E2Fs Cancer Research Results

E2Fs, E2F family of transcription factors: Click to Expand ⟱
Source: HalifaxProj(inactivate)
Type:
E2Fs have been classified as transcriptional activators (E2F1-3) or transcriptional repressors (E2F4-8), and are thus predicted to play a dual role in human cancers.
Activators: E2F1,2,3a,3b
Repressors: E2F4,5,6,7a,7b,8
As a tumor suppressor and oncogene, the transcription factor E2F1 is a downstream regulator of the Rb pathway.
The role of E2Fs in CSCs is widely regarded as an activator gene. Up-regulation of E2Fs is reported to be involved in proliferation promotion (21), maintenance and acquisition of self-renewal (22, 23), invasion and metastatic progression (24) and resistance to chemotherapy and radiotherapy (25) in many CSCs.
Scientific Papers found: Click to Expand⟱
1552- Api,    Apigenin inhibits the growth of colorectal cancer through down-regulation of E2F1/3 by miRNA-215-5p
- in-vitro, CRC, HCT116
Apoptosis↑,
TumCP↓,
miR-215-5p↑, miRNA-215-5p showed markedly increased
TumCCA↑, cell cycle arrest at G0/G1 phase induced by API
E2Fs↓, down-regulation of E2F1/3 by miRNA-215-5p

3391- ART/DHA,    Antitumor Activity of Artemisinin and Its Derivatives: From a Well-Known Antimalarial Agent to a Potential Anticancer Drug
- Review, Var, NA
TumCP↓, inhibiting cancer proliferation, metastasis, and angiogenesis.
TumMeta↓,
angioG↓,
TumVol↓, reduces tumor volume and progression
BioAv↓, artemisinin has low solubility in water or oil, poor bioavailability, and a short half-life in vivo (~2.5 h)
Half-Life↓,
BioAv↑, semisynthetic derivatives of artemisinin such as artesunate, arteeter, artemether, and artemisone have been effectively used as antimalarials with good clinical efficacy and tolerability
eff↑, preloading of cancer cells with iron or iron-saturated holotransferrin (diferric transferrin) triggers artemisinin cytotoxicity
eff↓, Similarly, treatment with desferroxamine (DFO), an iron chelator, renders compounds inactive
ROS↑, ROS generation may contribute with the selective action of artemisinin on cancer cells.
selectivity↑, Tumor cells have enhanced vulnerability to ROS damage as they exhibit lower expression of antioxidant enzymes such as superoxide dismutase, catalase, and gluthatione peroxidase compared to that of normal cells
TumCCA↑, G2/M, decreased survivin
survivin↓,
BAX↑, Increased Bax, activation of caspase 3,8,9 Decreased Bc12, Cdc25B, cyclin B1, NF-κB
Casp3↓,
Casp8↑,
Casp9↑,
CDC25↓,
CycB/CCNB1↓,
NF-kB↓,
cycD1/CCND1↓, decreased cyclin D, E, CDK2-4, E2F1 Increased Cip 1/p21, Kip 1/p27
cycE/CCNE↓,
E2Fs↓,
P21↑,
p27↑,
ADP:ATP↑, Increased poly ADP-ribose polymerase Decreased MDM2
MDM2↓,
VEGF↓, Decreased VEGF
IL8↓, Decreased NF-κB DNA binding [74, 76] IL-8, COX2, MMP9
COX2↓,
MMP9↓,
ER Stress↓, ER stress, degradation of c-MYC
cMyc↓,
GRP78/BiP↑, Increased GRP78
DNAdam↑, DNA damage
AP-1↓, Decreased NF-κB, AP-1, Decreased activation of MMP2, MMP9, Decreased PKC α/Raf/ERK and JNK
MMP2↓,
PKCδ↓,
Raf↓,
ERK↓,
JNK↓,
PCNA↓, G2, decreased PCNA, cyclin B1, D1, E1 [82] CDK2-4, E2F1, DNA-PK, DNA-topo1, JNK VEGF
CDK2↓,
CDK4↓,
TOP2↓, Inhibition of topoisomerase II a
uPA↓, Decreased MMP2, transactivation of AP-1 [56, 88] NF-κB uPA promoter [88] MMP7
MMP7↓,
TIMP2↑, Increased TIMP2, Cdc42, E cadherin
Cdc42↑,
E-cadherin↑,

