HIF-1 Cancer Research Results

HIF-1, HIF-1 signaling: Click to Expand ⟱

Source: HalifaxProj(inhibit)

Type:

Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that plays a crucial role in cellular responses to low oxygen levels (hypoxia). It is composed of two subunits: HIF-1α and HIF-1β. Under normal oxygen conditions, HIF-1α is rapidly degraded, but in hypoxic conditions, it stabilizes, translocates to the nucleus, and dimerizes with HIF-1β to activate the transcription of various genes involved in processes such as angiogenesis, metabolism, and cell survival.
HIF-1α is often overexpressed due to the hypoxic microenvironment created by rapid tumor growth and inadequate blood supply. This upregulation allows cancer cells to adapt to low oxygen levels. HIF-1 regulates the expression of numerous target genes involved in angiogenesis (e.g., VEGF), glucose metabolism (e.g., GLUT1), cell survival, and invasion. The activation of these genes promotes tumor growth and metastasis.
However, HIF-1 is expressed in pathological conditions such as cancer and obesity.

Scientific Papers found: Click to Expand⟱

4549-

AgNPs,

Silver nanoparticles: Synthesis, medical applications and biosafety

Review,

Var,

Review,

Diabetic,

ROS↑, action mechanisms of AgNPs, which mainly involve the release of silver ions (Ag+), generation of reactive oxygen species (ROS), destruction of membrane structure.
eff↑, briefly introduce a new type of Ag particles smaller than AgNPs, silver Ångstrom (Å, 1 Å = 0.1 nm) particles (AgÅPs), which exhibit better biological activity and lower toxicity compared with AgNPs.
other↝, This method involves reducing silver ions to silver atoms 9, and the process can be divided into two steps, nucleation and growth
DNAdam↑, antimicrobial mechanisms of AgNPs includes destructing bacterial cell walls, producing reactive oxygen species (ROS) and damaging DNA structure
EPR↑, Due to the enhanced permeability and retention (EPR) effect, tumor cells preferentially absorb NPs-sized bodies than normal tissues
eff↑, Large surface area may lead to increased silver ions (Ag+) released from AgNPs, which may enhance the toxicity of nanoparticles.
eff↑, Our team prepared Ångstrom silver particles, capped with fructose as stabilizer, can be stable for a long time
TumMeta↓, AgNPs can induce tumor cell apoptosis through inactivating proteins and regulating signaling pathways, or blocking tumor cell metastasis by inhibiting angiogenesis
angioG↓, Various studies support that AgNPs can deprive cancer cells of both nutrients and oxygen via inhibiting angiogenesis
*Bacteria↓, Rather than Gram-positive bacteria, AgNPs show a stronger effect on the Gram-negative ones. This may be due to the different thickness of cell wall between two kinds of bacteria
*eff↑, In general, as particle size decreases, the antibacterial effect of AgNPs increases significantly
*AntiViral↑, AgNPs with less than 10 nm size exhibit good antiviral activity 185, 186, which may be due to their large reaction area and strong adhesion to the virus surface.
*AntiFungal↑, Some studies confirm that AgNPs exhibit good antifungal properties against Colletotrichum coccodes, Monilinia sp. 178, Candida spp.
eff↑, The greater cytotoxicity and more ROS production are observed in tumor cells exposed to high positive charged AgNPs
eff↑, Nanoparticles exposed to a protein-containing medium are covered with a layer of mixed protein called protein corona. formation of protein coronas around AgNPs can be a prerequisite for their cytotoxicity
TumCP↓, Numerous experiments in vitro and in vivo have proved that AgNPs can decrease the proliferation and viability of cancer cells.
tumCV↓,
P53↝, gNPs can promote apoptosis by up- or down-regulating expression of key genes, such as p53 242, and regulating essential signaling pathways, such as hypoxia-inducible factor (HIF) pathway
HIF-1↓, Yang et al. found that AgNPs could disrupt the HIF signaling pathway by attenuating HIF-1 protein accumulation and downstream target genes expression
TumCCA↑, Cancer cells treated with AgNPs may also show cell cycle arrest 160, 244
lipid-P↑, Ag+ released by AgNPs induces oxidation of glutathione, and increases lipid peroxidation in cellular membranes, resulting in cytoplasmic constituents leaking from damaged cells
ATP↓, mitochondrial function can be inhibited by AgNPs via disrupting mitochondrial respiratory chain, suppressing ATP production
Cyt‑c↑, and the release of Cyt c, destroy the electron transport chain, and impair mitochondrial function
MMPs↓, AgNPs can also inhibit the progression of tumors by inhibiting MMPs activity.
PI3K↓, Various studies support that AgNPs can deprive cancer cells of both nutrients and oxygen via inhibiting angiogenesis
Akt↓,
*Wound Healing↑, AgNPs exhibit good properties in promoting wound repair and bone healing, as well as inhibition of inflammation.
*Inflam↓,
*Bone Healing↑,
*glucose↓, blood glucose level of diabetic rats decreased when treated with AgNPs for 14 days and 21 days without significant acute toxicity.
*AntiDiabetic↑,
*BBB↑, The small-sized AgNPs are easy to penetrate the body and cross biological barriers like the blood-brain barrier and the blood-testis barrier

