E-cadherin Cancer Research Results

E-cadherin, E-cadherin: Click to Expand ⟱

Source: HalifaxProj(restore)

Type:

Also known as Cadherin1 (CDH1)
E-cadherin, is a type of cell adhesion molecule that plays a crucial role in maintaining tissue structure and cell-cell interactions. In the context of cancer, E-cadherin has been found to be a tumor suppressor gene.

E-cadherin is a transmembrane protein that mediates cell-cell adhesion through its extracellular domain, which interacts with other E-cadherin molecules on adjacent cells. This interaction helps to maintain tissue integrity and prevent cancer cells from invading surrounding tissues.

In many types of cancer, including breast, colon, and prostate cancer, E-cadherin expression is often reduced or lost.
cell adhesion molecules spanning four families of 1) Integrins (α2β1, α5/β1, αL/β2); 2) Cadherins (E-cad, P-cad, N-cad); 3) Ig-CAMs (VCAM, NCAM, ICAM, Nectins, Necl); and 4) Selectins (E-selectin, P-selectin, L-selectin).

Scientific Papers found: Click to Expand⟱

1333-

AG,

Astragalus polysaccharide inhibits breast cancer cell migration and invasion by regulating epithelial-mesenchymal transition via the Wnt/β-catenin signaling pathway

in-vitro,

BC,

TumCMig↓,
TumCI↓,
Ki-67↓,
TumCP↓,
Snail↓,
Vim↓,
E-cadherin↑,
Wnt↓,
β-catenin/ZEB1↓,

1097-

AG,

Astragalus Inhibits Epithelial-to-Mesenchymal Transition of Peritoneal Mesothelial Cells by Down-Regulating β-Catenin

in-vitro,

Nor,

HMrSV5

in-vivo,

NA,

rat

*EMT↓,
*E-cadherin↑,
*α-SMA↓,
*Vim↓,
*β-catenin/ZEB1↓, rat
*Smad7↑, Astragalus down-regulated β-catenin by enhancing Smad7 expression.

5433-

AG,

Mechanisms of astragalus polysaccharide enhancing STM2457 therapeutic efficacy in m6A-mediated OSCC treatment

vitro+vivo,

OS,

other↓, Combined STM2457 and APS treatment significantly reduced m6A levels, METTL3, HNRNPA2B1, and FOXQ1 expression, and mRNA stability compared to single-drug treatments, approaching or surpassing METTL3 silencing effects.
TumCP↓, The combination markedly suppressed cell proliferation, migration, invasion, and EMT, with increased E-cadherin and decreased N-cadherin levels.
TumCMig↓,
TumCI↓,
EMT↓,
E-cadherin↑,
N-cadherin↓,
TumCG↓, In vivo, combination therapy significantly reduced tumor growth and FOXQ1 expression, outperforming single-drug treatments.

5438-

AG,

Mechanisms of astragalus polysaccharide enhancing STM2457 therapeutic efficacy in mA-mediated OSCC treatment

vitro+vivo,

NA,

STM2457 (50 mg/kg/day) and APS (80 mg/kg/day)

nude mouse

TumCP↓, combination markedly suppressed cell proliferation, migration, invasion, and EMT, with increased E-cadherin and decreased N-cadherin levels.
TumCMig↓,
TumCI↓,
EMT↓,
E-cadherin↑,
N-cadherin↓,

2662-

AL,

Allicin inhibits tubular epithelial-myofibroblast transdifferentiation under high glucose conditions in vitro

in-vitro,

Nor,

HK-2

(HK-2) cultured under high glucose concentrations.

*α-SMA↓, Allicin partially reversed the high-glucose-induced increase in α-SMA, vimentin and collagen I expression (P<0.01 at 20 µg/ml), increased the expression of E-cadherin
*Vim↓,
*COL1↓,
*E-cadherin↑,
*TGF-β1↓, and significantly downregulated the high glucose-induced expression of TGF-β1 and p-ERK1/2 in a dose-dependent manner (P<0.05).
*p‑ERK↓,
*EMT↓, suggested that high glucose concentrations induced the EMT of HK-2 cells, and that allicin was able to inhibit the EMT, potentially via regulation of the ERK1/2-TGF-β1 signaling pathway.

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

1124-

ALA,

Alpha lipoic acid inhibits proliferation and epithelial mesenchymal transition of thyroid cancer cells

in-vitro,

Thyroid,

BCPAP

in-vitro,

Thyroid,

HTH-83

in-vitro,

Thyroid,

CAL-62

in-vitro,

Thyroid,

FTC-133

in-vivo,

NA,

mouse

TumCP↓,
AMPK↑,
mTOR↓,
TumCMig↓,
TumCI↓,
EMT↓,
E-cadherin↑,
β-catenin/ZEB1↓,
Vim↓,
Snail↓,
Twist↓,
TGF-β↓,
p‑SMAD2↓,
TumCG↓, mouse model

2639-

Api,

Plant flavone apigenin: An emerging anticancer agent

Review,

Var,

*antiOx↑, Apigenin (4′, 5, 7-trihydroxyflavone), a major plant flavone, possessing antioxidant, anti-inflammatory, and anticancer properties
*Inflam↓,
AntiCan↑,
ChemoSen↑, Studies demonstrate that apigenin retain potent therapeutic properties alone and/or increases the efficacy of several chemotherapeutic drugs in combination on a variety of human cancers.
BioEnh↑, Apigenin’s anticancer effects could also be due to its differential effects in causing minimal toxicity to normal cells with delayed plasma clearance and slow decomposition in liver increasing the systemic bioavailability in pharmacokinetic studies.
chemoPv↑, apigenin highlighting its potential activity as a chemopreventive and therapeutic agent.
IL6↓, In taxol-resistant ovarian cancer cells, apigenin caused down regulation of TAM family of tyrosine kinase receptors and also caused inhibition of IL-6/STAT3 axis, thereby attenuating proliferation.
STAT3↓,
NF-kB↓, apigenin treatment effectively inhibited NF-κB activation, scavenged free radicals, and stimulated MUC-2 secretion
IL8↓, interleukin (IL)-6, and IL-8
eff↝, The anti-proliferative effects of apigenin was significantly higher in breast cancer cells over-expressing HER2/neu but was much less efficacious in restricting the growth of cell lines expressing HER2/neu at basal levels
Akt↓, Apigenin interferes in the cell survival pathway by inhibiting Akt function by directly blocking PI3K activity
PI3K↓,
HER2/EBBR2↓, apigenin administration led to the depletion of HER2/neu protein in vivo
cycD1/CCND1↓, Apigenin treatment in breast cancer cells also results in decreased expression of cyclin D1, D3, and cdk4 and increased quantities of p27 protein
CycD3↓,
p27↑,
FOXO3↑, In triple-negative breast cancer cells, apigenin induces apoptosis by inhibiting the PI3K/Akt pathway thereby increasing FOXO3a expression
STAT3↓, In addition, apigenin also down-regulated STAT3 target genes MMP-2, MMP-9, VEGF and Twist1, which are involved in cell migration and invasion of breast cancer cells [
MMP2↓,
MMP9↓,
VEGF↓, Apigenin acts on the HIF-1 binding site, which decreases HIF-1α, but not the HIF-1β subunit, thereby inhibiting VEGF.
Twist↓,
MMP↓, Apigenin treatment of HGC-27 and SGC-7901 gastric cancer cells resulted in the inhibition of proliferation followed by mitochondrial depolarization resulting in apoptosis
ROS↑, Further studies revealed apigenin-induced apoptosis in hepatoma tumor cells by utilizing ROS generated through the activation of the NADPH oxidase
NADPH↑,
NRF2↓, Apigenin significantly sensitized doxorubicin-resistant BEL-7402 (BEL-7402/ADM) cells to doxorubicin (ADM) and increased the intracellular concentration of ADM by reducing Nrf2-
SOD↓, In human cervical epithelial carcinoma HeLa cells combination of apigenin and paclitaxel significantly increased inhibition of cell proliferation, suppressing the activity of SOD, inducing ROS accumulation leading to apoptosis by activation of caspas
COX2↓, melanoma skin cancer model where apigenin inhibited COX-2 that promotes proliferation and tumorigenesis
p38↑, Additionally, it was shown that apigenin treatment in a late phase involves the activation of p38 and PKCδ to modulate Hsp27, thus leading to apoptosis
Telomerase↓, apigenin inhibits cell growth and diminishes telomerase activity in human-derived leukemia cells
HDAC↓, demonstrated the role of apigenin as a histone deacetylase inhibitor. As such, apigenin acts on HDAC1 and HDAC3
HDAC1↓,
HDAC3↓,
Hif1a↓, Apigenin acts on the HIF-1 binding site, which decreases HIF-1α, but not the HIF-1β subunit, thereby inhibiting VEGF.
angioG↓, Moreover, apigenin was found to inhibit angiogenesis, as suggested by decreased HIF-1α and VEGF expression in cancer cells
uPA↓, Furthermore, apigenin intake resulted in marked inhibition of p-Akt, p-ERK1/2, VEGF, uPA, MMP-2 and MMP-9, corresponding with tumor growth and metastasis inhibition in TRAMP mice
Ca+2↑, Neuroblastoma SH-SY5Y cells treated with apigenin led to induction of apoptosis, accompanied by higher levels of intracellular free [Ca(2+)] and shift in Bax:Bcl-2 ratio in favor of apoptosis, cytochrome c release, followed by activation casp-9, 12
Bax:Bcl2↑,
Cyt‑c↑,
Casp9↑,
Casp12↑,
Casp3↑, Apigenin also augmented caspase-3 activity and PARP cleavage
cl‑PARP↑,
E-cadherin↑, Apigenin treatment resulted in higher levels of E-cadherin and reduced levels of nuclear β-catenin, c-Myc, and cyclin D1 in the prostates of TRAMP mice.
β-catenin/ZEB1↓,
cMyc↓,
CDK4↓, apigenin exposure led to decreased levels of cell cycle regulatory proteins including cyclin D1, D2 and E and their regulatory partners CDK2, 4, and 6
CDK2↓,
CDK6↓,
IGF-1↓, A reduction in the IGF-1 and increase in IGFBP-3 levels in the serum and the dorsolateral prostate was observed in apigenin-treated mice.
CK2↓, benefits of apigenin as a CK2 inhibitor in the treatment of human cervical cancer by targeting cancer stem cells
CSCs↓,
FAK↓, Apigenin inhibited the tobacco-derived carcinogen-mediated cell proliferation and migration involving the β-AR and its downstream signals FAK and ERK activation
Gli↓, Apigenin inhibited the self-renewal capacity of SKOV3 sphere-forming cells (SFC) by downregulating Gli1 regulated by CK2α
GLUT1↓, Apigenin induces apoptosis and slows cell growth through metabolic and oxidative stress as a consequence of the down-regulation of glucose transporter 1 (GLUT1).