1293- Ins,    Inositol Hexaphosphate Inhibits Growth and Induces G1 Arrest and Apoptotic Death of Androgen-Dependent Human Prostate Carcinoma LNCaP Cells
- vitro+vivo, Pca, LNCaP
TumCG↓,
TumCCA↑, increase in G1 cell population
P21↑,
CDK4↓,
cycD1/CCND1↓,
RB1↑,
E2Fs↓,

222- MFrot,  MF,    LF-MF inhibits iron metabolism and suppresses lung cancer through activation of P53-miR-34a-E2F1/E2F3 pathway
- in-vitro, Lung, A549
TumCG↓,
OS↑,
miR-34a↑, enhanced miR-34a transcription
E2Fs↓, E2F1/E2F3
P53↑,
TfR1/CD71↓, TfR1 protein levels
Ferritin↓, inhibits iron metabolism

5253- NCL,    Niclosamide: Beyond an antihelminthic drug
- Review, Var, NA
TumCP↓, Niclosamide was found to inhibit adrenocortical carcinoma cellular proliferation, which was associated with apoptosis, reduction of epithelial-to-mesenchymal transition and β-catenin levels.
Apoptosis↑,
EMT↓,
β-catenin/ZEB1↓,
TumCG↓, Oral administration of niclosamide led to tumor growth inhibition with no observed toxicity.
toxicity↓,
Wnt↓, Lu et al. reported that niclosamide inhibits Wnt/β-catenin signaling by promoting Wnt co-receptor LRP6 degradation in breast cancer cells [11].
LRP6↓,
eff↑, niclosamide acts synergistically with a monoclonal antibody that specifically activates TRAIL death receptor 5 to inhibit tumor growth of basal-like breast cancers [12].
DR5↑,
mTORC1↓,
pH↓, Niclosamide lowered the cytoplasmic pH and may indirectly lead to inhibition of mTORC1 signaling [13]
CSCs↓, Niclosamide also was found to prevent the conversion of non-breast cancer stem cells into cancer stem cells
IL6↓, This mechanism is associated with inhibition of the IL6-JAK1-STAT3 signal transduction pathway
JAK1↓,
STAT3↓, Ren et al. identified niclosamide as a potent STAT3 inhibitor able to suppress STAT3 transcriptional activity
ChemoSen↑, niclosamide alone or in combination with cisplatin represses the growth of xenografts of cisplatin-resistant triple-negative breast cancer cells.
TumCG↓, Niclosamide inhibited growth of colon cancer cells from human patients both in vitro and in vivo, regardless of mutations in APC [24].
tumCV↓, niclosamide selectively inhibited glioblastoma cell viability [29]. Detailed mechanism studies revealed that niclosamide suppressed the Wnt, Notch, mTOR, and NF-κB signaling pathways.
NOTCH↓,
NF-kB↓,
EGFR↓, Li et al. reported that inhibition of EGFR by erlotinib, an FDA-approved therapeutic agent, led to activation of STAT3 signaling in head and neck cancer cells
ROS↑, niclosamide inhibits TNF-α-induced NF-κB–dependent reporter activity and increased the levels of reactive oxygen species (ROS) in AML cells.
RadioS↑, niclosamide enhanced radiosensitivity of the non-small cell lung cancer cell line H1299.
cFos↓, inhibit osteosarcoma cell proliferation, migration, and survival. This inhibitory effect is associated with decreased expression of c-Fos, c-Jun. E2F1, and c-Myc.
cJun↓,
E2Fs↓,
cMyc↓,
Half-Life↓, Niclosamide exhibits a short half-life (6.0 ± 0.8 h). Niclosamide was rapidly absorbed with a Tmax of less than 30 min. The Cmax is 354 ± 152 ng/mL.
BioAv↝, AUC and bioavailability were 429 ± 100 and 10%, respectively. In order to make more effective use of niclosamide, additional work needs to be done to improve its solubility, absorption and systemic bioavailability.