366-

AgNPs,

Silver nanoparticles inhibit the function of hypoxia-inducible factor-1 and target genes: insight into the cytotoxicity and antiangiogenesis

in-vitro,

BC,

MCF-7

 15.5ug/mL

HIF-1↓,
Hif1a↓, also decreased HIF-2α protein accumulation
VEGF↓, VEGF-A
GLUT1↓,

392-

AgNPs,

HIF-1aVEGF_mediated_angiogenesis_in_prostate_cancer_cells">Biogenic silver nanoparticles synthesized from Piper longum fruit extract inhibit HIF-1α/VEGF mediated angiogenesis in prostate cancer cells

VEGF↓,
HIF-1↓,

5356-

AL,

Therapeutic role of allicin in gastrointestinal cancers: mechanisms and safety aspects

Review,

GC,

Apoptosis↑, induction of apoptosis, inhibition of proliferation, and disruption of cancer cell signaling pathways, including the MAPK, PI3K/AKT, and NF-κB pathways.
TumCP↓,
MAPK↓,
PI3K↓,
Akt↓,
NF-kB↓,
AntiCan↑, Allicin and its other derivatives, such as diallyl disulfide (DADS) and ajoene, have been found to have strong anticancer potential both in vitro and in vivo.
ChemoSen↑, effectiveness of allicin in augmenting conventional chemotherapy and retarding tumor growth proves that allicin is one of the most efficient complementary therapies.
TumCCA↑, In liver cancer, allicin has been shown to mediate cell cycle arrest and apoptosis
Apoptosis↑,
BioAv↑, Allicin (diallyl thiosulfinate) is a compound that is generated when a garlic clove is crushed
selectivity↑, Furthermore, it has no influence on the growth of healthy intestinal cells when it causes stomach cancer cells to undergo apoptosis
TGF-β↓, Allicin can reduce the production of TGF-β2 and its receptor after directly entering gastric cancer cells.
ROS↑, It induces oxidative stress by generating reactive oxygen species (ROS), leading to DNA damage and activation of key apoptotic mediators such as phospho-p53 and p21 [81].
DNAdam↑,
p‑P53↑,
P21↑,
cycD1/CCND1↓, Additionally, cyclin D1, cyclin E, and cyclin-dependent kinases (CDKs) can all be inhibited by allicin.
cycE/CCNE↓,
CDK4↓, suppressing the CDK-4/6/cyclin D complex
CDK6↓,
MMP↓, By lowering the outer mitochondrial membrane potential (MMP), allicin raises levels of nuclear factor kappa B (NF-κB), the proapoptotic protein Bax, while decreasing the antiapoptotic protein Bcl-2, which leads to apoptosis.
NF-kB↑,
BAX↑,
Bcl-2↓,
ER Stress↑, cellular effects of allicin, including its role in inducing ER stress
Casp↑, enhancing caspase activation and apoptosis-inducing factor (AIF)-mediated cell death.
AIF↑,
Fas↑, increasing Fas receptor expression and its binding to Fas ligand (FasL), leading to apoptosis through caspase-8 and cytochrome c activation.
Casp8↑,
Cyt‑c↑,
cl‑PARP↑, leading to poly (ADP-ribose) polymerase (PARP) cleavage and DNA fragmentation.
Ca+2↑, allicin elevates intracellular free Ca2⁺ levels, causing endoplasmic reticulum (ER) stress, which plays a critical role in apoptosis induction
*NRF2↑, by activating the Nrf2 pathway via KLF9, allicin protects against arsenic trioxide-induced liver damage,
*chemoP↑, Additionally, allicin has shown promise in reducing hepatotoxicity caused by tamoxifen (TAM), a commonly used treatment for hormone-dependent breast cancer
*GutMicro↑, Shi et al. [85] found that allicin can ameliorate high-fat diet-induced obesity in mice by altering their gut microbiome.
CycB/CCNB1↑, DATS impaired cell survival in the G2 phase by significantly upregulating cyclins A2 and B1.
H2S↑, DATS can also react with the cellular thiol glutathione to create H2S gas, which can control several other cellular functions [79].
HIF-1↓, allicin treatment (40 µg/ml) for NSCLC lowers the expression of HIF-1 and HIF-2 in hypoxic cells [73]
RadioS↑, Allicin has been shown to increase the sensitivity of X-ray radiation therapy in colorectal cancer, presumably by suppressing the levels of NF-κB, IKKβ mRNA, p-NF-κB, and p-IKKβ protein expression in vitro and in vivo

