STAT3 Cancer Research Results

STAT3, Signal transducer and activator of transcription 3: Click to Expand ⟱

Source:

Type: Oncogene

Stat3 (Signal Transducer and Activator of Transcription 3) is a transcription factor that plays a crucial role in various cellular processes, including cell growth, survival, differentiation, and immune response.
Stat3 is frequently found to be constitutively activated in many types of cancers, including breast, prostate, lung, and head and neck cancers. (associated with poor prognosis and reduced survival.)

-STAT3 is typically activated by cytokines (such as IL-6) and growth factors binding to their respective receptors.
-Activated STAT3 upregulates the expression of genes that promote cell cycle progression (e.g., cyclin D1) and anti-apoptotic proteins (e.g., Bcl-2, Bcl-xL).

Scientific Papers found: Click to Expand⟱

2676-

BBR,

Berberine protects rat heart from ischemia/reperfusion injury via activating JAK2/STAT3 signaling and attenuating endoplasmic reticulum stress

in-vivo,

Nor,

Male rats were treated with BBR (200 mg·kg−1·d−1, ig) for 2 weeks, and then subjected to MI/R surgery.

in-vivo,

CardioV,

*cardioP↑, Pretreatment with BBR significantly reduced MI/R-induced myocardial infarct size, improved cardiac function, and suppressed myocardial apoptosis and oxidative damage.
*ROS↓,
*ER Stress↓, pretreatment with BBR suppressed MI/R-induced ER stress
*p‑PERK↓, evidenced by down-regulating the phosphorylation levels of myocardial PERK and eIF2α and the expression of ATF4 and CHOP in heart tissues.
*p‑eIF2α↓,
*ATF4↓,
CHOP/DDIT3↓,
*JAK2↑, Pretreatment with BBR also activated the JAK2/STAT3 signaling pathway in heart tissues
*STAT3↑,
*UPR↓, Therefore, reducing excessive UPR, also referred to as ER stress, is of great importance in ameliorating MI/R injury.

6499-

BCP,

JAK1/STAT3 regulatory effect of β-caryophyllene on MG-63 osteosarcoma cells via ROS-induced apoptotic mitochondrial pathway by DNA fragmentation

in-vitro,

OS,

MG63

ROS↑, BCP induced reactive oxygen species (ROS) generation at 20 µM concentration in MG-63 cells.
Apoptosis↑, The same dose was also shown to exhibit proapoptotic and antiproliferative effects in bone cancer cells MG-63.
TumCP↓,
BAX↑, BCP prompted mitochondrial apoptosis via upregulation of Bax and caspase-3 and downregulation of Bcl-2 as well as prompted mitochondrial membrane potential.
Casp3↑,
Bcl-2↓,
MMP↓, The turn down in mitochondrial membrane potential was discover in concentrations (15 and 20 μM/mL) of BCP compared as control cancer cells.
DNAdam↑, DNA damage were increased in BCP (15 and 20 μM/mL) treated MG‐63 cells in a dose dependent manner.
TNF-α↓, Our results showed downregulation of all the inflammatory genes analyzed (TNF‐α, COX‐2, NF‐κB, and IL‐6) indicating an anti‐inflammatory property of BCP
COX2/PTGS2↓,
NF-kB↓,
IL6↓,
Inflam↓,
JAK1↑, increased levels of both JAK1 and STAT3 in MG‐63 cells upon treatment with BCP (15 and 20 μM/mL)
STAT3↑,

2742-

BetA,

Betulinic acid impairs metastasis and reduces immunosuppressive cells in breast cancer models

in-vitro,

BC,

MDA-MB-231

in-vivo,

BC,

4T1

intraperitoneal administration of 10 mg/kg/day BA

in-vitro,

BC,

MCF7

tumCV↓, BA decreased the viability of three breast cancer cell lines and markedly impaired cell migration and invasion
TumCMig↓,
TumCI↓,
STAT3↑, BA could inhibit the activation of stat3 and FAK which resulted in a reduction of matrix metalloproteinases (MMPs)
FAK↓,
MMPs↓,
MMP2↓, BA treatment decreased the expression of MMP-2 and MMP-9 while increased the expression of TIMP-2 in 4T1 and MDA-MB-231 cells.
MMP9↓,
TIMP2↑,

2773-

Bos,

Targeted inhibition of tumor proliferation, survival, and metastasis by pentacyclic triterpenoids: Potential role in prevention and therapy of cancer

Review,

Var,

Inflam↓, BA has been shown to be effective against chronic inflammation-driven diseases such as adjuvant or bovine serum albumin-induced arthritis, osteoarthritis, Crohnâs disease, ulcerative colitis, and ileitis, and galactosamine/endotoxin-induced hepa
TumCCA↑, BA induced apoptosis was mediated by cell cycle arrest in the G1 phase and by activating caspases 3, 8 and 9 in HT-29 cells
Casp3↑,
Casp8↑,
Casp9↑,
STAT3↑, BA inhibited the growth of multiple myeloma cells by suppression of STAT3 pathway and by activation of protein tyrosine phosphatase SHP1
SHP1↓,
NF-kB↓, BA down regulated the expression of NF-kB, cyclin D1, COX2, Ki-67, CD-31 and IAPs in the tumor tissue.
cycD1/CCND1↓,
COX2/PTGS2↓,
Ki-67↓,
CD31/PECAM-1↓,
IAP1↓,
MMPs↓, AKBA induced cell cycle arrest was mediated by down-regulating the expression of cyclinD1, suppresses MMP activity, and also induced apoptosis by suppressing Bcl-2, and Bcl-xL expression
Bcl-2↓,
Bcl-xL↓,

