angiogenesis of human umbilical vein endothelial cells (HUVEC) by increasing the expressions of HIF-1α and vascular endothelial growth factor (VEGF)
*Hif1a↑,
*VEGF↑,
*NO↓, suggesting FA attenuates NO production induced by inflammation.
*SIRT1↑, Another study suggested that FA activated SIRT1 to protect the heart from the adverse effects of ER stress via reduction of PERK/eIF2α/ATF4/CHOP pathway
*PERK↓,
*ATF4↓,
*CHOP↓,
*GutMicro↑, FA can mitigate intestinal inflammation, promote the growth of Bacteroides, and induce the production of SCFAs by modulating the gut microbiota in mouse and diabetic syndrome rat model

3479-

MF,

Evaluation of Pulsed Electromagnetic Field Effects: A Systematic Review and Meta-Analysis on Highlights of Two Decades of Research In Vitro Studies

Review,

NA,

*eff↓, evidence suggests that frequencies higher than 100 Hz, flux densities between 1 and 10 mT, and chronic exposure more than 10 days would be more effective in establishing a cellular response
eff↝, undifferentiated PC12 cells are more sensitive to PEMF exposure, while differentiated PC12 cells are more resistant to stress
*Hif1a↑, Retinal pigment epithelial (RPE) cells Frequency of 50 Hz Intensity of 1 mT : HIF-1α, VEGFA, VEGFR-2, CTGF, cathepsin D TIMP-1, E2F3, MMP-2, and MMP-9) increased
*VEGF↑,
*TIMP1↑,
*E2Fs↑,
*MMP2↑,
*MMP9↑,
Apoptosis↑, MCF7, MCF10 Frequencies of 20 and 50 Hz Intensities of 2.0, 3.0, and 5.0 mT Cell apoptosis

3482-

MF,

Pulsed Electromagnetic Fields Increase Angiogenesis and Improve Cardiac Function After Myocardial Ischemia in Mice

in-vitro,

NA,

mice

*cardioP↑, PEMF treatment with 30 Hz 3.0 mT significantly improved heart function.
*VEGF↑, PEMF treatment with 15 Hz 1.5 mT and 30 Hz 3.0 mT both increased capillary density, decreased infarction area size, increased the protein expression of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR2
*VEGFR2↑,
*Hif1a↑, and increased the mRNA level of VEGF and hypoxia inducible factor 1-alpha (HIF-1α) in the infarct border zone.
*FGF↑, Additionally, treatment with 30 Hz 3.0 mT also increased protein and mRNA level of fibroblast growth factor 2 (FGF2), and protein level of β1 integrin, and shows a stronger therapeutic effect.
*ITGB1↑,
*angioG↑, PEMFs Improve Angiogenesis In Vivo

1812-

Oxy,

Hyperbaric oxygen suppressed tumor progression through the improvement of tumor hypoxia and induction of tumor apoptosis in A549-cell-transferred lung cancer

in-vitro,

Lung,

A549

in-vivo,

Lung,

mouse

in-vitro,

NA,

BEAS-2B

TumCG↓, HBOT not only improved tumor hypoxia but also suppressed tumor growth in murine xenograft tumor models.
CD31↑, Platelet endothelial cell adhesion molecule (PECAM-1/CD31) was significantly increased after HBOT
P53↓, p53 proteins in A549 cells were first downregulated by HBOT and then rebounded to basal level after 6 h of HBOT, but not Beas-2B cells
Dose∅, HBOT in cancer therapy without any combined treatment in the manner of 2.5 ATA/90 min/day in 2 weeks after 45 days of tumor transfer.
other↑, HBOT significantly improved tumor hypoxia after 14 days
Apoptosis↑, HBOT induced apoptosis in A549 tumor transferred SCID mice
Hif1a↑, increased HIF-1α protein in A549 cells, not Beas-2B cells(normal cells)
selectivity↑, increased HIF-1α protein in A549 cells, not Beas-2B cells(normal cells)

2300-

QC,

Flavonoids Targeting HIF-1: Implications on Cancer Metabolism

Review,

Var,

AntiTum↑, Quercetin exerts promising anti-tumor effects via the regulation of various cancer signaling pathways
Hif1a↓, Quercetin inhibited HIF-1 transcriptional activity in the HCT116 colon cancer cell line
*Hif1a↑, On the contrary, quercetin increased the accumulation of HIF-1α in healthy cells
Glycolysis↓, Quercetin inhibited glycolysis and proliferation of glycolysis-dependent hepatocellular carcinoma (SMMC-7721 and Bel-7402) cells by downregulating HKII;
HK2↓,
PDK3↓, quercetin inhibited PDK3 in hepatocellular carcinoma (HepG2) and lung cancer (A549) cells
PFKP?, The ability of quercetin to impair PFKP-LDHA signaling