257-

AL,

Cisplatin,

Allicin Overcomes Hypoxia Mediated Cisplatin Resistance in Lung Cancer Cells through ROS Mediated Cell Death Pathway and by Suppressing Hypoxia Inducible Factors

in-vitro,

NSCLC,

A549

 10μg/ml (LD) and 40μg/ml (HD) allicin for 24hr

 ~30µg/ml

ROS↑, apoptosis and autophagy pathway in A549 cells by ROS accumulation and facilitating S/G2-M phase arrest in both normoxia as well as hypoxia
HIF-1↓,
E-cadherin↑,
N-cadherin↓,
antiOx↓, ROS trigger cell death when its generation reached toxic threshold level by overcoming the antioxidant capacity of the cell and inducing irreversible oxidative modifications of lipid, protein or DNA [30, 48]
Dose↝, 10μg/ml (LD) and 40μg/ml (HD) allicin for 24hr

5502-

Ba,

An overview of pharmacological activities of baicalin and its aglycone baicalein: New insights into molecular mechanisms and signaling pathways

Review,

Var,

*AntiCan↑, antibacterial, antiviral, anticancer, anticonvulsant, anti-oxidant, hepatoprotective, and neuroprotective effects.
*antiOx↑,
*hepatoP↑,
*neuroP↑,
*ROS↓, pharmacological properties of baicalin and baicalein are due to their abilities to scavenge reactive oxygen species (ROS)
Ca+2↑, Baicalein mainly induced apoptosis through Ca+2 influx via Ca2+ release from the reticulum to cytosol dependent on phospholipase C protein
ROS↑, ROS production is associated with baicalein-induced apoptosis via Ca2+-dependent apoptosis in tongue and breast cancer cells (78, 79)
BAX↑, The level of Bax/Bcl-2 increased and caspase-3 and -9 were activated following the release of cytochrome C (80).
Casp3↑,
Casp9↑,
Cyt‑c↑,
MMP↓, In gastric cancer cells, baicalein mediated apoptosis in a dose-dependent manner through disruption of mitochondrial membrane potential
Mcl-1↓, In pancreatic cancer cells, baicalein induced apoptosis via suppression of the Mcl-1 protein.
PI3K↓, In HepG2 cells, baicalin-copper induced apoptosis through down-regulation of phosphoinositide-3 kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway
Akt↓,
mTOR↓,
BAD↓, Studies demonstrated that baicalein treatment suppressed Bad, ERK1/2 phosphorylation, and MEK1 expression both in vitro and in vivo.
ERK↓,
MEK↓,
DR5↑, Baicalein enhanced the activity of death receptor-5 (DR5) in prostate cancer PC3 cells.
Fas↑, baicalin is the active ingredient that acts as Fas ligand and caused up-regulation of Fas protein (89).
TumMeta↓, Baicalin/baicalein not only induced apoptosis in cancer cells but also suppressed metastasis.
EMT↓, both baicalin and baicalein inhibited epithelial-mesenchymal transition (EMT) through the suppression of TGF-β in breast epithelial cells through the NF-κB pathway (92).
SMAD4↓, baicalein suppressed metastasis in gastric cancer through inactivation of the Smad4/TGF-β pathway (93).
TGF-β↓,
MMP9↓, baicalin and baicalein inhibition of the expression level of matrix metalloproteinases (MMP) such as MMP-9 and MMP-2 in liver, breast, lung, ovarian, gastric, and colorectal cancers and glioma
MMP2↓,
HIF-1↓, Baicalin attenuated lung metastasis through inhibition of hypoxia-inducible factor (HIF)
12LOX↓, Baicalein acts as an anticancer agent via inhibiting 12-lipooxygenase (12-LOX),

5250-

Ba,

Exploring baicalein: A natural flavonoid for enhancing cancer prevention and treatment