2640-

Api,

Apigenin: A Promising Molecule for Cancer Prevention

Review,

Var,

chemoPv↑, considerable potential for apigenin to be developed as a cancer chemopreventive agent.
ITGB4↓, apigenin inhibits hepatocyte growth factor-induced MDA-MB-231 cells invasiveness and metastasis by blocking Akt, ERK, and JNK phosphorylation and also inhibits clustering of β-4-integrin function at actin rich adhesive site
TumCI↓,
TumMeta↓,
Akt↓,
ERK↓,
p‑JNK↓,
*Inflam↓, The anti-inflammatory properties of apigenin are evident in studies that have shown suppression of LPS-induced cyclooxygenase-2 and nitric oxide synthase-2 activity and expression in mouse macrophages
*PKCδ↓, Apigenin has been reported to inhibit protein kinase C activity, mitogen activated protein kinase (MAPK), transformation of C3HI mouse embryonic fibroblasts and the downstream oncogenes in v-Ha-ras-transformed NIH3T3 cells (43, 44).
*MAPK↓,
EGFR↓, Apigenin treatment has been shown to decrease the levels of phosphorylated EGFR tyrosine kinase and of other MAPK and their nuclear substrate c-myc, which causes apoptosis in anaplastic thyroid cancer cells
CK2↓, apigenin has been shown to inhibit the expression of casein kinase (CK)-2 in both human prostate and breast cancer cells
TumCCA↑, apigenin induces a reversible G2/M and G0/G1 arrest by inhibiting p34 (cdc2) kinase activity, accompanied by increased p53 protein stability
CDK1↓, inhibiting p34 (cdc2) kinase activity
P53↓,
P21↑, Apigenin has also been shown to induce WAF1/p21 levels resulting in cell cycle arrest and apoptosis in androgen-responsive human prostate cancer
Bax:Bcl2↑, Apigenin treatment has been shown to alter the Bax/Bcl-2 ratio in favor of apoptosis, associated with release of cytochrome c and induction of Apaf-1, which leads to caspase activation and PARP-cleavage
Cyt‑c↑,
APAF1↑,
Casp↑,
cl‑PARP↑,
VEGF↓, xposure of endothelial cells to apigenin results in suppression of the expression of VEGF, an important factor in angiogenesis via degradation of HIF-1α protein
Hif1a↓,
IGF-1↓, oral administration of apigenin suppresses the levels of IGF-I in prostate tumor xenografts and increases levels of IGFBP-3, a binding protein that sequesters IGF-I in vascular circulation
IGFBP3↑,
E-cadherin↑, apigenin exposure to human prostate carcinoma DU145 cells caused increase in protein levels of E-cadherin and inhibited nuclear translocation of β-catenin and its retention to the cytoplasm
β-catenin/ZEB1↓,
HSPs↓, targets of apigenin include heat shock proteins (61), telomerase (68), fatty acid synthase (69), matrix metalloproteinases (70), and aryl hydrocarbon receptor activity (71) HER2/neu (72), casein kinase 2 alpha
Telomerase↓,
FASN↓,
MMPs↓,
HER2/EBBR2↓,
CK2↓,
eff↑, The combination of sulforaphane and apigenin resulted in a synergistic induction of UGT1A1
AntiAg↑, Apigenin inhibit platelet function through several mechanisms including blockade of TxA
eff↑, ex vivo anti-platelet effect of aspirin in the presence of apigenin, which encourages the idea of the combined use of aspirin and apigenin in patients in which aspirin fails to properly suppress the TxA
FAK↓, Apigenin inhibits expression of focal adhesion kinase (FAK), migration and invasion of human ovarian cancer A2780 cells.
ROS↑, Apigenin generates reactive oxygen species, causes loss of mitochondrial Bcl-2 expression, increases mitochondrial permeability, causes cytochrome C release, and induces cleavage of caspase 3, 7, 8, and 9 and the concomitant cleavage of the inhibitor
Bcl-2↓,
Cyt‑c↑,
cl‑Casp3↑,
cl‑Casp7↑,
cl‑Casp8↑,
cl‑Casp9↑,
cl‑IAP2↑,
AR↓, significant decrease in AR protein expression along with a decrease in intracellular and secreted forms of PSA. Apigenin treatment of LNCaP cells
PSA↓,
p‑pRB↓, apigenin inhibited hyperphosphorylation of the pRb protein
p‑GSK‐3β↓, Inhibition of p-Akt by apigenin resulted in decreased phosphorylation of GSK-3beta.
CDK4↓, both flavonoids exhibited cell growth inhibitory effects which were due to cell cycle arrest and downregulation of the expression of CDK4
ChemoSen↑, Combination therapy of gemcitabine and apigenin enhanced anti-tumor efficacy in pancreatic cancer cells (MiaPaca-2, AsPC-1)
Ca+2↑, apigenin in neuroblastoma SH-SY5Y cells resulted in increased apoptosis, which was associated with increases in intracellular free [Ca(2+)] and Bax:Bcl-2 ratio, mitochondrial release of cytochrome c and activation of caspase-9, calpain, caspase-3,12
cal2↑,

210-

Api,

Apigenin inhibits migration and invasion via modulation of epithelial mesenchymal transition in prostate cancer

in-vitro,

Pca,

DU145

 10-80 uM

 1 uM/ml (10-80 uM) (24-48 hrs)

EMT↓,
E-cadherin↑,
Snail↓,
Vim↓,

244-

Api,

Inhibition of the STAT3 signaling pathway contributes to apigenin-mediated anti-metastatic effect in melanoma

in-vivo,

Melanoma,

B16-F10

 10 and 20 uM

 mice

in-vivo,

Melanoma,

A375

in-vivo,

Melanoma,

G361

STAT3↓,
MMP2↓,
MMP9↓,
VEGF↓,
Twist↓, Twist1
E-cadherin↑,
N-cadherin↓,
EMT↓,

3382-

ART/DHA,

Repurposing Artemisinin and its Derivatives as Anticancer Drugs: A Chance or Challenge?