5254- NCL,    The magic bullet: Niclosamide
- Review, Var, NA
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

58- QC,  doxoR,    Quercetin induces cell cycle arrest and apoptosis in CD133+ cancer stem cells of human colorectal HT29 cancer cell line and enhances anticancer effects of doxorubicin
- in-vitro, CRC, HT-29 - in-vitro, NA, CD133+
Bcl-2↓,
TumCCA↑, Quercetin induces cell cycle arrest and apoptosis in CD133+ cancer stem cells of human colorectal HT29 cancer cell line and enhances anticancer effects of doxorubicin
CD133↓,
CSCs↓,
ChemoSen↑, adding quercetin to Dox chemotherapy is an effective strategy for treatment of both CSCs and bulk tumor cells.
CycB/CCNB1↑, Quer induces G2/M phase accumulation due to enhanced level of the cyclin B and decreased level of the cyclin E, cyclin D, E2F1, and E2F2
cycE/CCNE↓,
cycD1/CCND1↓,
E2Fs↓,

40- QC,    Quercetin arrests G2/M phase and induces caspase-dependent cell death in U937 cells
- in-vitro, lymphoma, U937
cycD1/CCND1↓, dramatic changes in the level of cyclin B, cyclin D, and cyclin E
cycE/CCNE↓,
E2Fs↓,
CycB/CCNB1↑, The G2/M phase accumulation was accompanied by an increase in the level of the cyclin B.
Casp↑, These data clearly indicate that quercetin-induced apoptosis is associated with caspase activation
Apoptosis↑,
TumCCA↑, We report here that quercetin induces anti-proliferation and arrests G2/M phase in U937 cells.
TumCP↓,

100- QC,    Inhibition of Prostate Cancer Cell Colony Formation by the Flavonoid Quercetin Correlates with Modulation of Specific Regulatory Genes
- in-vitro, Pca, PC3 - in-vitro, Pca, DU145 - in-vitro, Pca, LNCaP
cycD1/CCND1↓, CCND1, CCND2, CCND3
cycE/CCNE↓, CCNE1, CCNE2
CDK2↓,
CDK4/6↓, CDK4, CDK8
E2Fs↓, E2F2, E2F3
PCNA↓,
cDC2↓,
PTEN↑,
MSH2↑,
P21↑,
EP300↑, p300
BRCA1↑,
NF2↑,
TSC1↑,
TGFβR1↑, TGFβR2
P53↑,
RB1↑, Rb
AKT1↓,
cMyc↓,
CDC7↓,
cycF↓, CCNF
CDC16↓,
CUL4B↑, CUL4B, a member of the cullin gene family that is also known to be involved in control of the cell cycle, was significantly up-regulated by quercetin.
CBP↑,
TSC2↑,
HER2/EBBR2↓, erb-2
BCR↓,
TumCCA↑, quercetin significantly inhibited the expression of specific oncogenes and genes controlling G1, S, G2, and M phases of the cell cycle.
chemoPv↑, Our results correlate with those of nutritional studies that support the roles of dietary bioflavonoids as cancer chemopreventive agents.