Review,

Var,

Apoptosis↑, Baicalein is thought to prevent cancer progression by inducing apoptosis, autophagy, and genome instability, and its ability to promote chemo-potentiation, anti-metastatic effects, and regulate specific signalling molecules and transcription factors.
TumAuto↑,
DNAdam↑,
*antiOx↑, Baicalein has already been proven to be a radical scavenger that acts as an antioxidant [14,15
Inflam↓, it can also reduce inflammation [16] and act as an E2 prostaglandin inhibitor [17].
PGE2↓,
TumCCA↑, Baicalein properties prevent cell proliferation, induce apoptosis, autophagy, cell cycle arrest, cancer cell migration and invasion, and decrease angiogenesis [18,19].
TumCMig↓,
TumCI↓,
angioG↓,
selectivity↑, Furthermore, some studies have suggested that baicalein has a lower toxicity on normal cells than cancer cells, indicating some selectivity for cancer cells.
ChemoSen↑, the current review emphasises baicaleins' synergistic potential with other chemotherapeutic agents
HIF-1↓, baicalein against ovarian cancer by demonstrating that it can limit tumour cell viability by downregulating the expression of cancer-promoting genes such as HIF-1, cMyc, NFkB, and VEGF
cMyc↓,
NF-kB↓,
VEGF↓,
P53↑, Baicalein has been shown to activate p53, a tumour suppressor protein that regulates cell growth and division [26].
MMP2↓, anticancer properties of baicalein are mediated through various molecular mechanisms, including inhibition of MMP-2;
CSCs↓, inhibition of cancer stem cells
Bcl-xL↓, after bladder cancer cells were treated with baicalein, the expression of antiapoptotic genes (Bcl2, Bcl-xL, XIAP, and survivin) was reduced, and cell viability was decreased [38].
XIAP↓,
survivin↓,
tumCV↓,
Casp3↑, upregulating the expression of caspase-3 and caspase-8 and decreased the BCL-2/BAX ratio [16]
Casp8↑,
Bax:Bcl2↑,
Akt↓, in lung cancer cells, apoptosis was induced through the downregulation of the Akt/mTOR signalling pathway [25].
mTOR↓,
PCNA↓, baicalein treatment promoted apoptosis in mice with U87 gliomas by downregulating PCNA expression, enhancing the expression of caspase-3 and caspase-9 and improving the Bax/Bcl-2 ratio
MMP↓, baicalein treatment of lung cancer cells caused a collapse of the mitochondrial membrane potential (MMP), an increase in ROS generation, and enhanced PARP, caspase 3, and caspase 9 cleavage,
ROS↑,
PARP↑,
Casp9↑,
BioAv↑, Baicalein has been found to enhance the cytotoxicity and bioavailability of certain cancer therapy drugs when combined [85]
eff↑, combination of baicalein with silymarin differentially decreased the viability of HepG2 cells, enhanced the proportion of cells in the G0/G1 phase, upregulated tumour suppressors such as Rb and p53 and CDK inhibitors, and downregulated cyclin D1, cyc
P-gp↓, By inhibiting P-glycoprotein (P-gp), baicalein can increase the accumulation of chemotherapeutic drugs within cancer cells [21]
BioAv↑, selenium–baicalein nanoparticles as a targeted therapeutic strategy for NSCLC. This strategy significantly improves the bioavailability of baicalein through several mechanisms.
selectivity↑, ome studies have suggested that baicalein has a lower toxicity on normal cells than cancer cells, indicating some selectivity for cancer cells

696-

Bor,

Nothing Boring About Boron

Review,

Var,

>3mg

upper intake level (UL) of 20 mg/d

*hs-CRP↓, reduces levels of inflammatory biomarkers, such as high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor μ (TNF-μ);
*TNF-α↓,
*SOD↑, raises levels of antioxidant enzymes, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase
*Catalase↑,
*GPx↑,
*cognitive↑, improves the brains electrical activity, cognitive performance, and short-term memory for elders; restricted boron intake adversely affected brain function and cognitive performance.
*memory↑, In humans, boron deprivation (<0.3 mg/d) resulted in poorer performance on tasks of motor speed and dexterity, attention, and short-term memory.
*Risk↓, Boron-rich diets and regions where the soil and water are rich in boron correlate with lower risks of several types of cancer, including prostate, breast, cervical, and lung cancers.
*SAM-e↑,
*NAD↝, Boron strongly binds oxidized NAD+,76 and, thus, might influence reactions in which NAD+ is involved
*ATP↝,
*Ca+2↝, Because of its positive charge, magnesium stabilizes cell membranes, balances the actions of calcium, and functions as a signal transducer
HDAC↓, some boronated compounds are histone deacetylase inhibitors
TumVol↓,
IGF-1↓, expression of IGF-1 in the tumors was significantly reduced by boron treatment
PSA↓, Boronic acid has been shown to inhibit PSA activity.
Cyc↓, boric acid inhibits the growth of prostate-cancer cells both by decreasing expression of A-E cyclin
TumCMig↓,
*serineP↓, Boron exists in the human body mostly in the form of boric acid, a serine protease inhibitor.
HIF-1↓, shown to greatly inhibit hypoxia-inducible factor (HIF) 1
*ChemoSideEff↓, An in vitro study found that boric acid can help protect against genotoxicity and cytotoxicity that are induced in lymphocytes by paclitaxel
*VitD↑, greater production of 25-hydroxylase, and, thus, greater potential for vitamin-D activation
*Mag↑, Boron significantly improves magnesium absorption and deposition in bone
*eff↑, boron increases the biological half-life and bioavailability of E2 and vitamin D.
Risk↓, risk of prostate cancer was 52% lower in men whose diets supplied more than 1.8 mg/d of boron compared with those whose dietary boron intake was less than or equal to 0.9 mg/d.
*Inflam↓, As research into the chemistry of boron-containing compounds has increased, they have been shown to be potent antiosteoporotic, anti-inflammatory, and antineoplastic agents
*neuroP↑, In addition, boron has anti-inflammatory effects that can help alleviate arthritis and improve brain function and has demonstrated such significant anticancer
*Calcium↑, increase serum levels of estradiol and calcium absorption in peri- and postmenopausal women.
*BMD↑, boron stimulates bone growth in vitamin-D deficient animals and alleviates dysfunctions in mineral metabolism characteristic of vitamin-D deficiency
*chemoP↑, may help ameliorate the adverse effects of traditional chemotherapeutic agents. boric acid can help protect against genotoxicity and cytotoxicity that are induced in lymphocytes by paclitaxel, an anticancer drug commonly used to treat breast, ovarian
AntiCan↑, demonstrated preventive and therapeutic effects in a number of cancers, such as prostate, cervical, and lung cancers, and multiple and non-Hodgkin’s lymphoma
*Dose↑, only an upper intake level (UL) of 20 mg/d for individuals aged ≥ 18 y.
*Dose↝, substantial number of articles showing benefits support the consideration of boron supplementation of 3 mg/d for any individual who is consuming a diet lacking in fruits and vegetables
*BMPs↑, Boron was also found to increase mRNA expression of alkaline phosphatase and bone morphogenetic proteins (BMPs)
*testos↑, 1 week of boron supplementation of 6 mg/d, a further study by Naghii et al20 of healthy males (n = 8) found (1) a significant increase in free testosterone,
angioG↓, Inhibition of tumor-induced angiogenesis prevents growth of many types of solid tumors and provides a novel approach for cancer treatment; thus, HIF-1 is a target of antineoplastic therapy.
Apoptosis↑, Cancer cells, however, commonly overexpress sugar transporters and/or underexpress borate export, rendering sugar-borate esters as promising chemopreventive agents
*selectivity↑, In normal cells, the 2 latter, cell-destructive effects do not occur because the amount of borate present in a healthy diet, 1 to 10 mg/d, is easily exported from normal cells.
*chemoPv↑, promising chemopreventive agents