5204-

CAP,

Low-concentration capsaicin promotes colorectal cancer metastasis by triggering ROS production and modulating Akt/mTOR and STAT-3 pathways

in-vitro,

Colon,

SW480

in-vitro,

Colon,

CT26

TumCP↓, high-concentration of capsaicin (≥ 200 µM for SW480 and CT-26 cell lines; ≥ 25 µM for HCT116 cell line) inhibited CRC cell proliferation in a dose-dependent manner
TumCMig↑, low-concentration of capsaicin (100 µM for SW480 and CT-26 cell lines; 12.5 µM for HCT116 cell line) enhanced both migratory and invasive capability of these cells
TumCI↑,
EMT↑, 100 µM capsaicin induced epithelial-to-mesenchymal (EMT), up-regulated expression of MMP-2 and MMP-9, and activated Akt/mTOR and STAT-3 pathways in SW480 cells.
MMP2↓,
MMP9↑,
STAT3↑,
TumMeta↑, capsaicin-induced metastasis of CRC cells was mediated by modulating reactive oxygen species (ROS) production.
ROS↑,

5201-

CAP,

Inhibiting ROS-STAT3-dependent autophagy enhanced capsaicin-induced apoptosis in human hepatocellular carcinoma cells

NA,

HCC,

HepG2

50, 100 and 200μmol/L) for 6, 12, and 24 h.

AntiCan↓, Capsaicin, which is the pungent ingredient of red hot chili peppers, has been reported to possess anticancer activity, including that against hepatocellular carcinoma.
Apoptosis↑, Capsaicin can induce apoptosis in HepG2 cells.
cl‑PARP↑, The expression levels of CL-PARP and Bcl-2 were significantly increased.
Bcl-2↑,
TumAuto↑, capsaicin can trigger autophagy in HepG2 cells.
LC3II↑, Capsaicin increased LC3-II and beclin-1 expression and GFP-LC3-positive autophagosomes.
eff↑, Pharmacological or genetic inhibition of autophagy further sensitized HepG2 cells to capsaicin-induced apoptosis.
STAT3↑, capsaicin upregulated the Stat3 activity which contributed to autophagy
ROS↑, capsaicin triggered reactive oxygen species (ROS) generation in hepatoma cells
eff↓, and that the levels of ROS decreased with N-acetyl-cysteine (NAC), a ROS scavenger.

2018-

CAP,

MF,

Capsaicin: Effects on the Pathogenesis of Hepatocellular Carcinoma

Review,

HCC,

TRPV1↑, Capsaicin is an agonist for transient receptor potential cation channel subfamily V member 1 (TRPV1)
eff↑, It is noteworthy that capsaicin binding to the TRPV1 receptor may be increased using a static magnetic field (SMF), thus enhancing the anti-cancer effect of capsaicin on HepG2 (human hepatoblastoma cell line) cells through caspase-3 apoptosis
Akt↓, capsaicin can regulate autophagy by inhibiting the Akt/mTOR
mTOR↓,
p‑STAT3↑, Capsaicin can upregulate the activity of the signal transducer and activator of transcription 3 (p-STAT3)
MMP2↑, increase of the expression of MMP-2
ER Stress↑, capsaicin may induce apoptosis through endoplasmic reticulum (ER) stress
Ca+2↑, and the subsequent ER release of Ca2+
ROS↑, Capsaicin-induced ROS generation
selectivity↑, On the other hand, an excess of capsaicin is cytotoxic on HepG2 cells, and normal hepatocytes to a smaller extent, by collapse of the mitochondrial membrane potential with ROS formation
MMP↓,
eff↑, combination of capsaicin and sorafenib demonstrated significant anticarcinogenic properties on LM3 HCC cells, restricting tumor cell growth

2780-

CHr,

Anti-cancer Activity of Chrysin in Cancer Therapy: a Systematic Review

Review,

Var,

*antiOx↑, antioxidant (13), anti-inflammatory (14), antibacterial (15), anti-hypertensive (16), anti-allergic (17), vasodilator (18),
Inflam↓,
*hepatoP↑, anti-diabetic (19), anti-anxiety (10), anti-viral (20), anti-estrogen (21), liver protective (22), anti-aging (23), anti-seizure (24), and anti-cancer effects (25)
AntiCan↑,
Cyt‑c↑, (1) facilitating the release of cytochrome C from the mitochondria,
Casp3↑, (2) activating caspase-3 and inhibiting the activity of the XIAP molecule,
XIAP↓,
p‑Akt↓, (3) reducing AKT phosphorylation and triggering the PI3K pathway and induction of apoptosis
PI3K↑,
Apoptosis↑,
COX2/PTGS2↓, chrysin interacts weakly with COX-1 binding site whereas displayed a remarkable interaction with COX-2.
FAK↓, ESCC cells: resultant blockage of the FAK/AKT signaling pathways
AMPK↑, A549: activation of AMPK by chrysin contributes to Akt suppression
STAT3↑, 4T1cell: inhibited STAT3 activation
MMP↓, Chrysin induces apoptosis through the intrinsic mitochondrial pathway that disrupts mitochondrial membrane potential (MMP) and increases DNA fragmentation.
DNAdam↑,
BAX↑, produces pro-apoptotic proteins, including Bax and Bak, and activates caspase-9 and caspase-3 in various cancer cells
Bak↑,
Casp9↑,
p38↑, chrysin can inhibit tumor growth by activating P38 MAPK and stopping the cell cycle
MAPK↑,
TumCCA↑,
ChemoSen↑, beneficial in inhibiting chemotherapy resistance of cancer cells
HDAC8↓, chrysin suppresses tumorigenesis by inhibiting histone deacetylase 8 (HDAC8)
Wnt↓, chrysin can attenuate Wnt and NF-κB signaling pathways
NF-kB↓,
angioG↓, chrysin can inhibit angiogenesis and inducing apoptosis in HTh7 cells, 4T1 mice, and MDA-MB-231 cells
BioAv↓, low bioavailability of flavonoids such as chrysin