3323- SIL,    Anticancer therapeutic potential of silibinin: current trends, scope and relevance
- Review, Var, NA
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↓,

3427- TQ,    Chemopreventive and Anticancer Effects of Thymoquinone: Cellular and Molecular Targets
ROS⇅, It appears that the cellular and/or physiological context(s) determines whether TQ acts as a pro-oxidant or an anti-ox- idant in vivo
Fas↑, Figure 2, cell death
DR5↑,
TRAIL↑,
Casp3↑,
Casp8↑,
Casp9↑,
P53↑,
mTOR↓,
Bcl-2↓,
BID↓,
CXCR4↓,
JNK↑,
p38↑,
MAPK↑,
LC3II↑,
ATG7↑,
Beclin-1↑,
AMPK↑,
PPARγ↑, cell survival
eIF2α↓,
P70S6K↓,
VEGF↓,
ERK↓,
NF-kB↓,
XIAP↓,
survivin↓,
p65↓,
DLC1↑, epigenetic
FOXO↑,
TET2↑,
CYP1B1↑,
UHRF1↓,
DNMT1↓,
HDAC1↓,
IL2↑, inflammation
IL1↓,
IL6↓,
IL10↓,
IL12↓,
TNF-α↓,
iNOS↓,
COX2↓,
5LO↓,
AP-1↓,
PI3K↓, invastion
Akt↓,
cMET↓,
VEGFR2↓,
CXCL1↓,
ITGA5↓,
Wnt↓,
β-catenin/ZEB1↓,
GSK‐3β↓,
Myc↓,
cycD1/CCND1↓,
N-cadherin↓,
Snail↓,
Slug↓,
Vim↓,
Twist↓,
Zeb1↓,
MMP2↓,
MMP7↓,
MMP9↓,
JAK2↓, cell proliferiation
STAT3↓,
NOTCH↓,
cycA1/CCNA1↓,
CDK2↓,
CDK4↓,
CDK6↓,
CDC2↓,
CDC25↓,
Mcl-1↓,
E2Fs↓,
p16↑,
p27↑,
P21↑,
ChemoSen↑, Such chemo-potentiating effects of TQ in different cancer cells have been observed with 5-fluorouracil in gastric cancer and colorectal cancer models


Showing Research Papers: 1 to 11 of 11

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 11

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   ROS↑, 2,   ROS⇅, 1,  

Metal & Cofactor Biology ⓘ

Ferritin↓, 1,   TfR1/CD71↓, 1,  

Mitochondria & Bioenergetics ⓘ

ADP:ATP↑, 1,   BCR↓, 1,   CDC16↓, 1,   CDC2↓, 1,   CDC25↓, 2,   ETC↑, 1,   Raf↓, 1,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

AKT1↓, 1,   AMPK↑, 2,   ATG7↑, 1,   cMyc↓, 3,   NADH:NAD↓, 1,   PPARγ↑, 1,   TCA↑, 1,   Warburg↓, 1,  

Cell Death ⓘ

Akt↓, 1,   p‑Akt↓, 1,   Apoptosis↑, 3,   BAX↑, 1,   Bcl-2↓, 2,   BID↓, 1,   Casp↑, 1,   Casp3↓, 1,   Casp3↑, 1,   Casp8↑, 2,   Casp9↑, 2,   CBP↑, 1,   DR5↑, 2,   Fas↑, 1,   iNOS↓, 1,   JNK↓, 1,   JNK↑, 1,   MAPK↑, 1,   Mcl-1↓, 1,   MDM2↓, 1,   Myc↓, 2,   p27↑, 2,   p38↑, 1,   survivin↓, 2,   TRAIL↑, 1,   TumCD↑, 1,  

Kinase & Signal Transduction ⓘ

CDC7↓, 1,   HER2/EBBR2↓, 1,   TSC2↑, 1,  

Transcription & Epigenetics ⓘ

cJun↓, 1,   tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

eIF2α↓, 1,   ER Stress↓, 1,   GRP78/BiP↑, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1,   LC3II↑, 1,  

DNA Damage & Repair ⓘ

BRCA1↑, 1,   CUL4B↑, 1,   CYP1B1↑, 1,   DNAdam↑, 1,   DNMT1↓, 1,   p16↑, 1,   P53↑, 4,   PCNA↓, 2,   UHRF1↓, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 4,   CDK4↓, 4,   cycA1/CCNA1↓, 1,   CycB/CCNB1↓, 1,   CycB/CCNB1↑, 2,   cycD1/CCND1↓, 7,   cycE/CCNE↓, 4,   cycF↓, 1,   E2Fs↓, 11,   P21↑, 4,   RB1↑, 2,   TumCCA↑, 7,  