1416-

Bos,

Anti-cancer properties of boswellic acids: mechanism of action as anti-cancerous agent

Review,

NA,

5LO↓,
TumCCA↑, G0/G1 phase
LC3B↓, reduced the expression of LC3A/B-I and LC3A/B-II,
PI3K↓,
Akt↓,
Glycolysis↓,
AMPK↑,
mTOR↓,
Let-7↑,
COX2↓, methanolic extract decreased the expression of cyclooxygenase-2 gene
VEGF↓,
CXCR4↓,
MMP2↓,
MMP9↓,
HIF-1↓,
angioG↓,
TumCP↓,
TumCMig↓,
NF-kB↓,

140-

CUR,

Curcumin inhibits cancer-associated fibroblast-driven prostate cancer invasion through MAOA/mTOR/HIF-1α signaling

in-vitro,

Pca,

PC3

 25 μM

CAFs/TAFs↓, curcumin abrogated CAF-induced invasion and EMT, and inhibited ROS production and CXCR4 and IL-6 receptor expression in prostate cancer cells
EMT↓,
ROS↓, We found that curcumin abolished the CAF-derived CM-induced ROS production and CXCR4 and IL-6 receptor expression in PC3 cells
CXCR4↓,
IL6↓,
MAOA↓, inhibiting MAOA/mTOR/HIF-1α signaling, thereby supporting the therapeutic effect of curcumin in prostate cancer.
mTOR↓,
HIF-1↓,

19-

Deg,

Deguelin inhibits proliferation and migration of human pancreatic cancer cells in vitro targeting hedgehog pathway

in-vitro,

PC,

Bxpc-3

in-vitro,

PC,

PANC1

 0-20uM-1wk

HH↓, The activation of the hedgehog (Hh) signaling pathway, as well as matrix metalloproteinases (MMP)-2 and MMP-9, was suppressed by deguelin.
Gli1↓,
PTCH1↓,
Sufu↓,
MMP2↓, Deguelin downregulates MMP-2 and MMP-9 in Bxpc-3 and Panc-1 cells
MMP9↓,
PI3K/Akt↓,
HIF-1↓,
VEGF↓,
IKKα↓,
NF-kB↓,
EMT↓,
AMPK↑,
mTOR↓,
survivin↓,
TumCG↓, Deguelin treatment was observed to inhibit growth and induce apoptosis in two PC cell lines (Bxpc-3 and Panc-1)
Apoptosis↑,
TumCMig↓, Deguelin inhibits migration and invasion of PC cells
TumCI↓,

682-

EGCG,

Suppressive Effects of EGCG on Cervical Cancer

Review,

NA,

E7↓,
E6↓,
PI3K/Akt↓,
P53↑,
p27↑,
P21↑,
CDK2↓,
mTOR↓,
HIF-1↓,
IGF-1↓,
EGFR↓,
ERK↓, ERK1/2
VEGF↓,

950-

EMD,

Emodin Decreases Hepatic Hypoxia-Inducible Factor-1[Formula: see text] by Inhibiting its Biosynthesis

in-vivo,

NA,

mice

in-vitro,

Liver,

HepG2

modin inhibited <span class="wphighlight">HIF-1</span> expression in human HepG2 hepatic cells