2784-

CHr,

Chrysin targets aberrant molecular signatures and pathways in carcinogenesis (Review)

Review,

Var,

Apoptosis↑, apoptosis, disrupting the cell cycle and inhibiting migration without generating toxicity or undesired side‑effects in normal cells
TumCMig↓,
*toxicity↝, toxic at higher doses and the recommended dose for chrysin is <3 g/day
ChemoSen↑, chrysin also inhibits multi‑drug resistant proteins and is effective in combination therapy
*BioAv↓, extremely low bioavailability in humans due to rapid quick metabolism, removal and restricted assimilation. The bioavailability of chrysin when taken orally has been estimated to be between 0.003 to 0.02%
Dose↝, safe and effective in various studies where volunteers have taken oral doses ranging from 300 to 625 mg without experiencing any documented effect
neuroP↑, Chrysin has been shown to exert neuroprotective effects via a variety of mechanisms, such as gamma-aminobutyric acid mimetic properties, monoamine oxidase inhibition, antioxidant, anti-inflammatory and anti-apoptotic activities
*P450↓, Chrysin inhibits cytochrome P450 2E1, alcohol dehydrogenase and xanthine oxidase at various dosages (20 and 40 mg/kg body weight) and protects Wistar rats against oxidative stress
*ROS↓,
*HDL↑, ncreased the levels of high-density lipoprotein cholesterol, glutathione S-transferase, superoxide dismutase and catalase
*GSTs↑,
*SOD↑,
*Catalase↑,
*MAPK↓, inactivate the MAPK/JNK pathway and suppress the NF-κB pathways, and at the same time upregulate the expression of PTEN, and activate the VEGF/AKT pathway
*NF-kB↓,
*PTEN↑,
*VEGF↑,
ROS↑, chrysin treatment in ovarian cancer led to the augmented generation of reactive oxygen species, a decrease in MMP and an increase in cytoplasmic Ca2+,
MMP↓,
Ca+2↑,
selectivity↑, It has been found that chrysin has no cytotoxic effect on normal cells, such as fibroblasts
PCNA↓, Chrysin likewise downregulates proliferating cell nuclear antigen (PCNA) expression in cervical carcinoma cells
Twist↓, Chrysin decreases the expression of TWIST 1 and NF-κB and thus suppresses epithelial-mesenchymal transition (EMT) in HeLa cells
EMT↓,
CDKN1C/p57↑, Chrysin administration led to the upregulation of CDKN1 at the transcript and protein leve
p‑STAT3↑, Chrysin decreased the viability of 4T1 breast cancer cells by suppressing hypoxia-induced phosphorylation of STAT3
MMP2↓, chrysin-loaded PGLA/PEG nanoparticles modulated TIMPS and MMP2 and 9, and PI3K expression in a mouse 4T1 breast tumor model
MMP9↓,
eff↑, Chrysin used alone and as an adjuvant with metformin has been found to downregulate cyclin D and hTERT expression in the breast cancer cell line
cycD1/CCND1↓,
hTERT/TERT↓,
CLDN1↓, CLDN1 and CLDN11 expression have been found to be higher in human lung squamous cell carcinoma. Treatment with chrysin treatment reduces both the mRNA and protein expression of these claudin genes
TumVol↓, Treatment with chrysin treatment (1.3 mg/kg body weight) significantly decreases tumor volume, resulting in a 52.6% increase in mouse survival
OS↑,
COX2/PTGS2↓, Chrysin restores the cellular equilibrium of cells subjected to benzopyrene by downregulating the expression of elevated proteins, such as PCNA, NF-κB and COX-2
eff↑, quercetin and chrysin together decreased the levels of pro-inflammatory molecules, such as IL-6, -1 and -10, and the levels of TNF via the NF-κB pathway.
CDK2↓, Chrysin has been shown to inhibit squamous cell carcinoma via the modulation of Rb and by decreasing the expression of CDK2 and CDK4
CDK4↓,
selectivity↑, chrysin selectively exhibits toxicity and induces the self-programed death of human uveal melanoma cells (M17 and SP6.5) without having any effect on normal cells
TumCCA↑, halting the cell cycle at the G2/M or G1/S phases
E-cadherin↑, upregulation of E-cadherin and the downregulation of cadherin
HK2↓, Chrysin decreased expression of HK-2 in mitochondria, and the interaction between HK-2 and VDAC 2 was disrupted,
HDAC↓, Chrysin, a HDAC inhibitor, caused cytotoxicity, and also inhibited migration and invasion.