Review,

Var,

1.20–15.2 μM

AntiCan↑, antimalarial drug, artemisinin that has shown anticancer activities in vitro and in vivo.
toxicity↑, safety of artemisinins in long-term cancer therapy requires further investigation.
Ferroptosis↑, Artemisinins acts against cancer cells via various pathways such as inducing apoptosis (Zhu et al., 2014; Zuo et al., 2014) and ferroptosis via the generation of reactive oxygen species (ROS) (Zhu et al., 2021) and causing cell cycle arrest
ROS↑,
TumCCA↑,
BioAv↝, absolute bioavailability was estimated to be 21.6%. ART has good solubility and is not lipophilic
eff↝, ART would not distribute well to the tissues and might be more effective in treating cancers such as leukemia, hepatocellular carcinoma (HCC), or renal cell carcinoma because the liver and kidney are highly perfused organs.
Half-Life↓, Pharmacokinetic studies showed a relatively short t1/2 of artemisinins. For ART, t1/2 was 0.41 h
Ferritin↓, Figure 3
GPx4↓,
NADPH↓,
GSH↓,
BAX↑,
Cyt‑c↑,
cl‑Casp3↑,
VEGF↓, angiogenesis
IL8↓,
COX2↓,
MMP9↓,
E-cadherin↑,
MMP2↓,
NF-kB↓,
p16↑, cell cycle arrest
CDK4↓,
cycD1/CCND1↓,
p62↓, autophagy
LC3II↑,
EMT↓, suppressing EMT and CSCs
CSCs↓,
Wnt↓, Depress Wnt/β-catenin signaling pathway
β-catenin/ZEB1↓,
uPA↓, Inhibit u-PA activity, protein and mRNA expression
TumAuto↑, Emerging evidence suggests that autophagy induction is one of the molecular mechanisms underlying anticancer activity of artemisinins
angioG↓, Inhibition of Angiogenesis
ChemoSen↑, Many studies also reported that the use of artemisinins sensitized cancer cells to conventional chemotherapy and exerted a synergistic effect on apoptosis, inhibition of cell growth, and a reduction of cell viability, leading to a lower IC50 value

3391-

ART/DHA,

Antitumor Activity of Artemisinin and Its Derivatives: From a Well-Known Antimalarial Agent to a Potential Anticancer Drug

Review,

Var,

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↑,

570-

ART/DHA,

Artemisinin and its derivatives can significantly inhibit lung tumorigenesis and tumor metastasis through Wnt/β-catenin signaling

vitro+vivo,

NSCLC,

A549

76.95 μM

mice

vitro+vivo,

NSCLC,

H1299

TumCCA↑, arresting cell cycle in G1 phase.
CSCs↓,
TumCI↓,
TumCMig↓,
TumCG↓,
Wnt/(β-catenin)↓, main pathway
Nanog↓,
SOX2↓,
OCT4↓, oct3/4
N-cadherin↓,
Vim↓,
E-cadherin↑,

558-

ART/DHA,

Artemisinin and Its Synthetic Derivatives as a Possible Therapy for Cancer

Review,

NA,

ROS↑,
oncosis↑, low doses of artesunate induced oncosis-like cell death
Apoptosis↑, higher doses of art
LysoPr↑,
TumAuto↑,
Wnt/(β-catenin)↑,
AMP↓,
NF-kB↓,
Myc↓,
CREBBP↓,
mTOR↓,
E-cadherin↑,

5415-

ASA,

The Anti-Metastatic Role of Aspirin in Cancer: A Systematic Review

Review,

Var,

TumMeta↓, The included studies demonstrated that aspirin suppresses metastatic dissemination across multiple cancer types through coordinated platelet-dependent and tumor-intrinsic mechanisms.
COX1↓, Aspirin consistently inhibited platelet aggregation and COX-1-dependent TXA2 production, disrupting platelet–tumor cell interactions, intravascular metastatic niche formation, and platelet-mediated immune suppression.
TXA2↓,
AntiAg↑, Beyond platelet effects, aspirin suppressed EMT, migration, and invasion through modulation of EMT transcriptional regulators and inflammatory signaling pathways.
EMT↓,
TumCMig↓,
TumCI↓,
AMPK↑, Additional mechanisms included activation of AMPK, inhibition of c-MYC signaling, regulation of redox-responsive pathways and impairment of anoikis resistance.
cMyc↓,
PGE2↓, Importantly, oral aspirin (20 mg/kg/day; human-equivalent ≈ 150 mg/day), administered before tumor cell injection, prevented platelet-induced metastatic enhancement and suppressed TXA2 and PGE2 production.
Dose↑, medium and high doses of aspirin reduced pulmonary metastatic burden by more than 50%, whereas low-dose aspirin was ineffective.
RadioS↑, Wang et al. [45] demonstrated that low-dose aspirin suppresses radiotherapy-induced release of immunosuppressive exosomes in breast cancer, restoring NK-cell proliferation and enhancing antitumor immunity in vivo.
PD-L1↓, Similarly, Xiao et al. [46] showed that aspirin epigenetically downregulates PD-L1 expression by inhibiting KAT5-dependent histone acetylation, thereby restoring T-cell activation
E-cadherin↑, Aspirin restored E-cadherin expression and suppressed EMT regulators, including Slug, vimentin, Twist, MMP-2, and MMP-9.
EMT↓,
Slug↓,
Vim↓,
Twist↓,
MMP2↓,
MMP9↓,
other↑, definitive conclusions regarding clinical efficacy across cancer types cannot yet be drawn. Nevertheless, the consistency of mechanistic signals across experimental systems supports further investigation of aspirin as a low-cost adjunct in oncology

4816-

ASTX,

Potent carotenoid astaxanthin expands the anti-cancer activity of cisplatin in human prostate cancer cells

in-vitro,

Pca,

*antiOx↑, ASX has protective effects on various diseases, such as Parkinson’s disease and cancer by showing potent antioxidant and anti-inflammatory properties.
*Inflam↓,
ChemoSen↑, Additionally, we determined that it exhibited synergistic action with cisplatin and significantly enhanced apoptotic cell death in PCa cells. (beware of dose required for this?)
E-cadherin↑, graphical abstract
N-cadherin↓,
VEGF↓,
cMyc↓,
PSA↓,
cl‑Casp3↑, ASTX improves the cisplatin induces caspase 3 cleavage and PARP1 activation
PARP1↑,

999-

Ba,

Baicalin Inhibits EMT through PDK1/AKT Signaling in Human Nonsmall Cell Lung Cancer

in-vitro,

Lung,

H460

TumCP↓,
p‑PDK1↓,
p‑Akt↓,
EMT↓, baicalin effectively inhibited the EMT of NSCLC.
E-cadherin↑,
Vim↓,

1098-

BA,

Baicalein inhibits fibronectin-induced epithelial–mesenchymal transition by decreasing activation and upregulation of calpain-2

in-vitro,

Nor,

MCF10

in-vivo,

NA,

mouse

*TumCMig↓,
*F-actin↓,
*E-cadherin↑,
*ZO-1↑,
*N-cadherin↓,
*Vim↓,
*Snail↓,
*cal2↓, baicalein inhibited calpain-2 by decreasing intracellular calcium ion levels
*Ca+2↝, Effects of baicalein on fibronectin (FN)-induced intracellular elevation of Ca2+ Returns elevated levels close to back to original levels.

2473-

BA,

Baicalin Inhibits EMT through PDK1/AKT Signaling in Human Nonsmall Cell Lung Cancer

in-vitro,

Lung,

A549

30uM

85.12 uM

in-vitro,

Nor,

BEAS-2B

140.7 μM

normal cells

in-vitro,

Lung,

H460

53.93 uM

EMT↓, Baicalin impedes EMT by inhibiting the PDK1/AKT pathway in human NSCLC and thus may be an effective alternative treatment for carcinoma and a new candidate antimetastasis drug.
PDK1↓, Baicalin Inhibited PDK1/AKT Signaling Pathway in NSCLC
Akt↓,
TumCMig↓, At 30 μM, this compound considerably inhibited migration and clone formation in NSCLC cell lines.
E-cadherin↑,
Vim↓, figure 3

2617-

Ba,

Potential of baicalein in the prevention and treatment of cancer: A scientometric analyses based review

Review,

Var,

Ca+2↑, MDA-MB-231 ↑Ca2+
MMP2↓, MDA-MB-231 ↓MMP-2/9
MMP9↓,
Vim↓, ↓Vimentin, ↓SNAIL, ↑E-cadherin, ↓Wnt1, ↓β-catenin
Snail↓,
E-cadherin↑,
Wnt↓,
β-catenin/ZEB1↓,
p‑Akt↓, MCF-7 ↓p-Akt, ↓p-mTOR, ↓NF-κB
p‑mTOR↓,
NF-kB↓,
i-ROS↑, MCF-7 ↑Intracellular ROS, ↓Bcl-2, ↑Bax, ↑cytochrome c, ↑caspase-3/9
Bcl-2↓,
BAX↑,
Cyt‑c↑,
Casp3↑,
Casp9↑,
STAT3↓, 4T1, MDA-MB-231 ↓STAT3, ↓ IL-6
IL6↓,
MMP2↓, HeLa ↓MMP-2, ↓MMP-9
MMP9↓,
NOTCH↓, ↓Notch 1
PPARγ↓, ↓PPARγ
p‑NRF2↓, HCT-116 ↓p-Nrf2
HK2↓, ↓HK2, ↓LDH-A, ↓PDK1, ↓glycolysis, PTEN/Akt/HIF-1α regulation
LDHA↓,
PDK1↓,
Glycolysis↓,
PTEN↑, Furthermore, baicalein inhibited hypoxia-induced Akt phosphorylation by promoting PTEN accumulation, thereby attenuating hypoxia-inducible factor-alpha ( HIF-1a) expression in AGS cells.
Akt↓,
Hif1a↓,
MMP↓, SGC-7901 ↓ΔΨm
VEGF↓, ↓VEGF, ↓VEGFR2
VEGFR2↓,
TOP2↓, ↓Topoisomerase II
uPA↓, ↓u-PA, ↓TIMP1, ↓TIMP2
TIMP1↓,
TIMP2↓,
cMyc↓, ↓β-catenin, ↓c-Myc, ↓cyclin D1, ↓Axin-2
TrxR↓, EL4 ↓Thioredoxin reductase, ↑ASK1,
ASK1↑,
Vim↓, ↓vimentin
ZO-1↑, ↑ZO-1
E-cadherin↑, ↑E-cadherin
SOX2↓, PANC-1, BxPC-3, SW1990 ↓Sox-2, ↓Oct-4, ↓SHH, ↓SMO, ↓Gli-2
OCT4↓,
Shh↓,
Smo↓,
Gli1↓,
N-cadherin↓, ↓N-cadherin
XIAP↓, ↓XIAP