HIF-1↓, emodin inhibited obesity-induced HIF-1 (liver and muscle, not kidney or in fat)

845-

Gra,

A Review on Annona muricata and Its Anticancer Activity

Review,

NA,

GlucoseCon↓, decreased glucose absorption
ATP↓,
HIF-1↓,
GLUT1↓,
GLUT4↓,
HK2↓,
LDHA↓,
ERK↓,
Akt↓,
Apoptosis↑,
NF-kB↓,
ROS↑, increases ROS production
Bax:Bcl2↑,
MMP↓,
Casp3↑,
Casp9↑,
p‑JNK↓,

973-

LT,

Luteolin impairs hypoxia adaptation and progression in human breast and colon cancer cells

in-vitro,

CRC,

HCT116

in-vitro,

BC,

MDA-MB-231

Apoptosis↑,
necrosis↑,
TumAuto↑,
HIF-1↓,

194-

MF,

Electromagnetic Field as a Treatment for Cerebral Ischemic Stroke

Review,

Stroke,

*BAD↓,
*BAX↓,
*Casp3↓,
*Bcl-xL↑,
*p‑Akt↑,
*MMP9↓, EMF significantly decreased levels of IL-1β and MMP9 in the peri-infarct area at 24 h and 3rd day of the experiment
*p‑ERK↑, ERK1/2
*HIF-1↓,
*ROS↓, n a similar experiment, ELF-MF (50 Hz/1 mT) increased cell viability and decreased intracellular ROS/RNS in mesenchymal stem cells submitted to OGD conditions and 3 h ELF-MF exposure
*VEGF↑,
*Ca+2↓,
*SOD↑,
*IL2↑,
*p38↑,
*HSP70/HSPA5↑,
*Apoptosis↓, PEMF decreased apoptosis
*ROS↓, Nevertheless, in the presence of ischemia, EMF decreased NO and ROS concentrations.
*NO↓,

5254-

NCL,

The magic bullet: Niclosamide

Review,

Var,

Wnt↓, In particular, niclosamide inhibits multiple oncogenic pathways such as Wnt/β-catenin, Ras, Stat3, Notch, E2F-Myc, NF-κB, and mTOR and activates tumor suppressor signaling pathways such as p53, PP2A, and AMPK.
β-catenin/ZEB1↓,
RAS↓,
STAT3↓,
NOTCH↓,
E2Fs↓,
mTOR↓,
eff↑, Moreover, niclosamide potentially improves immunotherapy by modulating pathways such as PD-1/PDL-1.
PD-1↓,
PD-L1↓, primarily through PD-L1 ligand downregulation in cancer cells.
BioAv↝, The original pharmacokinetics study showed that the maximal serum concentration can reach 0.25-6.0ug/ml (0.76-18.34 µM) following administration of a single 2g dose (11).
toxicity↓, a strong safety profile and tolerability in humans.
BioAv↑, A potential solution to the aforementioned challenge is niclosamide ethanolamine (NEN), a salt form of niclosamide that also functions as a mitochondrial uncoupler with a superior safety profile and enhanced bioavailability
ETC↑, NEN activates the ETC to boost NADH oxidation, thereby leading to an increased intracellular NAD+/NADH ratio and driving the TCA cycle forward.
NADH:NAD↓,
TCA↑,
Warburg↓, leading to a reversal of the Warburg effect and the induction of cellular differentiation
Diff↑,
AMPK↑, figure 3
P53↑,
PP2A↑,
HIF-1↓,
KRAS↓,
Myc↓,
RadioS↑, leading to a reversal of the Warburg effect and the induction of cellular differentiation
ChemoSen↑, Niclosamide has shown synergistic anti-tumor effects with a broad spectrum of chemotherapy drugs.
Dose↝, In this trial, either 500mg or 1000mg niclosamide was given three times daily to patients. However, the maximal plasma concentration ranged from 35.7–82 ng/mL (0.1µM-0.25 µM), a range that failed to be consistently above the minimum effective concent
Dose↑, In contrast, the ongoing clinical trial NCT02807805 is administering 1200 mg of reformulated orally bioavailable niclosamide orally (PO) three times daily to patients, resulting in 0.21µM-0.723 plasma niclosamide concentrations exceeding the therape