6185-

Cuc,

Cucurbitacin B: A review of its pharmacology, toxicity, and pharmacokinetics

Review,

Var,

Review,

Arthritis,

Review,

AD,

*Inflam↓, results showed that CuB exhibits potent anti-inflammatory, antioxidant, antiviral, hypoglycemic, hepatoprotective, neuroprotective, and anti-cancer activities
*antiOx↑,
*hepatoP↑,
*neuroP↑,
*AntiCan↑,
*toxicity↝, Studies of its toxicity and pharmacokinetic properties showed that CuB has non-specific toxicity and low bioavailability.
*BioAv↓,
*HO-1↑, CuB can exert its anti-inflammatory effect via the induction of heme oxygenase-1 (HO-1) by the activation Nrf2 [25].
*NRF2↑,
*NLRP3↑, CuB could act as an anti-inflammatory agent to inhibit gouty arthritis in mice [28]. The mechanism of action was mainly attributed to inhibition of the formation and activation of the NOD-like receptor thermal protein domain associated protein 3 (NLR
*SOD↑, Its antioxidant activity may be indirectly realized by increasing the activities of the antioxidant enzymes total SOD and SOD-1, and thereby eliminating excessive ROS and other free radicals in cells
*SOD1↑,
*ROS↓,
*AntiAge↑, this study also confirmed that CuB could exert anti-aging effects by regulating autophagy, ROS, and aging-related genes, which suggested that CuB might be a promising anti-aging drug
*ARE↑, activating the Nrf2/ARE signaling pathway and inhibiting the STAT/NF-κB signaling pathway, and thereby exerting a protective effect on cortical neurons
*STAT↓,
*NF-kB↓,
*neuroG↑, CuB (0.1 mg/kg) could also promote neurogenesis in APP/PS1 mice and alleviate memory deficits associated with enhanced neurogenesis in mice.
*memory↑,
ROS↑, Figure 2
NLRP3↑,
CIP2A↓,
Akt↓,
STAT3↑,
VEGFR2/KDR/Flk1↓,
DNMTs↓, tudies have shown that in H1299 human lung cancer cells CuB (6, 60, 600, and 860 nM) can inhibit DNA methyltransferases (DNMTs)
MAPK↓,
YAP/TEAD↓,
PI3K↓,
Wnt↓,
NOTCH↓,
TumCCA↑,
TumCG↓, Inhibit cell growth and proliferation
TumCP↓,
FAK↑, CuB inhibited the migration, invasion, and adhesion of KKU-452 CCA cells in a dose-dependent manner by suppressing the activation of FAK and down-regulating MMP-9,
MMP9↓,
TumAuto↑, CuB ccould induce autophagy in BEL-7402 hepatocellular carcinoma cells by affecting autophagy-related proteins, such as up-regulating the expression of light chain 3 (LC3)-II
toxicity↝, Most experiments have demonstrated that CuB is moderately cytotoxic, both to human cancer cells and to normal cells
BioAv↓, When Wistar rats were given CuB orally at a dose of 8 mg/kg, the absorption degree was low and the absorption speed was slowest, which was specifically reflected in the fact that the time to peak concentration was longest (180 min, Tmax = 3 h). T
Half-Life↝, When CuB was administered intravenously at 0.1 mg/kg and orally at 1 mg/kg, the clearance rates of CuB in Wistar rats were similar, with a half-life (t1/2) of 5.08 ± 2.87 h and 5.09 ± 2.20 h, respectively [139].
BioAv↑, CuB-loaded mixed micelles with collagen peptides as a carrier, which improved the solubility of CuB and enhanced the absorption of orally administered CuB, and its relative bioavailability increased by a factor of 3.43
selectivity∅, Although CuB displays potent activity against tumor cells, its non-selective toxicity has limited its clinical applications.

6360-

DRE,

Dandelion Seed Extract Affects Tumor Progression and Enhances the Sensitivity of Cisplatin in Esophageal Squamous Cell Carcinoma

in-vitro,

ESCC,

KYSE450

in-vitro,

ESCC,

Eca109

TumCG↓, The results indicated that DSE selectively inhibited cell growth, proliferation, migration, invasion, angiogenesis and induced cell apoptosis in ESCC cells.
TumCP↓,
TumCMig↓,
TumCI↓,
angioG↓,
Apoptosis↑,
PI3K↓, decreased PI3K, Akt and pAkt proteins levels in KYSE450 and Eca109 cells administrated with DSE.
Akt↓,
p‑Akt↓,
survivin↓, application of DSE decreased the level of survivin and the ratio of Bcl-2/Bax, while increased the levels of caspase3 and caspase9.
Bax:Bcl2↑,
Casp3↑,
Casp9↑,
MMP2↓, DSE significantly decreased the levels of MMP2, MMP9 and VEGF proteins and inhibited the EMT progression in KYSE450 and Eca109 cells
MMP9↓,
VEGF↓,
EMT↓,
eff↑, DSE enhances the sensitivity of DDP to human ESCC cells via promoting DNA damage and inhibiting phosphorylation of STAT3.
DNAdam↑,
p‑STAT3↑,
ChemoSen↑, DSE may affect ESCC progression and enhance the sensitivity of cisplatin, and consequently become an effective anti-cancer option for human ESCC treatment.

6829-

EMD,

Molecular Mechanisms of Action of Emodin: As an Anti-Cardiovascular Disease Drug

*diuretic↑, diuretic, vasorelaxant, anti-bacterial, anti-viral, anti-ulcerogenic, anti-inflammatory, and anti-cancer effects.
*Bacteria↓,
*AntiViral↑,
*Inflam↓,
AntiCan↑,
*cardioP↑, timely overview of emodin related to the treatment of cardiovascular disease.
*NF-kB↓, graphic abstract Immunomoduation
*TNF-α↓,
*IL1β↓,
*NO↑,
*eNOS↑,
*PPARγ↑,
*Casp9↓, anti-apoptosis
*Casp3↓,
*GSDMD↓,
*Bcl-2↑,
*STAT3↑,
*ATP↑, anti-oxidant
*SOD↑,
*GSH↑,
*HDAC2↓, anti cardiac hypertrophy
*SIRT3↑,
ROS↑, anti-proliferative
PCNA↓,
P53↑,
cMyc↓,