2303-

QC,

doxoR,

Quercetin greatly improved therapeutic index of doxorubicin against 4T1 breast cancer by its opposing effects on HIF-1α in tumor and normal cells

in-vitro,

BC,

4T1

100uM

51.42 uM

in-vivo,

NA,

quercetin 100 mg/kg day or DOX 5 mg/kg

mice

cardioP↑, Quercetin had better cardioprotective and hepatoprotective activities.
hepatoP↑,
TumCG↓, In vivo, quercetin suppressed tumor growth and prolonged survival in BALB/c mice bearing 4T1 breast cancer.
OS↑,
ChemoSen↑, quercetin enhanced therapeutic efficacy of DOX and simultaneously reduced DOX-induced toxic side effects
chemoP↑, IC50 of DOX in combination with quercetin 10 or 25 uM was increased by three- and fourfold, respectively, compared with that of DOX alone
Hif1a↓, Further study showed that quercetin suppressed intratumoral HIF-1α in a hypoxia-dependent way but increased its accumulation in normal cells
*Hif1a↑,
selectivity↑, quercetin could improve therapeutic index of DOX by its opposing effects on HIF-1α in tumor and normal cells
TumVol↓,
OS↑,

3078-

RES,

The Effects of Resveratrol on Prostate Cancer through Targeting the Tumor Microenvironment

Review,

Pca,

*ROS↓, RSV appears to be both pro- and anti-oxidant, depending on the circumstances [76]. In non-cancer tissues, RSV serves as an antioxidant [77], and therefore RSV can exert a beneficial effect on a wide variety of issues, including neuronal [78], anti-in
ROS↑, However, to cancer cells with low pH environments due to the Warburg Effect, RSV shows more pro-oxidant characteristics.
DNAdam↑, RSV can induce cancer cell death by inducing ROS accumulation, which subsequently leads to oxidative DNA damage and apoptosis
Apoptosis↑,
Hif1a↑, Wang et al. demonstrated that RSV-enhanced cancer cell death is due to the upregulation of HIF1α, which enhances ROS concentration in the TME beyond the limit for survival
Casp3↑, superoxide can activate caspases 9 and 3, and subsequently promote the release of cytochrome C
Casp9↑,
Cyt‑c↑,
Dose↝, It is important to note that low concentration of RSV can serve as a pro-oxidant that favors cell survival, and pro-apoptotic effects occur only at relatively higher RSV concentrations to stimulate superoxide production.
MMPs↓, inhibitory effect of RSV on MMPs has been shown in many cancer types, and RSV is capable of inhibiting both MMP-2 and MMP-9
MMP2↓,
MMP9↓,
EMT↓, RSV can restore the epithelial phenotype of the mesenchymal cells and inhibit the expression of EMT-related markers
E-cadherin↑, RSV can inhibit EMT by up- and downregulating E-cadherin and N-cadherin, respectively, in prostate cancer cells.
N-cadherin↓,
AR↓, RSV can repress AR function by inhibiting AR transcriptional activity

2195-

SK,

Shikonin induces ferroptosis in osteosarcomas through the mitochondrial ROS-regulated HIF-1α/HO-1 axis

in-vitro,

OS,

TumCP↓, At a low dose, Shikonin inhibits OS progression and has a excellent biosafety.
Ferroptosis↓, Shikonin induces ferroptosis in OS cel
Hif1a↑, Shikonin upregualtes HIF-1α/HO-1 axis to produce excess Fe2+ which leads to ROS accumulation on OS cell, followed by ferroptosis.
HO-1↑,
Iron↑,
ROS↑,
GSH/GSSG↓, while simultaneously reducing the GSH/GSSG ratio and GPX4 and SLC7A11 expression
GPx4↓,

2138-

TQ,

Thymoquinone has a synergistic effect with PHD inhibitors to ameliorate ischemic brain damage in mice

in-vivo,

Nor,

TQ (5 mg/kg

Male C57 mice were used to establish an ischemic stroke model by using endothelin-1

*Hif1a↑, TQ can activate the HIF-1α pathway and its downstream genes such as VEGF, TrkB, and PI3K, which in turn enhance angiogenesis and neurogenesis.
*VEGF↑,
*TrkB↑,
*PI3K↑,
*angioG↑, which in turn enhance angiogenesis and neurogenesis.
*neuroG↑,
*motorD↑, TQ has the same effect as DMOG to activate HIF-1 α and can improve motor dysfunction after ischemic stroke

2139-

TQ,

Thymoquinone regulates microglial M1/M2 polarization after cerebral ischemia-reperfusion injury via the TLR4 signaling pathway

in-vivo,

Nor,

acute ischemic stroke using a mouse middle cerebral artery ischemia-reperfusion (I/R) model.

