SREBP2 Cancer Research Results

SREBP2, Sterol Regulatory Element-Binding Protein 2: Click to Expand ⟱
Source:
Type:
Sterol Regulatory Element-Binding Protein 2 (SREBP-2)
SREBP-2 is a key transcription factor that primarily regulates cholesterol biosynthesis and uptake. In recent years, its dysregulation has been linked to altered lipid metabolism within tumors, potentially affecting tumor growth, metastasis, and response to treatment.
– SREBP-2) is a pivotal transcriptional factor in cholesterol metabolism.
– SREBP-2 controls the transcription of genes involved in cholesterol biosynthesis and uptake (e.g., HMG-CoA reductase, LDL receptor).
– Cancer cells may upregulate SREBP-2 as part of metabolic rewiring to meet the demands of rapid proliferation.

– Elevated SREBP-2 expression has been observed in several tumor types, including prostate, breast, and hepatocellular carcinoma.
– High expression levels are sometimes associated with aggressive tumor phenotypes, increased proliferative capacity, and a higher incidence of metastasis.

• SREBP-2 plays a critical role in maintaining lipid homeostasis, and its dysregulation in cancer can contribute to tumor growth and aggressiveness.
• Elevated SREBP-2 expression is generally associated with enhanced tumor cell proliferation, increased risk of metastasis, and in some instances, a poorer prognosis.
Scientific Papers found: Click to Expand⟱
1539- Api,  LT,    Dietary flavones counteract phorbol 12-myristate 13-acetate-induced SREBP-2 processing in hepatic cells
- in-vitro, Liver, HepG2
SREBP2↓, ecreased transcription of SREBP-2 upon the apigenin treatment
eff↑, 25 lM of both flavones could significantly bring down the induced pMEK and pERK.
p‑MEK↓,
p‑ERK↓,

4988- ATV,  Dipy,    Repurposing of the Cardiovascular Drug Statin for the Treatment of Cancers: Efficacy of Statin–Dipyridamole Combination Treatment in Melanoma Cell Lines
- in-vivo, Melanoma, NA
HMGCR↓, Metastatic melanoma has a very poor prognosis. Statins, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) inhibitors, are cholesterol-lowering agents with a potential for cancer treatment.
SREBP2↑, The inhibition of HMGCR by statins, however, induces feedback, which paradoxically upregulates HMGCR expression via sterol regulatory element-binding protein-2 (SREBP2)
SREBP2↓, Dipyridamole, an antiplatelet agent, is known to inhibit SREBP2 upregulation.
AntiAg↑,

4985- ATV,  Dipy,    Repurposing of the Cardiovascular Drug Statin for the Treatment of Cancers: Efficacy of Statin-Dipyridamole Combination Treatment in Melanoma Cell Lines
- in-vivo, Melanoma, SK-MEL-28 - in-vitro, BC, MDA-MB-435
HMG-CoA↓, inhibition of HMGCR by statins, however, induces feedback, which paradoxically upregulates HMGCR expression via sterol regulatory element-binding protein-2 (SREBP2)
SREBP2↓, Dipyridamole, an antiplatelet agent, is known to inhibit SREBP2 upregulation.
eff↑, the inexpensive and frequently prescribed statin–dipyridamole combination therapy may lead to new developments in the treatment of melanoma and may potentiate the effects of vemurafenib for the targeted therapy of BRAF V600E-mutation bearing melanoma
HMGCR⇅, Atorvastatin Upregulates HMGCR mRNA Expression in a Dose-Dependent Manner While Dipyridamole Tends to Downregulate It
ChemoSen↑, combining conventional chemo- and/or targeted therapies with new drugs to improve therapeutic outcomes