6982-

Form,

Formononetin: A Review of Its Anticancer Potentials and Mechanisms

Review,

Var,

AntiTum↑, Formononetin elicits antitumorigenic properties in vitro and in vivo by modulating numerous signaling pathways to induce cell apoptosis (by intrinsic pathway involving Bax, Bcl-2, and caspase-3 proteins)
Apoptosis↑,
BAX↑,
Bcl-2↓,
Casp3↑,
TumCCA↑, cell cycle arrest (by regulating mediators like cyclin A, cyclin B1, and cyclin D1),
cycA1/CCNA1↓,
CycB/CCNB1↓,
cycD1/CCND1↓,
TumCP↓, suppress cell proliferation [by signal transducer and activator of transcription (STAT) activation, phosphatidylinositol 3-kinase/protein kinase-B (PI3K/AKT), and mitogen-activated protein kinase (MAPK) signaling pathway],
VEGF↓, inhibit cell invasion [by regulating growth factors vascular endothelial growth factor (VEGF) and Fibroblast growth factor 2 (FGF2), and matrix metalloproteinase (MMP)-2 and MMP-9 proteins].
FGF↓,
MMP2↓,
MMP9↓,
eff↑, Co-treatment with other chemotherapy drugs such as bortezomib, LY2940002, U0126, sunitinib, epirubicin, doxorubicin, temozolomide, and metformin enhances the anticancer potential of both formononetin and the respective drugs through synergistic effec
ChemoSen↑,
chemoPv↑, Compiling the evidence thus far highlights the potential of formononetin to be a promising candidate for chemoprevention and chemotherapy.
p‑Akt↓, downregulation of EphB3, p-AKT, p-P13K, p-STAT3, inhibition of cyclin D1, MMP2/9
p‑STAT3↑,
TumCMig↓, MDA-MB-231-luc and 4T1 Inhibition of cell migration and invasion, elevation of TIMP-1 and TIMP-2, and suppression of PI3K/AKT signaling
TumCI↓,
TIMP1↑,
TIMP2↑,
PI3K↓,
Akt↓,
Dose↝, formononetin is administered into the mice intraperitoneally or intragastrically, mainly at doses between 10 and 60 mg/kg for 2–3 weeks via intraperitoneal route and between 15 and 100 mg/kg for more than a month via intragastric route
TumCG↓, In general, the formononetin treatment suppresses xenograft tumor growth in terms of tumor weight and volume, and also inhibits tumor invasiveness and angiogenesis.
TumW↓,
TumVol↓,
angioG↓,
Casp3↑, After exposure to formononetin, expression levels of cleaved caspase-3 and -9 in ovarian cancer cells increased in a dose-dependent manner
Casp9↑,
cl‑PARP↑, leading to the cleavage of poly(ADP-ribose) polymerase (PARP), which results in the inability to repair damaged DNA
DNArepair↓,
MMP↓, significant loss of mitochondrial membrane potential of approximately 457% (P < 0.001) and 265% (P < 0.001) in ES2 and OV90 ovarian cancer cells was observed upon exposure to 40 µM formononetin
BAX↑, expression of Bax protein surged upon formononetin treatment, while Bcl-2 protein level decreased
Bcl-2↓,
DR5↑, formononetin displayed high affinity and steric compatibility to death receptor 5, which could be activated to mediate the TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis
ROS↑, Formononetin can also induce the apoptotic pathway via the overexpression of reactive oxygen species (ROS) and disturbance of the intracellular antioxidant system.
eff↓, abrogated with the use of antioxidants such as N-acetyl-L-cysteine (NAC) and glutathione (GSH), suggesting that formononetin induces apoptosis via ROS production.
p‑ERK↓, formononetin was demonstrated to be a promising molecule that inhibits the phosphorylation of ERK1/2 itself as well as the phosphorylation of downstream ERK substrate (P90RSK)
PTEN↑, Besides the inhibition on AKT activity, formononetin upregulated PTEN expression in bladder cancer T24 cell.
Hif1a↓, The inhibition of AKT pathway by formononetin was mediated through the attenuation of HIF-α expression and inflammatory cytokines release
eff↑, Formononetin was shown to potentiate bortezomib-induced apoptosis in multiple myeloma
eff↑, synergistic effect was evident between formononetin and metformin in cancer treatment.
ChemoSen↑, sensitivity of glioma cells towards doxorubicin was shown to be enhanced by co-treatment with formononetin
HDAC↓, formononetin in doxorubicin-treated glioma cells was associated with formononetin’s suppressive effect on the histone deacetylase (HDAC) 5 expression
*BioAv↑, Due to its lipophilic nature, formononetin is rapidly absorbed into the gut via passive diffusion, with a peak absorption at 30 min ().
*Half-Life↝, Formononetin was determined to have a half-life of ∼2–3 h after oral administration and ∼2 h after intravenous administration
*BioAv↝, At oral administration of formononetin at 20–50 mg/kg, the peak plasma concentration was achieved between (Tmax) 0.5–1 h, while the maximum plasma concentration (Cmax) was determined ranging from 62 nM (17 ng/ml) to 302 nM (81 ng/ml).
*BioAv↑, Meanwhile, the Cmax of 1,302.8 nM (349.5 ng/ml) and 16,956.6 nM (4,548.5 ng/ml) was achieved after intravenous administration of formononetin at 4 and 10 mg/kg, respectively
*BioAv↑, rapidly metabolized and extensively converted into its metabolites daidzein and conjugates of daidzein and formononetin to be excreted, which makes it poorly bioavailable.
*eff↑, Drug delivery systems are strategies employed to overcome the low bioavailability and low water solubility of formononetin to achieve its pharmacological efficacy at minimum dose