4626-

OLE,

A Comprehensive Review on the Anti-Cancer Effects of Oleuropein

Review,

Var,

Risk↓, Many studies have shown that olive oil consumption reduces the incidence of cancer of any kind, particularly breast and digestive system tumors
Dose↑, Some studies suggest that 7.5 g of Ole for a 70 kg human may have an anti-tumor effect by decreasing mitosis and by increasing apoptosis [9,10], but this high dose may be impossible to achieve
TumCP↓, Ole’s anti-proliferative action has been established in numerous research using MCF-7 cell lines
NF-kB↓, Ole (100 µM) was found to suppress the nuclear factor-light-chain-enhancer of activated B (NF-kB) and its downstream targets cyclin D1 and cyclooxygenase-2 (COX2) in the MDA-MB-231 breast cancer cell line.
COX2↓,
Akt↓, Ole (100 µM) was found to suppress the nuclear factor-light-chain-enhancer of activated B (NF-kB) and its downstream targets cyclin D1 and cyclooxygenase-2 (COX2) in the MDA-MB-231 breast cancer cell line.
P53↑, Oleuropein raises the expression of the proapoptotic proteins p53 and Bax while decreasing the expression of the antiapoptotic proteins Bcl-2 and HIF-1.
BAX↑,
Bcl-2↓,
HIF-1↓,
ROS↑, Ole promotes cell damage and functions as a pro-oxidant, which contributes to cell death, according to studies on in vitro MCF-7 breast cancer cells. The activation of reactive oxygen species (ROS) is responsible for this pro-oxidant property
HO-1↑, Furthermore, an increase in the heme-oxygenase 1 (HO-1) enzyme at doses of 100 and 500 µM, which is a potent antioxidant containing thiol groups, is thought to be the mechanism by which the antioxidant action is exclusive to BPH-1 cells
chemoP↑, Ole’s antioxidant action has a chemo-protective effect, as evidenced by the fact that it slows colon cancer progression
TumCCA↑, This dual impact could lead to an increase in intracellular ROS, which could lead to cell arrest
FASN↓, Ole’s anti-cancer benefits could be attributed to its capacity to inhibit the fatty acid synthase enzyme (FASN)

39-

QC,

A Comprehensive Analysis and Anti-Cancer Activities of Quercetin in ROS-Mediated Cancer and Cancer Stem Cells

Analysis,

NA,

ROS↑, production of ROS in both cancer, and cancer stem cells,
GSH↓, By directly reducing the intracellular pool of glutathione (GSH), QC can influence ROS metabolism
IL6↓, QC is its ability to inhibit inflammatory mediators including IFN-γ, IL-6, COX-2, IL-8, iNOS, TNF-α, and many other cancer inflammatory mechanisms
COX2↓,
IL8↓,
iNOS↓,
TNF-α↓,
MAPK↑, quercetin-3-methyl ether stopped the growth of cancer in the esophagus by blocking the Akt/mTOR/P70S6k and MAPK pathways, which are important for the growth of cancer
ERK↑,
SOD↑,
ATP↓,
Casp↑,
PI3K/Akt↓,
mTOR↓,
NOTCH1↓,
Bcl-2↓,
BAX↑,
IFN-γ↓,
TumCP↓, QC directly involves inducing apoptosis and/or the cell cycle arrest process, and also inhibits the propagation of rapidly proliferating cells
TumCCA↑,
Akt↓, quercetin-3-methyl ether stopped the growth of cancer in the esophagus by blocking the Akt/mTOR/P70S6k and MAPK pathways, which are important for the growth of cancer
P70S6K↓,
*Keap1↓,
*GPx↑, inhibiting its negative regulator, Keap1, resulting in Nrf-2 nuclear translocation [86]. This results in the production and activation of enzymes namely GPX, CAT, heme oxygenase 1 (HO-1), peroxiredoxin (PRX)
*Catalase↑,
*HO-1↑,
*NRF2↑,
NRF2↑, The effect of QC on nuclear translocation of Nrf-2 in a time-dependent manner, and increased expression level in HepG2, MgM (malignant mesothelioma) MSTO-211H, and H2452 cells at mRNA and protein quantity has been reported recently
eff↑, quercetin coupled with gold nanoparticles promoted apoptosis by inhibiting the EGFR/P13K/Akt-mediated pathway
HIF-1↓, Quercetin has been shown to suppress the Akt-mTOR pathway and hypoxia-induced factor 1 signaling pathway in gastric cancer cells, resulting in preventative autophagy

3323-

SIL,

Anticancer therapeutic potential of silibinin: current trends, scope and relevance

Review,

Var,

Inflam↓, Silibinin has been shown to have anti-inflammatory, anti-angiogenic, antioxidant, and anti-metastatic properties
angioG↓,
antiOx↑,
TumMeta↓,
TumCP↓, silibinin helps in preventing proliferation of the tumor cells, initiating the cell cycle arrest, and induce cancer cells to die
TumCCA↑,
TumCD↑,
α-SMA↓, figure
p‑Akt↓,
p‑STAT3↓,
COX2↓,
IL6↓,
MMP2↓,
HIF-1↓,
Snail↓,
Slug↓,
Zeb1↓,
NF-kB↓,
p‑EGFR↓,
JAK2↓,
PI3K↓,
PD-L1↓,
VEGF↓,
CDK4↓,
CDK2↓,
cycD1/CCND1↓,
E2Fs↓,