6223- CUR,    Curcumin Rewires the Tumor Metabolic Landscape: Mechanisms and Clinical Prospects
- Review, Var, NA
Ferroptosis↑, including the induction of ferroptosis by regulating the SLC7A11/GPX4 axis
GutMicro↑, and modulating gut microbiota metabolism. I
Akt↓, it inhibits pro-tumorigenic signals such as Akt/mTOR, NF-κB, Wnt/β-catenin, and STAT3, thereby blocking tumor proliferation, invasion, and metastasis
mTOR↓,
NF-kB↓,
Wnt↓,
β-catenin/ZEB1↓,
STAT3↓,
TumCP↓,
TumCI↓,
TumMeta↓,
AMPK↑, activates tumor-suppressive and cytoprotective pathways, including AMPK, p53, and nuclear factor erythroid 2-related factor 2 (Nrf2), which induce cell cycle arrest and apoptosis
P53↑,
NRF2↑,
TumCCA↑,
Apoptosis↑,
Casp↑, activation of the Caspase cascade
GPx4↓, as well as ferroptosis by inhibiting the solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) axis [5]
DNMTs↓, inhibiting epigenetic regulatory mechanisms such as DNMTs and HDACs.
HDAC↓,
VEGF↓, inhibiting VEGF signaling and enhances the immune microenvironment by improving T cell and NK cell function
Imm↑,
NK cell↑,
Warburg↓, Curcumin effectively reverses the Warburg effect and interferes with glucose metabolism by targeting HIF-1α and inhibiting key enzymes, including hexokinase 2 (HK2), pyruvate kinase M2 (PKM2), and lactate dehydrogenase A (LDHA)
Hif1a↓,
HK2↓,
PKM2↓,
LDHA↓,
GLUT1↓, as well as the functions of glucose transporter 1 (GLUT1) and monocarboxylate transporters (MCTs) [12].
MCT1↓,
AMPK↑, curcumin activates signaling pathways such as AMPK, downregulates fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD1),
FASN↓,
SCD1↓,
GLS↓, Curcumin extensively intervenes in amino acid metabolism by inhibiting the activity of glutaminase (GLS), ornithine decarboxylase (ODC), and other enzymes,
Apoptosis↑, inducing apoptosis through mechanisms such as disrupting the electron transport chain, reducing membrane potential, and promoting the generation of reactive oxygen species (ROS)
ETC↓,
MMP↓,
ROS↑,
lipid-P↑, curcumin induces lipid peroxidation and collapses redox homeostasis, thereby activating the ferroptosis program [
ChemoSen↑, blocking invasion and metastasis, and enhancing chemosensitivity.
PDK1↓, In hypoxic pancreatic cancer cells, curcumin downregulates the expression of GLUT1, HK2, LDHA, and PDK1 by inhibiting the Beclin1/HIF-1α axis, which results in reduced ATP production and inhibited cell proliferation [
Beclin-1↓,
ATP↓,
Glycolysis↓, inhibiting glycolysis
GlucoseCon↓, decreased glucose uptake and increased lactate production
lactateProd↑,
MMPs↓, reduces MMP, GSH, and G6PD activities
GSH↓, inhibition of SLC7A11 to limit GSH synthesis, thereby triggering the collapse of the antioxidant defense system
G6PD↓,
OXPHOS↓, downregulate OXPHOS and glycolysis activities
SREBP2↓, curcumin treatment leads to a marked downregulation of the mRNA expression of SREBP and its target genes. inhibiting the expression of NPC1L1, SREBP-2, and HNF1α
COX2↓, curcumin exerts anti-tumor effects by downregulating the expression of NF-κB, COX-2, and AP-1
AP-1↓,
NADH↓, decreased GPx4 and FSP1 expression, induced ferroptosis by inhibiting GSH-GPx4 and FSP1-CoQ 10-NADH pathways
NRF2↑, it inhibits GPX4 and activates Nrf2 and heme oxygenase-1 (HO-1). This results in an abnormal accumulation of intracellular Fe2+, ROS, lipid peroxides, and malondialdehyde (MDA), along with a depletion of GSH
HO-1↑,
Iron↑,
MDA↑,
*ROS↓, studies have demonstrated that the topical application of curcumin on the skin exerts antitumor effects by synergistically downregulating COX-2 and ODC activities, alleviating oxidative damage, and concurrently inhibiting inflammatory proliferation i
*Inflam↓,

3246- EGCG,    Epigallocatechin gallate suppresses hepatic cholesterol synthesis by targeting SREBP-2 through SIRT1/FOXO1 signaling pathway
- in-vitro, Nor, NA
*MDA↓, EGCG remarkably diminished MDA content in the liver with hypercholesterolemia and increased T-AOC and SOD activity.
*SOD↑,
*SIRT1↑, EGCG activated SIRT1 and increased FOXO1 expression
*FOXO1↑,
*SREBP2↓, EGCG increased FOXO1 expression, and decrease SREBP-2 expression