2296-

Ba,

The most recent progress of baicalein in its anti-neoplastic effects and mechanisms

Review,

Var,

CDK1↓, graphical abstract
Cyc↓,
p27↑,
P21↑,
P53↑,
TumCCA↑, Cell cycle arrest
TumCI↓, Inhibit invastion
MMP2↓,
MMP9↓,
E-cadherin↑,
N-cadherin↓,
Vim↓,
LC3A↑,
p62↓,
p‑mTOR↓,
PD-L1↓,
CAFs/TAFs↓,
VEGF↓,
ROCK1↓,
Bcl-2↓,
Bcl-xL↓,
BAX↑,
ROS↑,
cl‑PARP↑,
Casp3↑,
Casp9↑,
PTEN↑, A549, H460
MMP↓, ↓mitochondrial transmembrane potential, redistribution of cytochrome c,
Cyt‑c↑,
Ca+2↑, ↑Ca2+
PERK↑, ↑PERK, ↑IRE1α, ↑CHOP,
IRE1↑,
CHOP↑,
Copper↑, ↑Cu+2
Snail↓, ↓Snail, ↓vimentin, ↓Twist1,
Vim↓,
Twist↓,
GSH↓, ↑ROS, ↓GSH, ↑MDA, ↓MMP, ↓NRF2, ↓HO-1, ↓GPX4, ↓FTH1, ↑TFR1, ↓p-JAK2, ↓p-STAT3
NRF2↓,
HO-1↓,
GPx4↓,
XIAP↓, ↓Bcl-2, ↓Bcl-xL, ↓XIAP, ↓surviving
survivin↓,
DR5↑, ↑ROS, ↑DR5

1398-

BBR,

Berberine inhibits the progression of renal cell carcinoma cells by regulating reactive oxygen species generation and inducing DNA damage

in-vitro,

Kidney,

TumCP↓,
TumCMig↓,
ROS↑,
Apoptosis↑,
BAX↑,
BAD↑,
Bak↑,
Cyt‑c↑,
cl‑Casp3↑,
cl‑Casp9↑,
E-cadherin↑,
TIMP1↑,
γH2AX↑,
Bcl-2↓,
N-cadherin↓,
Vim↓,
Snail↓,
RAD51↓,
PCNA↓,

1102-

BBR,

Berberine suppressed epithelial mesenchymal transition through cross-talk regulation of PI3K/AKT and RARα/RARβ in melanoma cells

in-vitro,

Melanoma,

B16-BL6

TumCMig↓,
TumCI↓,
EMT↓,
p‑PI3K↓,
p‑Akt↓,
RARα↓,
RARβ↑,
RARγ↑,
E-cadherin↑,
N-cadherin↓,

1031-

BCA,

Biochanin A Suppresses Tumor Progression and PD-L1 Expression via Inhibiting ZEB1 Expression in Colorectal Cancer

vitro+vivo,

CRC,

HCT116

20-100uM

vitro+vivo,

CRC,

SW-620

PD-L1↓,
TumCG↓,
Zeb1↓, ZEB1 is a main regulator of PD-L1 expression in CRC.
E-cadherin↑,
N-cadherin↓,
EMT↓, blocked the EMT process in CRC.

2738-

BetA,

Betulinic Acid Suppresses Breast Cancer Metastasis by Targeting GRP78-Mediated Glycolysis and ER Stress Apoptotic Pathway

in-vitro,

BC,

MDA-MB-231

in-vitro,

BC,

BT549

in-vivo,

NA,

mice

TumCI↓, BA inhibited invasion and migration of highly aggressive breast cancer cells.
TumCMig↓,
Glycolysis↓, Moreover, BA could suppress aerobic glycolysis of breast cancer cells presenting as a reduction of lactate production, quiescent energy phenotype transition, and downregulation of aerobic glycolysis-related proteins.
lactateProd↓, lactate production in both MDA-MB-231 and BT-549 cells was significantly reduced following BA administration
GRP78/BiP↑, (GRP78) was also identified as the molecular target of BA in inhibiting aerobic glycolysis. BA treatment led to GRP78 overexpression, and GRP78 knockdown abrogated the inhibitory effect of BA on glycolysis.
ER Stress↑, Further studies demonstrated that overexpressed GRP78 activated the endoplasmic reticulum (ER) stress sensor PERK.
PERK↑,
p‑eIF2α↑, Subsequent phosphorylation of eIF2α led to the inhibition of β-catenin expression, which resulted in the inhibition of c-Myc-mediated glycolysis.
β-catenin/ZEB1↓,
cMyc↓, These findings suggested that BA inhibited the β-catenin/c-Myc pathway by interrupting the binding between GRP78 and PERK and ultimately suppressed the glycolysis of breast cancer cells.
ROS↑, (i) the induction of cancer cell apoptosis via the mitochondrial pathway induced by the release of soluble factors or generation of reactive oxygen species (ROS)
angioG↓, (ii) the inhibition of angiogenesis [24];
Sp1/3/4↓, (iii) the degradation of transcription factor specificity protein 1 (Sp1)
DNAdam↑, (iv) the induction of DNA damage by suppressing topoisomerase I
TOP1↓,
TumMeta↓, BA Inhibits Metastasis of Highly Aggressive Breast Cancer Cells
MMP2↓, BA significantly decreased the expression of MMP-2 and MMP-9 secreted by breast cancer cells
MMP9↓,
N-cadherin↓, BA downregulated the levels of N-cadherin and vimentin as the mesenchymal markers, while increased E-cadherin which is an epithelial marker (Figure 2(c)), validating the EMT inhibition effects of BA in breast cancer cells.
Vim↓,
E-cadherin↑,
EMT↓,
LDHA↓, the levels of glycolytic enzymes, including LDHA and p-PDK1/PDK1, were all decreased in a dose-dependent manner by BA
p‑PDK1↓,
PDK1↓,
ECAR↓, extracellular acidification rate (ECAR), which reflects the glycolysis activity, was retarded following BA administration.
OCR↓, oxygen consumption rate (OCR), which is a marker of mitochondrial respiration, was also decreased simultaneously
Hif1a↓, BA could reduce prostate cancer angiogenesis via inhibiting the HIF-1α/stat3 pathway [39]
STAT3↓,

2741-

BetA,

Betulinic acid triggers apoptosis and inhibits migration and invasion of gastric cancer cells by impairing EMT progress

in-vitro,

GC,

SNU16

in-vitro,

GC,

NCI-N87

in-vivo,

NA,

(40 mg/kg)

mice

TumCG↓, BA had significant cytotoxic and inhibitory effects on GC cells in a dose- and time-dependent manner.
TumCMig↓, BA inhibited the migratory and invasive abilities of SNU-16 cells
TumCI↓,
N-cadherin↓, relative expression level of N-cadherin in SNU-16 cells was drastically down-regulated, and the expression of E-cadherin in SNU-16 cells was distinctly up-regulated in comparison to that in the control group, implying a break in the EMT process.
E-cadherin↑,
EMT↓,
Ki-67↓, proportions of Ki-67-positive and MMP2-positive cells were significantly lower in the tumour sections of the BA-treated group than those in the sections of the control group
MMP2↓,

734-

Bor,

Boric Acid Affects the Expression of DNA Double-Strand Break Repair Factors in A549 Cells and A549 Cancer Stem Cells: An In Vitro Study

in-vitro,

Lung,

A549

1 to 100 mM)

effects start at 10mM

ATM↓, 30x
Casp3↑,
E-cadherin↑,

733-

Bor,

The analysis of boric acid effect on epithelial-mesenchymal transition of CD133 + CD117 + lung cancer stem cells

in-vitro,

Lung,

1-100mM

Targeting lung cancer stem cells (LC-SCs) for metastasis

Snail↑,
ITGB1↑,
ITGA5↑,
COL1A1↓, 50 mM 24 h of BA treatment could be more beneficial as it reduces the expression of COL1A1 in cancer stem cells.
LAMA5↑,
MMP3↓,
Vim↓,
E-cadherin↑,
EMT↓, inhibit the EMT of lung cancer stem cells by reducing E-cadherin and Collagen-1 expression.
Zeb1↑,