7489-

H2,

Molecular Hydrogen in the Treatment of Respiratory Diseases

Review,

Asthma,

*antiOx↑, Molecular hydrogen is gaining increasing attention as an antioxidant, anti-inflammatory, and antiapoptotic agent.
*Inflam↓,
*Apoptosis↓,
*Dose↓, It reaches a maximum level of about 0.78 mM (≈1.6 mg/L) at room temperature with a loss of about 2–5% per 3 min
*Dose↝, It is produced (and consumed) by bacteria of the gut microbiota .The most prominent bacterial phyla involved in this process are the Firmicutes and Bacteroidetes phyla, which include the anaerobic Clostridium species
*eff↑, hydrogen mixed with oxygen at a ratio of 96%-to-4%, known as the Hydrox gas mixture, was used by deep-sea divers to prevent decompression sickness and allow diving to depths of up to 500 m
*ROS↓, The antioxidant activity of H2 is based on two processes: a direct scavenging of the most toxic reactive oxygen and nitrogen species (ROS/RNS),
*RNS↓,
*NRF2↑, H2 activates the Nrf2 (nuclear factor erythroid 2-related factor 2) pathway, a key transcription factor involved in oxidative stress-related responses, including cytoprotective, antioxidant, and detoxifying enzymes such as HO-1
*HO-1↑,
*Fenton↓, removal of free heme and inhibition of the Fenton reaction
*NLRP3↓, the activation of the Nrf2 pathway has been shown to inhibit the NLRP3 (NLR family pyrin domain containing 3) inflammasome,
*NADPH↓, H2 suppresses the activation of the NADPH oxidase pathway and downregulates the expression of NOX2 and NOX4
*NOX4↓,
*NOX↓,
*MPO↓, H2 has been shown to reduce the overactivation of myeloperoxidase (MPO)
*NF-kB↓, would further suppress the NFκB
*TNF-α↓, figure 3
*IL6↓,
*IL1β↓,
*HMGB1↓,
*IL4↑,
*IL10↑,
*M2 MC↑, Additionally, H2 promotes the polarization of macrophages from the proinflammatory M1 type to the anti-inflammatory M2 type
*Treg lymp↝, It also inhibits Th2 responses, restores regulatory T cells (Treg), and, thus, normalizes an overactivated immune system
*Bcl-2↑, upregulate the antiapoptotic factors, including Bcl-2 and Bcl-xl.
*Bcl-xL↑,
*PI3K↑, phenomenon is likely facilitated by the activation of the PI3K/Akt and JAK2/STAT3 signaling pathways
*Akt↑,
*JAK2↑,
*STAT3↑,
*Dose↑, The consumption of certain prebiotics, especially those rich in dietary fiber, indigestible starches, and sugars (lactulose), has been demonstrated to enhance intestinal H2 production through the activity of intestinal flora
*CD4+↑, H2 increased the population of CD4+CD25+Foxp3+ Treg cells, which are often decreased in allergic rhinitis (AR)
*CD25+↑,
*FOXP3↑,
*MDA↓, H2 administration attenuated oxidative stress expressed as lower MDA and other lipid peroxidation markers along with an enhancement in the expression and activity of endogenous antioxidant enzymes such as SOD or CAT
*SOD↑,
*Catalase↑,
*Casp3↓, inhibition of proapoptotic processes like the caspase 3 and 9 pathways
*Casp9↓,
*TBARS↓, drinking of HRW by patients with asthma and COPD leads to an increase in blood oxygen saturation, vitamin E levels, along with lower oxidative stress markers such as thiobarbituric acid reactive substances (TBARS), MDA,
*SpO2↑,
*VitE↓,
*OS↑, COPD:In general, H2 administration has been found to lead to enhanced survival and reduced weight loss [110], improved lung function and static lung compliance, and decreased arterial blood pressure
*Weight↑,
*DNAdam↓, reduction in levels of oxidative DNA damage markers
*PGE2↓, H2 reduced elevated inflammatory markers, including IL-1β, IL-6, TNF-α, prostaglandin E2 (PGE2) [29,65,71,128,130], macrophage protein 1α 2 (MP1α), and monocyte chemoattractant protein-1 (MCP-1)
*MCP1/CCL2↓,
*lipid-P↓, Further, a reduction in oxidative stress markers such as lipid peroxidation and proapoptotic markers, including Bax and caspase-3, was observed.
*TumCP↓, H2-rich medium reduced the colony size and formation of tongue cancer cells and decreased proliferation in human fibrosarcoma and esophageal cancer cells, as well as A549 cells
*tumCV↓, decrease in cell viability, migration, and invasion
*TumCMig↓,
*TumCI↓,
TumW↓, A reduction in tumor weight and size, as well as a lower number of cells of squamous cell carcinoma, was revealed by animal studies.
TumVol↓,
selectivity↑, Notably, as previously reported, H2 administration exhibited no effect on healthy animals or non-cancerous cell lines
QoL↑, Patients reported improved quality of life with better physical status and fewer pulmonary symptoms
ChemoSen↑, In combination with conventional (such as cis-platin) and modern (including antibodies like nivolumab) therapeutics, H2 enhanced drug activity, resulting in enhanced outcomes and improved disease control
chemoP↑, and reduced side effects of the treatment, such as nephrotoxicity, weight loss, insomnia, pain, or hearing loss in the case of radiotherapy
radioP↑, radioprotective effects of H2 are primarily attributed to its hydroxyl radical scavenging activity
ROS↑, As indicated by Yang et al., the latter include the activation of the ROS/NLRP3/caspase-3/gasdermin D-mediated pyroptotic pathways
NLRP3↑,
Casp3↑,
VEGF↓, suppression of vascular endothelial growth factor (VEGF) expression
Wnt↓, H2 result in the suppression of the overactivated Wnt/beta-catenin signaling pathways, which further leads to suppression of tumor progression
β-catenin/ZEB1↓,

7761-

ISL,

Targeting digestive system cancers with isoliquiritigenin: a comprehensive review of antitumor mechanisms