Proliferation, Differentiation & Cell State ⓘ

CD133↓, 1,   cDC2↓, 1,   cFos↓, 1,   cMET↓, 1,   CSCs↓, 2,   Diff↑, 1,   EMT↓, 1,   EP300↑, 1,   ERK↓, 2,   FOXO↑, 1,   GSK‐3β↓, 1,   HDAC1↓, 1,   LRP6↓, 1,   miR-34a↑, 1,   mTOR↓, 2,   mTORC1↓, 1,   NF2↑, 1,   NOTCH↓, 3,   P70S6K↓, 1,   PI3K↓, 2,   PTEN↑, 1,   RAS↓, 1,   STAT3↓, 3,   p‑STAT3↓, 1,   TOP2↓, 1,   TumCG↓, 4,   Wnt↓, 3,  

Migration ⓘ

5LO↓, 1,   AP-1↓, 2,   Cdc42↑, 1,   CDK4/6↓, 1,   DLC1↑, 1,   E-cadherin↑, 1,   ITGA5↓, 1,   KRAS↓, 1,   miR-215-5p↑, 1,   MMP2↓, 3,   MMP7↓, 2,   MMP9↓, 2,   MSH2↑, 1,   N-cadherin↓, 1,   PKCδ↓, 1,   Slug↓, 2,   Snail↓, 2,   TIMP2↑, 1,   TSC1↑, 1,   TumCP↓, 5,   TumMeta↓, 2,   Twist↓, 1,   uPA↓, 1,   Vim↓, 1,   Zeb1↓, 2,   α-SMA↓, 1,   β-catenin/ZEB1↓, 3,  

Angiogenesis & Vasculature ⓘ

angioG↓, 2,   EGFR↓, 1,   p‑EGFR↓, 1,   HIF-1↓, 2,   VEGF↓, 3,   VEGFR2↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 3,   CXCL1↓, 1,   CXCR4↓, 1,   IL1↓, 1,   IL10↓, 1,   IL12↓, 1,   IL2↑, 1,   IL6↓, 3,   IL8↓, 1,   Inflam↓, 1,   JAK1↓, 1,   JAK2↓, 2,   NF-kB↓, 4,   p65↓, 1,   PD-1↓, 1,   PD-L1↓, 2,   TNF-α↓, 1,  

Cellular Microenvironment ⓘ

pH↓, 1,  

Protein Aggregation ⓘ

PP2A↑, 1,  

Hormonal & Nuclear Receptors ⓘ

CDK6↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 2,   BioAv↝, 2,   ChemoSen↑, 4,   Dose↑, 1,   Dose↝, 1,   eff↓, 1,   eff↑, 3,   Half-Life↓, 2,   RadioS↑, 2,   selectivity↑, 1,   TET2↑, 1,  

Clinical Biomarkers ⓘ

BRCA1↑, 1,   EGFR↓, 1,   p‑EGFR↓, 1,   Ferritin↓, 1,   HER2/EBBR2↓, 1,   IL6↓, 3,   KRAS↓, 1,   Myc↓, 2,   PD-L1↓, 2,  

Functional Outcomes ⓘ

chemoPv↑, 1,   OS↑, 1,   TGFβR1↑, 1,   toxicity↓, 2,   TumVol↓, 1,  
Total Targets: 184

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: E2Fs, E2F family of transcription factors
3 Quercetin
2 Niclosamide (Niclocide)
1 Apigenin (mainly Parsley)
1 Artemisinin
1 Inositol
1 Magnetic Field Rotating
1 Magnetic Fields
1 doxorubicin
1 Silymarin (Milk Thistle) silibinin
1 Thymoquinone
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#:90  State#:%  Dir#:1
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