1422-

Bos,

Boswellic acid exerts antitumor effects in colorectal cancer cells by modulating expression of the let-7 and miR-200 microRNA family

in-vitro,

CRC,

20-40uM

in-vivo,

NA,

(0, 50, 100 and 200mg/kg/day for 28 days

mice

5LO↓, boswellic acids, is known to be a non-redox and non-competitive inhibitor of 5-lipoxygenase
TumCG↓,
Let-7↑,
miR-200b↑, AKBA significantly up-regulated expression of the let-7 and miR-200 families in various CRC cell lines
NF-kB↓,
cMyc↓,
cycD1/CCND1↓,
MMP9↓,
CXCR4↓,
VEGF↓,
Bcl-xL↓,
survivin↓,
IAP1↓,
XIAP↓,
TumCG↓,
CDK6↓,
Vim↓,
E-cadherin↑,

5698-

BRU,

Brusatol suppresses STAT3-driven metastasis by downregulating epithelial-mesenchymal transition in hepatocellular carcinoma

in-vitro,

HCC,

TumCMig↓, Brusatol affects migration and invasion ability of HCC cells.
EMT↓, Brusatol affects EMT process through modulation of STAT3 activation pathway.
STAT3↓, BT concentration-dependently inhibited constitutive STAT3 activation
E-cadherin↑, BT treatment restored the expression of Occludin, E-cadherin (epithelial markers) while suppressing the levels of different mesenchymal markers in HCC cells and tumor tissues.
NRF2↓, Brusatol (BT) is a natural quassinoid that has been demonstrated as an inhibitor of nuclear factor erythroid 2-related factor-2 (Nrf-2) by several research groups
ChemoSen↑, BT can interfere with Nrf-2 signaling in cancer cells to enhance the chemotherapeutic potential of paclitaxel, cisplatin, 5-fluorouracil, gemcitabine, carboplatin, and etoposide
RadioS↑, and also increase the radiosensitivity of lung cancer cells
DNAdam↑, BT disrupted Nrf-2 dependent transcriptional activity and induced oxidative DNA damage [33].
TumCMig↓, BT suppresses migration as well as invasion in HCC cells
TumCI↓,
toxicity↓, BT treatment did not impart notable toxicity in tested mice

2047-

Buty,

Sodium butyrate inhibits migration and induces AMPK-mTOR pathway-dependent autophagy and ROS-mediated apoptosis via the miR-139-5p/Bmi-1 axis in human bladder cancer cells

in-vitro,

CRC,

T24/HTB-9

0-10mM

in-vitro,

Nor,

SV-HUC-1

in-vitro,

Bladder,

5637

in-vivo,

NA,

200 mg/kg/day, i.g., n = 5

mice

HDAC↓, Sodium butyrate (NaB) is a histone deacetylase inhibitor and exerts remarkable antitumor effects in various cancer cells
AntiTum↑,
TumCMig↓, NaB inhibited migration
AMPK↑, induced AMPK/mTOR pathway-activated autophagy and reactive oxygen species (ROS) overproduction via the miR-139-5p/Bmi-1 axis
mTOR↑,
TumAuto↑,
ROS↑, NaB initiates ROS overproduction
miR-139-5p↑, NaB upregulates miR-139-5p and depletes Bmi-1 in bladder cancer cells
BMI1↓,
TumCI?, NaB significantly inhibited cell migration dose-dependently
E-cadherin↑, E-cadherin was markedly increased, while the expression of N-cadherin, Vimentin, and Snail was decreased
N-cadherin↓,
Vim↓,
Snail↓,
cl‑PARP↑, increased expression levels of cleaved PARP, cleaved caspase-3, and Bax and the concurrent decrease in Bcl-2 and Bcl-xl
cl‑Casp3↑,
BAX↑,
Bcl-2↓,
Bcl-xL↓,
MMP↓, impairs mitochondrial membrane potential
PINK1↑, activates the PINK1/ PARKIN pathway
PARK2↑,
TumMeta↓, NaB inhibits tumor metastasis and growth in vivo
TumCG↓,
LC3II↑, a significant increase in the levels of cleaved caspase3, p-AMPK, and LC3B-II along with decreased Bmi-1 and Vimentin
p62↓, elevated LC3B-II levels and degradation of p62
eff↓, NAC abolished the impairment of MMP and ROS overproduction. Interestingly, NAC also significantly inhibited apoptosis induced by NaB

1651-

CA,

PBG,

Caffeic acid and its derivatives as potential modulators of oncogenic molecular pathways: New hope in the fight against cancer

Review,

Var,

Apoptosis↑,
TumCCA↓, CAPE (1-80 uM) can stimulate apoptosis and cell cycle arrest (G1 phase
TumCMig↓,
TumMeta↓,
ChemoSen↑,
eff↑, Nanoparticles promote therapeutic effect of CA and CAPE in reducing cancer cell malignancy.
eff↑, improve capacity of CA and CAPE in cancer suppression, it has been co-administered with other anti-tumor compounds such as gallic acid
eff↓, Currently, solvent extraction is utilized by methanol and ethyl acetate combination at high temperatures. However, a low amount of CA is yielded via this pathway
eff↝, Decyl CA (DCA) is a novel derivative of CA but its role in affecting colorectal cancer has not been completely understood.
Dose∅, The CAPE administration (0-60 uM) induces both autophagy and apoptosis in C6 glioma cells.
AMPK↑, CAPE induces autophagy via AMPK upregulation.
p62↓, CAPE can induce autophagy via p62 down-regulation and LC3-II upregulation
LC3II↑,
Ca+2↑, CA (0-1000 uM) enhances Ca2+ accumulation in cells in a concentration-dependent manner
Bax:Bcl2↑, CA can promote Bax/Bcl-2 ratio i
CDK4↑, The administration of CAPE (1–80 μM) can stimulate apoptosis and cell cycle arrest (G1 phase) via upregulation of Bax, CDK4, CDK6 and Rb
CDK6↑,
RB1↑,
EMT↓, CAPE has demonstrated high potential in inhibiting EMT in nasopharyngeal caner via enhancing E-cadherin levels, and reducing vimentin and β-catenin levels.
E-cadherin↑,
Vim↓,
β-catenin/ZEB1↓,
NF-kB↓,
angioG↑, CAPE (0.01-1ug/ml) inhibited angiogenesis via VEGF down-regulation
VEGF↓,
TSP-1↑, and furthermore, CAPE is capable of increasing TSP-1 levels
MMP9↓, CAPE was found to reduce MMP-9 expression
MMP2↓, CAPE can also down-regulate MMP-2
ChemoSen↑, role of CA and its derivatives in enhancing therapy sensitivity of cancer cells.
eff↑, CA administration (100 uM) alone or its combination with metformin (10 mM) can induce AMPK signaling
ROS↑, CA can promote ROS levels to induce cell death in human squamous cell carcinoma
CSCs↓, CA can reduce self-renewal capacity of CSCs and their migratory ability in vitro and in vivo.
Fas↑, CAPE (0-100 uM) is capable of inducing Fas signaling to promote p53 expression, leading to apoptotic cell death via Bax and caspase activation
P53↑,
BAX↑,
Casp↑,
β-catenin/ZEB1↓, anti-tumor activity of CAPE is mediated via reducing β-catenin levels
NDRG1↑, CAPE (30 uM) can promote NDRG1 expression via MAPK activation and down-regulation of STAT3
STAT3↓,
MAPK↑, CAPE stimulates mitogen-activated protein kinase (MAPK) and ERK
ERK↑,
eff↑, Res, thymoquinone and CAPE mediate lung tumor cell death via Bax upregulation and Bcl-2 down-regulation.
eff↑, co-administration of CA (100 Î¼M) and metformin (10 mM) is of interest in cervical squamous cell carcinoma therapy.
eff↑, in addition to CA, propolis contains other agents such as chrysin, p-coumaric acid and ferulic acid that are beneficial in tumor suppression.

5849-

CAP,

The Impact of TRPV1 on Cancer Pathogenesis and Therapy: A Systematic Review

Review,

Var,

TRPV1↑, TRPV1 belongs to the transient receptor potential channel vanilloid subfamily and is also known as the capsaicin receptor and vanilloid receptor 1 (VR1).
Ca+2↑, The activation of TRPV1 induces the cellular influx of Ca2+ and Na+ ions 17-19, and the excess intracellular Ca2+ and Na+ leads to cell death 20.
TumCD↑,
TumCCA↑, Induced cell cycle arrest in G0/G1 phase and apoptosis by activating p53 to upregulate Fas/CD95 in TRPV1-overexpressing cells
Apoptosis↑,
P53↑,
Fas↑,
PI3K↑, Activated PI3K and p44/42 MAPK pathways to suppress ceramide production and increased androgen receptor expression
AR↑,
STAT3↓, attenuating STAT3 phosphorylation
ROS↑, Induced apoptosis by producing ROS originating from the mitochondria
MMP↓, Disrupted mitochondrial membrane potential and suppressed ATP synthesis to induce apoptosis
ATP↓,
CHOP↑, Stimulated ROS generation, increased CHOP expression level, and promoted apoptosis
TumCMig↓, As TRPV1 serves as the main Ca2+-influx channel, it is reasonable to suggest that TRPV1 could act as an enhancer or inhibitor of migration and invasion in a tissue- or cell-specific manner.
Twist↓, Capsaicin downregulated Tiwst1, Snail1, MMP2, and MMP9 and upregulated E-cadherin
Snail↓,
MMP2↓,
MMP9↓,
E-cadherin↑,