Review,

Var,

Apoptosis↑, via the regulation of apoptosis, autophagy, cell cycle arrest, redox homeostasis, and tumor microenvironment (TME) remodeling.
TumAuto↑,
TumCCA↑,
ROS↑, ROS ↑, JNK ↑, p38 ↑, ERK ↓, STAT3 ↓, NF-κB ↓, IκB ↑, Bcl-2 ↓, Bax ↑, Cleaved caspase-3 ↑, Cleaved PARP ↑, p21 ↑, p27 ↓, Cyclin B1 ↓, CDK1/2 ↓
JNK↑,
p38↑,
STAT3↑,
NF-kB↓,
IκB↑,
Bcl-2↓,
BAX↑,
cl‑Casp3↑,
cl‑PARP↑,
P21↑,
p27/CDKN1B↑,
CycB/CCNB1↑,
CDK1↓,
CDK2↓,
GRP78/BiP↓, ISL also modulates the TME by downregulating GRP78 and inhibiting the PI3K/AKT/mTOR signaling pathway, thereby promoting apoptosis and autophagy
PI3K↓,
Akt↓,
mTOR↓,
eff↑, ISL-17 is a newly synthesized analog of ISL designed to improve its pharmacological properties.
GLUT4↓, ISL inhibits GLUT4-mediated glucose uptake, reduces lactate production and secretion, and suppresses both mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis.
lactateProd↓,
OXPHOS↓,
Glycolysis↓,
BioAv↑, ISL-loaded nanoliposomes represent a novel drug delivery system with excellent self-assembly and biocompatibility properties.
ENO1↓, ISL nanoliposomes suppress the expression of key glycolytic enzymes including Enolase 1 (ENO1), Aldolase A (ALDOA), lactate dehydrogenase A (LDHA), and monocarboxylate transporter 4 (MCT4).
ALDOA↓,
LDHA↓,
MCT4↓,
RadioS↑, ISL also enhances the radiosensitivity of HCC cells by modulating oxidative stress pathways.
Ferroptosis↑, ISL promotes ferroptosis by modulating iron metabolism and enhancing oxidative stress.
i-Iron↑, ISL treatment significantly elevated intracellular ferrous ion (Fe2+) levels, along with a marked increase in ROS and lipid peroxidation.
BioAv↑, Optimization of ISL delivery via two advanced nanocarrier systems has significantly addressed its poor aqueous solubility and limited bioavailability.
Half-Life↓, Furthermore, like many flavonoids, ISL suffers from poor oral bioavailability and rapid metabolic clearance.

533-

MF,

Effects of extremely low-frequency magnetic fields on human MDA-MB-231 breast cancer cells: proteomic characterization

in-vitro,

BC,

MDA-MB-231

1mT, 50Hz for 4 h

in-vitro,

Nor,

MCF10

TumCD↑,
necrosis↑, in normal MCF10A cells
mt-ROS↑, ELF-MF significantly increase the mitochondrial reactive oxygen species production in both MCF-10A and MDA-MB-231 cells, compared to the unexposed cell
other↑, ELF-MF exposed MCF-10A cells exhibited 53 upregulated and 189 downregulated proteins compared with control cells while exposed MDA-MB-231 cells showed 242 upregulated and 86 downregulated proteins compared with the control cells.
*STAT3↓, normal cells
STAT3↑, cancer cells

3357-

QC,

The polyphenol quercetin induces cell death in leukemia by targeting epigenetic regulators of pro-apoptotic genes

in-vitro,

AML,

HL-60

NA,

U937

DNMT1↓, Qu treatment almost eliminates DNMT1 and DNMT3a expression, and this regulation was in part STAT-3 dependent.
DNMT3A↓,
HDAC↓, The treatment also downregulated class I HDACs.
ac‑H3↑, Qu (50 μmol/L) treatment of cell lines for 48 h caused accumulation of acetylated histone 3 and histone 4, resulting in three- to ten fold increases in the promoter region of DAPK1, BCL2L11, BAX, APAF1, BNIP3, and BNIP3L.
ac‑H4↑,
BAX↑,
APAF1↑,
BNIP3↑,
STAT3↑, Quercetin downregulates DNMTs and STAT3

3040-

SK,

Pharmacological Properties of Shikonin – A Review of Literature since 2002

Review,

Var,

Review,

IBD,

Review,

Stroke,

*Half-Life↝, One study using H-shikonin in mice showed that shikonin was rapidly absorbed after oral and intramuscular administration, with a half-life in plasma of 8.79 h and a distribution volume of 8.91 L/kg.
*BioAv↓, shikonin is generally used in creams and ointments, that is, oil-based preparations; indeed, its insolubility in water is usually the cause of its low bioavailability
*BioAv↑, 200-fold increase in the solubility, photostability, and in vitro permeability of shikonin through the formation of a 1 : 1 inclusion complex with hydroxypropyl-β-cyclodextrin.
*BioAv↑, 181-fold increase in the solubility of shikonin in aqueous media in the presence of β-lactoglobulin at a concentra- tion of 3.1 mg/mL
*Inflam↓, anti-inflammatory effect of shikonin
*TNF-α↓, shikonin inhibited TNF-α production in LPS-stimulated rat primary macrophages as well as NF-κB translocation from the cytoplasm to the nucleus.
*other↑, authors found that treatment with shikonin prevented the shortening of the colorectum and decreased weight loss by 5 % while improving the ap- pearance of feces and preventing bloody stools.
*MPO↓, MPO activity was reduced as well as the expression of COX-2, the activation of NF-κB and that of STAT3.
*COX2/PTGS2↓,
*NF-kB↑,
*STAT3↑,
*antiOx↑, Antioxidant Effects of Shikonin
*ROS↓, radical scavenging activity of shikonin
*neuroP↑, shown to exhibit a neuroprotective effect against the damage caused by ischemia/reperfusion in adult male Kunming mice
*SOD↑, it also attenuated neuronal damage and the upregulation of superoxide dismutase, catalase, and glutathione peroxidase activities while reducing the glutathione/glutathione disulfide ratio.
*Catalase↑,
*GPx↑,
*Bcl-2↑, shikonin upregulated Bcl-2, downregulated Bax and prevented cell nuclei from undergoing morphological changes typical of apoptosis.
*BAX↓,
cardioP↑, Two different studies have suggested a possible cardioprotective effect of shikonin that would be related to its anti-inflammatory and antioxidant effects.
AntiCan↑, A wide spectrum of anticancer mechanisms of action have been described for shikonin:
NF-kB↓, suppression of NF-κB-regulated gene products [44],
ROS↑, ROS generation [46],
PKM2↓, inhibition of tumor-specific pyruvate kinase-M2 [47,48]
TumCCA↑, cell cycle arrest [49]
Necroptosis↑, or induction of necroptosis [50],
Apoptosis↑, shikonin at 1 μM induced caspase-dependent apoptosis in U937 cells after 6 h with an increase in DNA fragmentation, intracellular ROS, low mitochondrial membrane potential
DNAdam↑,
MMP↓,
Cyt‑c↑, At 10 μM, shikonin induced a greater release of cytochrome c from the mitochondria and of lactate dehydrogenase,
LDH↝,