3104-

VitC,

Pro- and Antioxidant Effects of Vitamin C in Cancer in correspondence to Its Dietary and Pharmacological Concentrations

*antiOx↑, Vitamin C is an antioxidant that may scavenge reactive oxygen species preventing DNA damage and other effects important in cancer transformation
*ROS↓,
*DNAdam↓,
ROS↑, High pharmacological doses of vitamin C may induce prooxidant effects, detrimental for cancer cells.
TET1↑, Vitamin C may change the metabolomic and epigenetic profiles of cancer cells, and activation of ten-eleven translocation (TET) proteins and downregulation of pluripotency factors by the vitamin may eradicate cancer stem cells.
CSCs↓,
HIF-1↓, Vitamin C induces degradation of hypoxia-inducible factor, HIF-1, essential for the survival of tumor cells in hypoxic conditions
BioAv↑, Flavonoids may modulate bioavailability of vitamin C. Animal studies with flavonoid-rich extracts or purified plant flavonoids showed an enhanced uptake of vitamin C when it was administered together with flavonoids
selectivity↑, Chen et al. demonstrated that intravenous administration of ascorbic acid at high concentrations was toxic for many types of cancer cells in xenografts in mice with no effect on normal cells

961-

Zinc Downregulates HIF-1α and Inhibits Its Activity in Tumor Cells In Vitro and In Vivo

in-vitro,

RCC,

RCC4

vitro+vivo,

GBM,

U373MG

in-vitro,

Nor,

HUVECs

Hif1a↓, but not effective in RCC line
HIF-1↓,
VEGF↓,
TumCI↓,

Showing Research Papers: 1 to 22 of 22

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 22

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 3, Catalase↑, 2, GPx↑, 2, HO-1↑, 1, Keap1↓, 1, NRF2↑, 2, ROS↓, 4, SAM-e↑, 1, SOD↑, 2,

Mitochondria & Bioenergetics ⓘ

ATP↝, 1,

Core Metabolism/Glycolysis ⓘ

glucose↓, 1, NAD↝, 1,

Cell Death ⓘ

p‑Akt↑, 1, Apoptosis↓, 1, BAD↓, 1, BAX↓, 1, Bcl-xL↑, 1, Casp3↓, 1, p38↑, 1,

Protein Folding & ER Stress ⓘ

HSP70/HSPA5↑, 1,

DNA Damage & Repair ⓘ

DNAdam↓, 1,

Proliferation, Differentiation & Cell State ⓘ

p‑ERK↑, 1,

Migration ⓘ

Ca+2↓, 1, Ca+2↝, 1, MMP9↓, 1, serineP↓, 1,

Angiogenesis & Vasculature ⓘ

HIF-1↓, 1, NO↓, 1, VEGF↑, 1,

Barriers & Transport ⓘ

BBB↑, 1,

Immune & Inflammatory Signaling ⓘ

IL2↑, 1, Inflam↓, 2, TNF-α↓, 1, VitD↑, 1,

Hormonal & Nuclear Receptors ⓘ

testos↑, 1,

Drug Metabolism & Resistance ⓘ

Dose↑, 1, Dose↝, 1, eff↑, 2, selectivity↑, 1,

Clinical Biomarkers ⓘ

BMD↑, 1, BMPs↑, 1, Calcium↑, 1, GutMicro↑, 1, hs-CRP↓, 1, Mag↑, 1, VitD↑, 1,

Functional Outcomes ⓘ

AntiCan↑, 1, AntiDiabetic↑, 1, Bone Healing↑, 1, chemoP↑, 2, chemoPv↑, 1, ChemoSideEff↓, 1, cognitive↑, 1, hepatoP↑, 1, memory↑, 1, neuroP↑, 2, Risk↓, 1, Wound Healing↑, 1,

Infection & Microbiome ⓘ

AntiFungal↑, 1, AntiViral↑, 1, Bacteria↓, 1,
Total Targets: 61

Scientific Paper Hit Count for: HIF-1, HIF-1 signaling

3 Silver-NanoParticles
2 Allicin (mainly Garlic)
2 Baicalein
1 Cisplatin
1 Boron
1 Boswellia (frankincense)
1 Curcumin
1 Deguelin
1 EGCG (Epigallocatechin Gallate)
1 Emodin
1 Graviola
1 Luteolin
1 Magnetic Fields
1 Niclosamide (Niclocide)
1 Oleuropein
1 Quercetin
1 Silymarin (Milk Thistle) silibinin
1 Vitamin C (Ascorbic Acid)
1 Zinc

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#:142  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

HIF-1 Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

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 ⓘ

Synaptic & Neurotransmission ⓘ

Protein Aggregation ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Protein Folding & ER Stress ⓘ

DNA Damage & Repair ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

Home Page