1517-

CAP,

Capsaicin Inhibits Multiple Bladder Cancer Cell Phenotypes by Inhibiting Tumor-Associated NADH Oxidase (tNOX) and Sirtuin1 (SIRT1)

in-vitro,

Bladder,

TSGH8301

in-vitro,

CRC,

T24/HTB-9

ENOX2↓, capsaicin downregulates tNOX expression
TumCCA↑, Capsaicin Downregulates tNOX and Induces Cell Cycle Arrest at G1 Phase
ERK↓, inhibit the activation of ERK
p‑FAK↓,
p‑pax↓,
TumCMig↓,
EMT↓,
SIRT1↓, downregulation of sirtuin 1 (SIRT1) in these tNOX-knockdown cells
Dose∅, 100 and 200 μM effectively reduced tNOX expression in bladder cancer TSGH8301 and T24
ROS↑, capsaicin dose-dependently increased ROS generation
MMP↓,
Bcl-2↓,
Bak↑,
cl‑PARP↑,
Casp3↑,
SIRT1↓, 100 and 200 μM capsaicin decreased SIRT1 expression
ac‑P53↑, concurrently increased p53 acetylation
BIM↑, enhanced the expression level of Bim
p‑RB1↓, downregulation of phosphorylated Rb and cyclin D,
cycD1/CCND1↓,
Dose∅, Interestingly, cell migration was somewhat increased with 10 μM accompanied by up-regulation of tNOX expression
β-catenin/ZEB1↓,
N-cadherin↓,
E-cadherin↑,

5894-

CAR,

Targeting Gastrointestinal Cancers with Carvacrol: Mechanistic Insights and Therapeutic Potential

Review,

Var,

AntiCan↑, Carvacrol has demonstrated strong anticancer properties by modulating multiple molecular pathways governing apoptosis, inflammation, angiogenesis, and metastasis.
Apoptosis↑,
Inflam↓,
angioG↓,
TumMeta↓,
selectivity↑, revealed its ability to selectively target cancer cells while sparing healthy tissue
BioAv↑, nanotechnology have further enhanced its pharmacological profile by improving solubility, stability, and tumor-targeted delivery.
ChemoSen↑, synergistic effects when used in combination with conventional chemotherapeutics.
Dose↝, 84.38% of OEO’s contents are ‘carvacrol’.
TumCP↓, limit metastasis, induce apoptosis, suppress tumor cell proliferation, and improve the effectiveness of traditional chemotherapy medications
hepatoP↑, Carvacrol shows biological activities, such as antimicrobial, antitumor, antimutagenic, antigenotoxic, anti-inflammatory, anti-angiogenic, hepatoprotective, and antihepatotoxic properties.
Casp3↑, induced apoptosis by activating caspase-3 and caspase-9 while downregulating Bcl-2 mRNA levels
Casp9↑,
Bcl-2↓,
ROS↑, carvacrol causes oxidative stress by increasing the production of reactive oxygen species (ROS) and depleting GSH levels, which results in strong lethal effects on AGS gastric cancer
GSH↓,
BAX↑, upregulating pro-apoptotic markers such as Bax, caspase-3, caspase-7, caspase-8, caspase-9, cytochrome C, Fas, Fas-associated death domain (FADD), and p53
Casp7↑,
Casp8↑,
Cyt‑c↑,
Fas↑,
FADD↑,
P53↑,
Bcl-2↓, downregulating anti-apoptotic Bcl-2.
TumMeta↓, preventing metastasis by limiting the migration and invasion of cancer cells by upregulating epithelial markers like E-Cadherin and tissue inhibitors of metalloproteinases 2 and 3 (TIMP2 and TIMP3)
TumCMig↓,
TumCI↓,
E-cadherin↑,
TIMP2↑,
TIMP3↑,
N-cadherin↓, downregulating mesenchymal markers like N-Cadherin and ZEB2
ZEB2↓,
*lipid-P↓, protects the liver from diethylnitrosamine (DEN)-induced hepatocellular carcinogenesis by reducing lipid peroxidation, restoring key liver enzymes (AST, ALT, ALP, LDH, cGT)
*AST↓,
*ALAT↓,
*ALP↓,
*LDH↓,
*SOD↑, and enhancing antioxidant defenses (SOD, CAT, GPx, GR, GSH)
*Catalase↑,
*GPx↑,
*GSR↑,
selectivity↑, while selectively inducing apoptosis in cancer cells without harming normal liver tissue
cl‑PARP↑, inhibits HepG2 cancer cell growth by activating caspase-3, promoting PARP cleavage, downregulating Bcl-2, and modulating the MAPK signaling pathway by selectively reducing ERK1/2 phosphorylation while activating p38
ERK↓,
p38↑,
OS↑, rats (aged 6–8 weeks) demonstrated that carvacrol enhances sorafenib efficacy in HCC, improving survival rates, reducing tumor progression, and mitigating sorafenib-induced cardiac and hepatic toxicity.
AFP↓, carvacrol reduces serum alpha-fetoprotein (AFP) and alpha-L-fucosidase (AFU) levels by downregulating COX-2 and oxidative stress, inhibits angiogenesis via VEGF suppression,
COX2↓,
VEGF↓,
PCNA↓, prevents tumor proliferation by downregulating proliferating cell nuclear antigen (PCNA) and Ki-67 through TNF-α suppression.
Ki-67↓,
TNF-α↓,
BioAv↓, Despite carvacrol’s promising effects in vitro and in vivo, limitations such as bioavailability and solubility challenge its therapeutic application.

1104-

CAR,

Carvacrol Ameliorates Transforming Growth Factor-β1-Induced Extracellular Matrix Deposition and Reduces Epithelial-Mesenchymal Transition by Regulating The Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway In Hk-2 Cells

in-vitro,

Kidney,

HK-2

tumCV↓,
COL4↓,
COL1↓,
Fibronectin↓,
E-cadherin↑, attenuated (TGF-β1-induced) decrease of E-cadherin
Snail↑,
Vim↑,
α-SMA↑,
PI3K↓,
Akt↓,

1103-

CBD,

Cannabidiol inhibits invasion and metastasis in colorectal cancer cells by reversing epithelial-mesenchymal transition through the Wnt/β-catenin signaling pathway

vitro+vivo,

NA,

Apoptosis↑,
TumCP↓,
TumCMig↓,
TumMeta↓,
EMT↓,
E-cadherin↑,
N-cadherin↓,
Snail↓,
Vim↓,
Hif1a↓,
Wnt/(β-catenin)↓,
AXIN1↑,
TumVol↓, orthotopic xenograft tumors
TumW↓,

6002-

CGA,

Chlorogenic Acid: A Systematic Review on the Biological Functions, Mechanistic Actions, and Therapeutic Potentials