6820- EMD,    The Health Benefits of Emodin, a Natural Anthraquinone Derived from Rhubarb—A Summary Update
- Review, Nor, NA - Review, Arthritis, NA - Review, AD, NA
*diuretic↑, Emodin has a wide range of biological activities, including diuretic, antibacterial, antiulcer, anti-inflammatory, anticancer and antinociceptive.
*Bacteria↓,
*Inflam↓,
AntiCan↑,
TumCP↓, emodin inhibits processes of neoplasia at the stages of proliferation, invasion and angiogenesis.
TumCI↓,
angioG↓,
*toxicity↓, The results showed that administration of emodin at the doses of 20, 40, and 80 mg/kg for 12 weeks is safe and did not cause any pathophysiological disorders in major organs in mammals.
IFN-γ↑, more interferon gamma (IFN-γ), interleukin (IL)-12 and reactive oxygen species (ROS) and less IL-6, tumor necrosis factor alpha (TNF-α) and transforming growth factor beta1 (TGF-β1) in he alveolar cavity in the emodin group than those in the control
IL12↑,
ROS↑, In vitro, emodin at the dose of 20 μM had no effect on cell viability in HL-60N1, but increased ROS and decreased autophagy, and thus induced apoptosis in HL-60N2
TNF-α↓,
TNF-α↓,
TGF-β↓,
MAPK↓, Antitumor properties of emodin are associated with inhibiting the activity of tyrosine kinases, such as mitogen-activated protein kinase (MAPK), protein kinase C (PKC), factor kappa-light-chain-enhancer of activated B cells (NF-κB)
PKCδ↓,
NF-kB↓,
HER2/EBBR2↓, emodin suppresses the activity of HER-2/neu tyrosine kinase [55]; whereas, in colon cancer cells, emodin inhibits phosphorylation of vascular endothelial growth factor (VEGF)
VEGF↓,
DNAdam↑, Another antiproliferative mechanism of emodin activity involves induction of DNA damage by the ROS, whose concentration is considerably increased in the cells treated with this anthraquinone.
Necroptosis↑, emodin induces necroptosis in the cells of renal cancer (RCC), which is resistant to conventional cancer therapy, such as chemotherapy or radiotherapy.
Glycolysis↓, and also inhibits glycolysis by downregulation of GLUT1 through ROS-mediated inactivation of the phosphoinositide 3-kinases (PI3K)/AKT signaling pathway.
GLUT1↓,
PI3K↓,
Akt↓,
Casp9↑, increasing active caspase-9, active caspase-3, and bcl-2-like protein 4 (Bax) levels and downregulating Bcl-2.
Casp3↑,
BAX↑,
Bcl-2↓,
eff↑, Li et al. [61] revealed that a bifunctional molecule of β-dihydro-artemisinin-emodin has high antiproliferative activity (suppressing Ki-67 expression),
MMP2↓, Emodin effectively inhibits the expression of the angiogenic-related NF-kB factor, as well as its regulatory factors, including VEGF, MMP-2, MMP-9.
MMP9↓,
eff↑, Combinatorial therapy with emodin and thymoquinone was also efficient in attenuating migration of MCF-7 breast cancer cells, inducing apoptosis, inhibiting cell proliferation, while enhancing cytotoxicity
ChemoSen↑, For example, combination therapy using emodin and doxorubicin sensitize breast cancer cells to doxorubicin by inhibition of proliferation in the DNA damage pathway
P-gp↓, It was demonstrated that emodin downregulated Pgp expression, and enhanced cisplatin-induced apoptosis and DNA damage in the cancer cells
SREBP2↓, suppressing the cholesterol biosynthesis (inhibition the activity of SREBP-2 protein) and inhibiting the expression of the AKT.
eff↑, emodin combined with berberine significantly inhibited the activity of salt-inducible kinases 3 (SIK3), belonging to the AMPK-related kinases, which elevated expressions in breast cancer cells contributing to tumorigenesis.
*other↝, emodin has therapeutic potential for the treatment of various kinds of inflammation, such as pancreatitis, asthma, arthritis, atherosclerosis, myocarditis, glomerulonephritis and Alzheimer’s disease.
*COX2↓, Therapeutic properties of emodin in the treatment of joint inflammation are also associated with inhibition of expression of VEGF, cyclooxygenase 2 (COX-2), hypoxia-inducible factor 1 (HIF-1)α and histone deacetylase (HDAC).
*Hif1a↓,
*HDAC↓,
*tau↓, Emodin effectively prevents abnormal aggregation of tau proteins in PHFs
*PKCδ↑, emodin improved cognitive functions by activating the protein kinase C signaling pathway (PKC), attenuating oxidative stress and inflammatory response in mice with Alzheimer’s disease.
*ROS↓,
*Inflam↓,
AntiAg?,