*TLR4↓, TQ inhibits the TLR4 / NF-κB pathway to regulate microglia polarization.
*NF-kB↓,
*Inflam↓, TQ attenuates inflammation in brain I/R by affecting microglia polarization.
*Hif1a↑, TQ can activate Hif-1α to counter-regulate the TLR4 / NF-κB pathway.
*motorD↑, TQ could improve the motor deficits caused by I/R.

2283-

VitK2,

Vitamin K Contribution to DNA Damage—Advantage or Disadvantage? A Human Health Response

Review,

Var,

*ER Stress↓, protective effect of vitamin K on blood vessels, by reducing inflammation and stress ER
*toxicity↓, Natural forms of vitamin K–K1 and K2—have only a low potential for toxicity
*toxicity↑, However, K3 may demonstrate harmful potential: synthetic vitamin K3 can lead to liver damage
ROS↑, Like another quinone, doxorubicin, menadione exerts its cytotoxic effects by stimulating the generation of oxidative stress, leading to DNA damage
PI3K↑, In bladder cancer cells (T24), vitamin K2 significantly induces PI3K/Akt phosphorylation and increases expression of HIF-1α, intensifying glucose consumption and lactate formation.
Akt↑,
Hif1a↑,
GlucoseCon↑,
lactateProd↑,
ChemoSen↑, Numerous studies indicate that the K vitamins have an additive or synergistic effect on various chemotherapeutic agents.
eff↑, A strong synergism between K1 and sorafenib has been demonstrated in numerous studies
eff↑, ascorbic acid (AA), has a synergistic effect on K3 [73,122,123]. The AA/K3 association leads to an excessive increase in oxidative stress and a decrease in the potential of the mitochondrial membrane, which is a crucial trigger of tumor cell death

1214-

VitK2,

Vitamin K2 promotes PI3K/AKT/HIF-1α-mediated glycolysis that leads to AMPK-dependent autophagic cell death in bladder cancer cells

in-vitro,

Bladder,

T24/HTB-9

50 μM

in-vitro,

Bladder,

J82

Glycolysis↑, Vitamin K2 renders bladder cancer cells more dependence on glycolysis than TCA cycle
GlucoseCon↑, results suggest that Vitamin K2 is able to induce metabolic stress, including glucose starvation and energy shortage, in bladder cancer cells, upon glucose limitation.
lactateProd↑,
TCA↓, Vitamin K2 promotes glycolysis and inhibits TCA cycle in bladder cancer cells
PI3K↑,
Akt↑,
AMPK↑, Vitamin K2 remarkably activated AMPK pathway
mTORC1↓,
TumAuto↑,
GLUT1↑, Vitamin K2 stepwise elevated the expression of some glycolytic proteins or enzymes, such as GLUT-1, Hexokinase II (HK2), PFKFB2, LDHA and PDHK1, in bladder cancer T24
HK2↑,
LDHA↑, Vitamin K2 stepwise elevated the expression of some glycolytic proteins or enzymes, such as GLUT-1, Hexokinase II (HK2), PFKFB2, LDHA and PDHK1, in bladder cancer T24
ACC↓, Vitamin K2 remarkably decreased the amounts of Acetyl coenzyme A (Acetyl-CoA) in T24 cells
PDH↓, suggesting that Vitamin K2 inactivates PDH
eff↓, Intriguingly, glucose supplementation profoundly abrogated AMPK activation and rescued bladder cancer cells from Vitamin K2-triggered autophagic cell death.
cMyc↓, c-MYC protein level was also significantly reduced in T24 cells following treatment with Vitamin K2 for 18 hours
Hif1a↑, Besides, the increased expression of GLUT-1, HIF-1α, p-AKT and p-AMPK were also detected in Vitamin K2-treated tumor group
p‑Akt↑,
eff↓, 2-DG, 3BP and DCA-induced glycolysis attenuation significantly prevented metabolic stress and rescued bladder cancer cells from Vitamin K2-triggered AMPK-dependent autophagic cell death
eff↓, inhibition of PI3K/AKT and HIF-1α notably attenuated Vitamin K2-upregulated glycolysis, indicating that Vitamin K2 promotes glycolysis in bladder cancer cells via PI3K/AKT and HIF-1α signal pathways.
eff↓, (NAC, a ROS scavenger) not only alleviated Vitamin K2-induced AKT activation and glycolysis promotion, but also significantly suppressed the subsequent AMPK-dependent autophagic cell death.
eff↓, glucose supplementation not only restored c-MYC expression, but also rescued bladder cancer cells from Vitamin K2-triggered AMPK-dependent autophagic cell death
ROS↑, under glucose limited condition, the increased glycolysis inevitably resulted in metabolic stress, which augments ROS accumulation due to lack of glucose for sustained glycolysis.