Review,

Var,

Review,

Diabetic,

Review,

AD,

Review,

Park,

Review,

Stroke,

*neuroP↑, including neuroprotection for neurodegenerative disorders and diabetic peripheral neuropathy, anti-inflammation, anti-oxidation, anti-pathogens, mitigation of cardiovascular disorders,
*Inflam↓,
*antiOx↑,
*cardioP↑, Cardiovascular Protective Effect
*NRF2↑, pivotal antioxidants by activating the Nrf2 pathway
*AMPK↑, It elevates AMPK pathways for the maintenance and restoration of metabolic homeostasis of glucose and lipids.
*SOD↑, figure1
*Catalase↑,
*GSH↑,
*GPx↑,
*ROS↓,
*TNF-α↓,
*IL6↓,
*NF-kB↓,
*COX2↓,
*glucose↓, CGA can attenuate glucose absorption
*TRPC1↓, CGA suppresses the levels of transient receptor potential canonical channel 1 (TRPC1) and decreases ROS and Ca2+, thus mitigating lysophosphatidylcholine (LPC)-induced endothelial injuries
*Ca+2↓,
*HO-1↑, enhancing superoxide dismutase (SOD), and producing NO and heme oxygenase (HO)-1
*NF-kB↓, CGAs can regulate NF-κB and PPARα pathways, lower HIF-1α expression, and suppress cardiac apoptotic signaling, thus executing beneficial effects against cardiac hypertrophy
*PPARα↝,
*Hif1a↓,
*JNK↓, CGA can inhibit NF-κB and JNK pathways, exhibiting cardioprotection
*BP↓, GCE (93 or 185 mg for 4 weeks) could lead to a reduction of 4.7 and 5.6 mmHg in levels of systolic blood pressure (SBP) and a decrease of 3.3 and 3.9 mmHg in levels of diastolic blood pressure (DBP)
*AntiDiabetic↑, CGA has shown its functions in protecting β cells from apoptosis, improving β cell function, facilitating glycemic control, and mitigating DM complications.
*hepatoP↑, CGA can mediate hepatoprotective roles in various pathological conditions of the liver via antioxidant and anti-inflammatory features
*TLR4↓, (1) It can inhibit TLR4-mediated activation of NF-κB, thus suppressing pro-inflammatory responses;
*NRF2↑, (3) it can increase the activity of the Nrf2 pathway
*Casp↓, (4) it can inhibit caspases’ activation to suppress hepatic apoptosis induced by chemicals or toxins.
*neuroP↑, CGA has shown diverse neuroprotective effects on various neuropathological conditions which may be exerted through inhibition of neuroinflammation, reduction in ROS production, prevention of oxidation, and suppression of neuronal apoptosis
*Aβ↓, CGA or extracts containing CGA can inhibit Aβ aggregation-caused cellular injury in SH-SY5Y cells, a neuroblastoma cell line
*LDH↓, CGA increases survival and decreases apoptosis via decreasing activities of lactate dehydrogenase (LDH) and the levels of MDA and raising the levels of SOD and GSH-Px
*MDA↓,
*memory↑, CGA prevents Aβ deposition and neuronal loss and ameliorates learning and memory deterioration in APP/PS2 mice
*AChE↓, CGA inhibits acetylcholinesterase (AChE) activity in rat brains, suggesting its beneficial effect against cognitive impairment
*eff↑, CGA protects against injury caused by cerebral ischemia/reperfusion
EMT↝, It also modulates the epithelial–mesenchymal transition (EMT) process of breast cancer cells by downregulation of N-cadherin and upregulation of E-cadherin
N-cadherin↓,
E-cadherin↑,
TumCCA↑, CGA can stall the cells in the S phase and cause DNA injury in human colon cancer cell lines such as HCT116 and HT29 by increasing ROS production, upregulation of phosphorylated p53, HO-1, and Nrf2
ROS↑,
p‑P53↑,
HO-1↑,
NRF2↑,
ChemoSen↑, CGA in combination with doxorubicin suppresses cellular metabolic activity, colony formation, and cell growth of U2OS and MG-63 cells by upregulating caspase-3 and PARP and suppressing the p44/42 MAPK pathway, thus inducing apoptosis
mtDam↑, mechanism involves CGA-mediated excessive ROS production, causing mitochondrial dysfunction, leading to increases in cleaved levels of caspase-3, caspase-9, PARP, and Bax/Bcl-2 ratio
Casp3↑,
Casp9↑,
PARP↑,
Bax:Bcl2↑,
TumCG↓, in vivo experiments showing that CGA can reduce tumor growth and volume in pancreatic cancer cell-bearing nude mice by modifying cancer cell metabolism through decreasing levels of cyclin D1, c-Myc, and cyclin-dependent kinase-2 (CDK-2),
cycD1/CCND1↓,
cMyc↓,
CDK2↓,
mitResp↓, interrupting mitochondrial respiration, and suppressing aerobic glycolysis
Glycolysis↓,
Hif1a↓, CGA arrests cells at the phase of G1 and inhibits cell viability of prostate cancer cell DU145 by suppressing the levels of HIF-1α and SPHK-1, PCNA, cyclin-D, CDK-4, p-Akt, p-GSK-3β, and VEGF
PCNA↓,
p‑GSK‐3β↓,
VEGF↓,
PI3K↓, inhibition of the PI3K/Akt/mTOR pathway
Akt↓,
mTOR↓,
OS↑, Extending Lifespan in Worms

1106-

CGA,

Chlorogenic Acid Inhibits Epithelial-Mesenchymal Transition and Invasion of Breast Cancer by Down-Regulating LRP6

vitro+vivo,

BC,

MCF-7

E-cadherin↑,
ZO-1↑,
Zeb1↓,
N-cadherin↓,
Vim↓,
Snail↓,
Slug↓,
MMP2↓,
MMP9↓,
TumCMig↓,
TumCI↓,
LRP6↓,
p‑LRP6↓,
β-catenin/ZEB1↓,
TumVol↓, in vivo
TumW↓,

2782-

CHr,

Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives

Review,

Var,

Review,

Stroke,

Review,

Park,

*antiOx↑, antioxidant, anti-inflammatory, hepatoprotective, neuroprotective
*Inflam↓, inhibitory effect of chrysin on inflammation and oxidative stress is also important in Parkinson’s disease
*hepatoP↑,
*neuroP↑,
*BioAv↓, Accumulating data demonstrates that poor absorption, rapid metabolism, and systemic elimination are responsible for poor bioavailability of chrysin in humans that, subsequently, restrict its therapeutic effects
*cardioP↑, cardioprotective [69], lipid-lowering effect [70]
*lipidLev↓,
*RenoP↑, Renoprotective
*TNF-α↓, chrysin reduces levels of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2).
*IL2↓,
*PI3K↓, induction of the PI3K/Akt signaling pathway by chrysin contributes to a reduction in oxidative stress and inflammation during cerebral I/R injury
*Akt↓,
*ROS↓,
*cognitive↑, Chrysin (25, 50, and 100 mg/kg) improves cognitive capacity, inflammation, and apoptosis to ameliorate traumatic brain injury
eff↑, chrysin and silibinin is beneficial in suppressing breast cancer malignancy via decreasing cancer proliferation
cycD1/CCND1↓, chrysin and silibinin induced cell cycle arrest via down-regulation of cyclin D1 and hTERT
hTERT/TERT↓,
VEGF↓, Administration of chrysin is associated with the disruption of hypoxia-induced VEGF gene expression
p‑STAT3↓, chrysin is capable of reducing STAT3 phosphorylation in hypoxic conditions without affecting the HIF-1α protein level.
TumMeta↓, chrysin is a potent agent in suppressing metastasis and proliferation of breast cancer cells during hypoxic conditions
TumCP↓,
eff↑, combination therapy of breast cancer cells using chrysin and metformin exerts a synergistic effect and is more efficient compared to chrysin alone
eff↑, combination of quercetin and chrysin reduced levels of pro-inflammatory factors, such as IL-1β, Il-6, TNF-α, and IL-10, via NF-κB down-regulation.
IL1β↓,
IL6↓,
NF-kB↓,
ROS↑, after chrysin administration, an increase occurs in levels of ROS that, subsequently, impairs the integrity of the mitochondrial membrane, leading to cytochrome C release and apoptosis induction
MMP↓,
Cyt‑c↑,
Apoptosis↑,
ER Stress↑, in addition to mitochondria, ER can also participate in apoptosis
Ca+2↑, Upon chrysin administration, an increase occurs in levels of ROS and cytoplasmic Ca2+ that mediate apoptosis induction in OC cells
TET1↑, In MKN45 cells, chrysin promotes the expression of TET1
Let-7↑, Chrysin is capable of promoting the expression of miR-9 and Let-7a as onco-suppressor factors in cancer to inhibit the proliferation of GC cells
Twist↓, Down-regulation of NF-κB, and subsequent decrease in Twist/EMT are mediated by chrysin administration, negatively affecting cervical cancer metastasis
EMT↓,
TumCCA↑, nduction of cell cycle arrest and apoptosis via up-regulation of caspase-3, caspase-9, and Bax are mediated by chrysin
Casp3↑,
Casp9↑,
BAX↑,
HK2↓, Chrysin administration (15, 30, and 60 mM) reduces the expression of HK-2 in hepatocellular carcinoma (HCC) cells to impair glucose uptake and lactate production.
GlucoseCon↓,
lactateProd↓,
Glycolysis↓, In addition to glycolysis metabolism impairment, the inhibitory effect of chrysin on HK-2 leads to apoptosis
SHP1↑, upstream modulator of STAT3 known as SHP-1 is up-regulated by chrysin
N-cadherin↓, Furthermore, N-cadherin and E-cadherin are respectively down-regulated and up-regulated upon chrysin administration in inhibiting melanoma invasion
E-cadherin↑,
UPR↑, chrysin substantially diminishes survival by ER stress induction via stimulating UPR, PERK, ATF4, and elF2α
PERK↑,
ATF4↑,
eIF2α↑,
RadioS↑, Irradiation combined with chrysin exerts a synergistic effect
NOTCH1↑, Irradiation combined with chrysin exerts a synergistic effect
NRF2↓, in reducing Nrf2 expression, chrysin down-regulates the expression of ERK and PI3K/Akt pathways—leading to an increase in the efficiency of doxorubicin in chemotherapy
BioAv↑, chrysin at the tumor site by polymeric nanoparticles leads to enhanced anti-tumor activity, due to enhanced cellular uptake
eff↑, Chrysin- and curcumin-loaded nanoparticles significantly promote the expression of TIMP-1 and TIMP-2 to exert a reduction in melanoma invasion

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↑, 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↓, 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.