Showing Research Papers: 1 to 18 of 18

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 18

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

NA, unassigned(tgid=0) ⓘ

diuretic↑, 1, SpO2↑, 1,

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 4, ARE↑, 1, Catalase↑, 3, Fenton↓, 1, GPx↑, 1, GSH↑, 1, GSTs↑, 1, HDL↑, 1, HO-1↑, 2, lipid-P↓, 1, MDA↓, 1, MPO↓, 2, NOX4↓, 1, NRF2↑, 2, RNS↓, 1, ROS↓, 5, SIRT3↑, 1, SOD↑, 5, SOD1↑, 1, TBARS↓, 1, VitE↓, 1,

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↑, 1,

Core Metabolism/Glycolysis(tgid=4) ⓘ

NADPH↓, 1, PPARγ↑, 1,

Cell Death(tgid=5) ⓘ

Akt↑, 1, Apoptosis↓, 1, BAX↓, 1, Bcl-2↑, 3, Bcl-xL↑, 1, Casp3↓, 2, Casp9↓, 2, GSDMD↓, 1, MAPK↓, 1,

Transcription & Epigenetics(tgid=7) ⓘ

other↑, 1, tumCV↓, 1,

Protein Folding & ER Stress(tgid=8) ⓘ

p‑eIF2α↓, 1, ER Stress↓, 1, p‑PERK↓, 1, UPR↓, 1,

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↓, 1,

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

HDAC2↓, 1, neuroG↑, 1, PI3K↑, 1, PTEN↑, 1, STAT↓, 1, STAT3↓, 1, STAT3↑, 4,

Migration(tgid=13) ⓘ

Treg lymp↝, 1, TumCI↓, 1, TumCMig↓, 1, TumCP↓, 1,

Angiogenesis & Vasculature(tgid=14) ⓘ

ATF4↓, 1, eNOS↑, 1, NO↑, 1, VEGF↑, 1,

Immune & Inflammatory Signaling(tgid=16) ⓘ

CD25+↑, 1, CD4+↑, 1, COX2/PTGS2↓, 1, FOXP3↑, 1, HMGB1↓, 1, IL10↑, 1, IL1β↓, 2, IL4↑, 1, IL6↓, 1, Inflam↓, 4, JAK2↑, 2, M2 MC↑, 1, MCP1/CCL2↓, 1, NF-kB↓, 4, NF-kB↑, 1, PGE2↓, 1, TNF-α↓, 3,

Cellular Microenvironment(tgid=17) ⓘ

NOX↓, 1,

Protein Aggregation(tgid=19) ⓘ

NLRP3↓, 1, NLRP3↑, 1,

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 3, BioAv↑, 5, BioAv↝, 1, Dose↓, 1, Dose↑, 1, Dose↝, 1, eff↑, 2, Half-Life↝, 2, P450↓, 1,

Clinical Biomarkers(tgid=22) ⓘ

IL6↓, 1,

Functional Outcomes(tgid=23) ⓘ

AntiAge↑, 1, AntiCan↑, 1, cardioP↑, 2, hepatoP↑, 2, memory↑, 1, neuroP↑, 2, OS↑, 1, toxicity↝, 2, Weight↑, 1,

Infection & Microbiome(tgid=24) ⓘ

AntiViral↑, 1, Bacteria↓, 1,
Total Targets: 98

Scientific Paper Hit Count for: STAT3, Signal transducer and activator of transcription 3

3 Capsaicin
2 Magnetic Fields
2 Chrysin
1 Berberine
1 Beta-Caryophyllene
1 Betulinic acid
1 Boswellia (frankincense)
1 Cucurbitacin
1 Dandelion Root
1 Emodin
1 Formononetin
1 Hydrogen Gas
1 Isoliquiritigenin
1 Quercetin
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#:373  State#:%  Dir#:2
  wNotes=on  sortOrder:rid,rpid

STAT3 Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress(tgid=1) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

Autophagy & Lysosomes(tgid=9) ⓘ

DNA Damage & Repair(tgid=10) ⓘ

Cell Cycle & Senescence(tgid=11) ⓘ

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

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Barriers & Transport(tgid=15) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Protein Aggregation(tgid=19) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Pathway results for Effect on Normal Cells:

NA, unassigned(tgid=0) ⓘ

Redox & Oxidative Stress(tgid=1) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

DNA Damage & Repair(tgid=10) ⓘ

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

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Cellular Microenvironment(tgid=17) ⓘ

Protein Aggregation(tgid=19) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Infection & Microbiome(tgid=24) ⓘ

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