Showing Research Papers: 1 to 6 of 6

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 6

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

Ferroptosis↑, 1,   GPx4↓, 1,   GSH↓, 1,   HO-1↑, 1,   Iron↑, 1,   lipid-P↑, 1,   MDA↑, 1,   NADH↓, 1,   NRF2↑, 2,   OXPHOS↓, 1,   ROS↑, 2,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↓, 1,   ETC↓, 1,   p‑MEK↓, 1,   MMP↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

AMPK↑, 2,   FASN↓, 1,   G6PD↓, 1,   GLS↓, 1,   GlucoseCon↓, 1,   Glycolysis↓, 2,   HK2↓, 1,   HMG-CoA↓, 1,   lactateProd↑, 1,   LDHA↓, 1,   PDK1↓, 1,   PKM2↓, 1,   SCD1↓, 1,   SREBP2↓, 5,   SREBP2↑, 1,   Warburg↓, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 2,   Apoptosis↑, 2,   BAX↑, 1,   Bcl-2↓, 1,   Casp↑, 1,   Casp3↑, 1,   Casp9↑, 1,   Ferroptosis↑, 1,   MAPK↓, 1,   MCT1↓, 1,   Necroptosis↑, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

HER2/EBBR2↓, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

Beclin-1↓, 1,  

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↑, 1,   DNMTs↓, 1,   P53↑, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

p‑ERK↓, 1,   HDAC↓, 1,   HMGCR↓, 1,   HMGCR⇅, 1,   mTOR↓, 1,   PI3K↓, 1,   STAT3↓, 1,   Wnt↓, 1,  

Migration(tgid=13) ⓘ

AntiAg?, 1,   AntiAg↑, 1,   AP-1↓, 1,   MMP2↓, 1,   MMP9↓, 1,   MMPs↓, 1,   PKCδ↓, 1,   TGF-β↓, 1,   TumCI↓, 2,   TumCP↓, 2,   TumMeta↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 1,   Hif1a↓, 1,   VEGF↓, 2,  

Barriers & Transport(tgid=15) ⓘ

GLUT1↓, 2,   P-gp↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2↓, 1,   IFN-γ↑, 1,   IL12↑, 1,   Imm↑, 1,   NF-kB↓, 2,   NK cell↑, 1,   TNF-α↓, 2,  

Drug Metabolism & Resistance(tgid=21) ⓘ

ChemoSen↑, 3,   eff↑, 5,  

Clinical Biomarkers(tgid=22) ⓘ

GutMicro↑, 1,   HER2/EBBR2↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1,  
Total Targets: 85

Pathway results for Effect on Normal Cells:


NA, unassigned(tgid=0) ⓘ

diuretic↑, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

MDA↓, 1,   ROS↓, 2,   SOD↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

SIRT1↑, 1,   SREBP2↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

other↝, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

FOXO1↑, 1,   HDAC↓, 1,  

Migration(tgid=13) ⓘ

PKCδ↑, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

Hif1a↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2↓, 1,   Inflam↓, 3,  

Synaptic & Neurotransmission(tgid=18) ⓘ

tau↓, 1,  

Functional Outcomes(tgid=23) ⓘ

toxicity↓, 1,  

Infection & Microbiome(tgid=24) ⓘ

Bacteria↓, 1,  
Total Targets: 16

Scientific Paper Hit Count for: SREBP2, Sterol Regulatory Element-Binding Protein 2
2 Atorvastatin
2 Dipyridamole
1 Apigenin (mainly Parsley)
1 Luteolin
1 Curcumin
1 EGCG (Epigallocatechin Gallate)
1 Emodin
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#:1132  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

 

Home Page