Showing Research Papers: 1 to 23 of 23

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 23

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 2, GSH↑, 1, HK1↑, 1, HO-1↑, 2, NRF2↑, 2, ROS↓, 4, SIRT3↑, 1,

Metal & Cofactor Biology ⓘ

IronCh↑, 1,

Mitochondria & Bioenergetics ⓘ

MMP↑, 1, PGC-1α↑, 1,

Core Metabolism/Glycolysis ⓘ

GlucoseCon↑, 2, Glycolysis↑, 1, PDH↑, 1, PDKs↓, 1, SIRT1↑, 4,

Cell Death ⓘ

AhR↑, 1, Apoptosis↓, 1,

Transcription & Epigenetics ⓘ

Ach↑, 1, other↑, 1,

Protein Folding & ER Stress ⓘ

CHOP↓, 1, ER Stress↓, 2, PERK↓, 1,

DNA Damage & Repair ⓘ

ATM↑, 1,

Cell Cycle & Senescence ⓘ

E2Fs↑, 1,

Proliferation, Differentiation & Cell State ⓘ

CD34↑, 1, FGF↑, 1, FOXO1↑, 1, FOXO3↑, 1, Jun↑, 1, neuroG↑, 1, PI3K↑, 1,

Migration ⓘ

Ca+2↓, 1, ITGB1↑, 1, MMP2↑, 1, MMP9↑, 1, NFAM1↑, 1, NFAT↑, 2, TIMP1↑, 1, VCAM-1↓, 1,

Angiogenesis & Vasculature ⓘ

angioG↑, 4, ATF4↓, 1, Hif1a↑, 13, NO↓, 1, REL↑, 1, VEGF↑, 6, VEGFR2↑, 1,

Barriers & Transport ⓘ

BBB↑, 1, GLUT3↑, 2, GLUT4↑, 2,

Immune & Inflammatory Signaling ⓘ

CXCc↑, 1, IL2↑, 1, IL6↑, 1, Inflam↓, 3, LIF↑, 1, NF-kB↓, 1, OSM↑, 1, TLR4↓, 1,

Synaptic & Neurotransmission ⓘ

ChAT↑, 1, tau↓, 1, p‑tau↓, 1, TrkB↑, 1,

Protein Aggregation ⓘ

Aβ↓, 1,

Hormonal & Nuclear Receptors ⓘ

ARNT↑, 1,

Drug Metabolism & Resistance ⓘ

Dose↝, 1, eff↓, 1,

Clinical Biomarkers ⓘ

GutMicro↑, 1, IL6↑, 1,

Functional Outcomes ⓘ

AntiAge↑, 2, cardioP↑, 1, cognitive↑, 1, hepatoP↑, 1, memory↑, 1, motorD↑, 2, neuroP↑, 2, toxicity↓, 1, toxicity↑, 1,
Total Targets: 76

Scientific Paper Hit Count for: Hif1a, HIF1α/HIF1a

5 Alpha-Lipoic-Acid
2 Silver-NanoParticles
2 Electrical Pulses
2 Magnetic Fields
2 Quercetin
2 Thymoquinone
2 Vitamin K2
1 Allicin (mainly Garlic)
1 Celastrol
1 Ferulic acid
1 Oxygen, Hyperbaric
1 doxorubicin
1 Resveratrol
1 Shikonin

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#:2
  wNotes=on  sortOrder:rid,rpid

Hif1a Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Metal & Cofactor Biology ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Synaptic & Neurotransmission ⓘ

Protein Aggregation ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Home Page