2785-

CHr,

Emerging cellular and molecular mechanisms underlying anticancer indications of chrysin

Review,

Var,

*NF-kB↓, suppressed pro-inflammatory cytokine expression and histamine release, downregulated nuclear factor kappa B (NF-kB), cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS)
*COX2↓,
*iNOS↓,
angioG↓, upregulated apoptotic pathways [28], inhibited angiogenesis [29] and metastasis formation
TOP1↓, suppressed DNA topoisomerases [31] and histone deacetylase [32], downregulated tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β)
HDAC↓,
TNF-α↓,
IL1β↓,
cardioP↑, promoted protective signaling pathways in the heart [34], kidney [35] and brain [8], decreased cholesterol level
RenoP↑,
neuroP↑,
LDL↓,
BioAv↑, bioavailability of chrysin in the oral route of administration was appraised to be 0.003–0.02% [55], the maximum plasma concentration—12–64 nM
eff↑, Chrysin alone and potentially in combination with metformin decreased cyclin D1 and hTERT gene expression in the T47D breast cancer cell line
cycD1/CCND1↓,
hTERT/TERT↓,
MMP-10↓, Chrysin pretreatment inhibited MMP-10 and Akt signaling pathways
Akt↓,
STAT3↓, Chrysin declined hypoxic survival, inhibited activation of STAT3, and reduced VEGF expression in hypoxic cancer cells
VEGF↓,
EGFR↓, chrysin to inhibit EGFR was reported in a breast cancer stem cell model [
Snail↓, chrysin downregulated MMP-10, reduced snail, slug, and vimentin expressions increased E-cadherin expression, and inhibited Akt signaling pathway in TNBC cells, proposing that chrysin possessed a reversal activity on EMT
Slug↓,
Vim↓,
E-cadherin↑,
eff↑, Fabrication of chrysin-attached to silver and gold nanoparticles crossbred reduced graphene oxide nanocomposites led to augmentation of the generation of ROS-induced apoptosis in breast cancer
TET1↑, Chrysin induced augmentation in TET1
ROS↑, Pretreatment with chrysin induced ROS formation, and consecutively, inhibited Akt phosphorylation and mTOR.
mTOR↓,
PPARα↓, Chrysin inhibited mRNA expression of PPARα
ER Stress↑, ROS production by chrysin was the critical mediator behind induction of ER stress, leading to JNK phosphorylation, intracellular Ca2+ release, and activation of the mitochondrial apoptosis pathway
Ca+2↑,
ERK↓, reduced protein expression of p-ERK/ERK
MMP↑, Chrysin pretreatment led to an increase in mitochondrial ROS creation, swelling in isolated mitochondria from hepatocytes, collapse in MMP, and release cytochrome c.
Cyt‑c↑,
Casp3↑, Chrysin could elevate caspase-3 activity in the HCC rats group
HK2↓, chrysin declined HK-2 combined with VDAC-1 on mitochondria
NRF2↓, chrysin inhibited the Nrf2 expression and its downstream genes comprising AKR1B10, HO-1, and MRP5 by quenching ERK and PI3K-Akt pathway
HO-1↓,
MMP2↓, Chrysin pretreatment also downregulated MMP2, MMP9, fibronectin, and snail expression
MMP9↓,
Fibronectin↓,
GRP78/BiP↑, chrysin induced GRP78 overexpression, spliced XBP-1, and eIF2-α phosphorylation
XBP-1↓,
p‑eIF2α↑,
*AST↓, Chrysin administration significantly reduced AST, ALT, ALP, LDH and γGT serum activities
ALAT↓,
ALP↓,
LDH↓,
COX2↑, chrysin attenuated COX-2 and NFkB p65 expression, and Bcl-xL and β-arrestin levels
Bcl-xL↓,
IL6↓, Reduction in IL-6 and TNF-α and augmentation in caspases-9 and 3 were observed due to chrysin supplementation.
PGE2↓, Chrysin induced entire suppression NF-kB, COX-2, PG-E2, iNOS as well.
iNOS↓,
DNAdam↑, Chrysin induced apoptosis of cells by causing DNA fragmentation and increasing the proportions of DU145 and PC-3 cells
UPR↑, Also, it induced ER stress via activation of UPR proteins comprising PERK, eIF2α, and GRP78 in DU145 and PC-3 cells.
Hif1a↓, Chrysin increased the ubiquitination and degradation of HIF-1α by increasing its prolyl hydroxylation
EMT↓, chrysin was effective in HeLa cell by inhibiting EMT and CSLC properties, NF-κBp65, and Twist1 expression
Twist↓,
lipid-P↑, Chrysin disrupted intracellular homeostasis by altering MMP, cytosolic Ca (2+) levels, ROS generation, and lipid peroxidation, which plays a role in the death of choriocarcinoma cells.
CLDN1↓, Chrysin decreased CLDN1 and CLDN11 expression in human lung SCC
PDK1↓, Chrysin alleviated p-Akt and inhibited PDK1 and Akt
IL10↓, Chrysin inhibited cytokines release, TNF-α, IL-1β, IL-10, and IL-6 induced by Ni in A549 cells.
TLR4↓, Chrysin suppressed TLR4 and Myd88 mRNA and protein expression.
NOTCH1↑, Chrysin inhibited tumor growth in ATC both in vitro and in vivo through inducing Notch1
PARP↑, Pretreating cells with chrysin increased cleaved PARP, cleaved caspase-3, and declined cyclin D1, Mcl-1, and XIAP.
Mcl-1↓,
XIAP↓,

1107-

CHr,

Chrysin inhibits metastatic potential of human triple-negative breast cancer cells by modulating matrix metalloproteinase-10, epithelial to mesenchymal transition, and PI3K/Akt signaling pathway

in-vitro,

BC,

(5, 10 and 20 μM

TumCP↓,
Apoptosis↑,
MMP-10↓,
E-cadherin↑,
Vim↓,
Snail↓,
Slug↓,
EMT↓, reversal effect on epithelial-mesenchymal transition

1587-

Citrate,

ATP citrate lyase: A central metabolic enzyme in cancer

Review,

NA,

ACLY↓, administration of citrate at high level mimics a strong inhibition of ACLY and could be tested to strengthen the effects of current therapies. -a strong ACLY inhibition could be mimicked by by flooding the cytosol with citrate.
other↓, ACLY inhibition by simple drugs such as HCA or bempedoic acid should be tested, optimally associated with glycolytic inhibitors (or glucose starvation diet) and current therapies.
PFK1↓, citrate promotes: - the inactivation of PFK1 and decreases ATP production [
ATP↓,
PFK2↓, inhibition of PFK2 in ascite cancer cells
Mcl-1↓, deactivation of the anti-apoptotic factor Mcl-1 and the activation of caspases such as caspase 2, 3 and 9
Casp3↑,
Casp2↑,
Casp9↑,
IGF-1R↓, downregulation of the IGF-1R/PI3K/AKT
PI3K↓,
Akt↓,
p‑Akt↓, decreased phosphorylation of AKT and ERK in non-small cell lung cancer
p‑ERK↓,
PTEN↑, activation of PTEN suppressor,
Snail↓, reversion of dedifferentiation (in particular through Snail inhibition with E-cadherin expression) and stimulation of T lymphocytes response
E-cadherin↑,
ChemoSen↑, increasing the sensitivity of tumors to cisplatin

16-

CP,

RES,

Resveratrol inhibits the hedgehog signaling pathway and epithelial-mesenchymal transition and suppresses gastric cancer invasion and metastasis

in-vitro,

GC,

SGC-7901

HH↓, decrease in Gli-1, Snail and N-cadherin expression, and an increase in E-cadherin expression in the resveratrol and cyclopamine group compared
Gli1↓,
EMT↓, suggesting that resveratrol inhibited the Hh pathway and EMT, as did cyclopamine.
N-cadherin↓,
E-cadherin↑,
Snail↓,
TumCI↓, suppress invasion and metastasis in gastric cancer in vitro.
TumMeta↓, Resveratrol and cyclopamine inhibits the metastasis and invasion of SGC-7901 cells

11-

CUR,

Curcumin inhibits hypoxia-induced epithelial‑mesenchymal transition in pancreatic cancer cells via suppression of the hedgehog signaling pathway

in-vitro,

PC,

PANC1

HH↓, suppression of the hedgehog signaling pathway
Shh↓, Curcumin significantly decreased hypoxia-induced expression levels of SHH, SMO and GLI1.
Smo↓,
Gli1↓,
N-cadherin↓,
E-cadherin↑,
Vim↓,
TumCP↓, inhibit the hypoxia-induced cell proliferation, migration and invasion in pancreatic cancer,
TumCMig↓,
TumCI↓,
EMT↓, mediate the expression of EMT-related factors.
chemoPv↑, Curcumin might be a potential candidate for chemoprevention of this severe disease.

473-

CUR,

Curcumin inhibits epithelial-mesenchymal transition in oral cancer cells via c-Met blockade

in-vitro,

Oral,

HSC4

15 μM, 48 h

in-vitro,

Oral,

Ca9-22

Vim↓,
p‑cMET↓,
p‑ERK↓,
pro‑MMP9↓,
E-cadherin↑,

470-

CUR,

Regulation of carcinogenesis and modulation through Wnt/β-catenin signaling by curcumin in an ovarian cancer cell line

in-vitro,

Ovarian,

SKOV3

20 μM, 96 h

Wnt/(β-catenin)↓,
EMT↓,
DNMT3A↓,
cycD1/CCND1↓,
cMyc↓,
Fibronectin↓,
Vim↓,
E-cadherin↑,
SFRP5↑,

464-

CUR,

Curcumin inhibits the viability, migration and invasion of papillary thyroid cancer cells by regulating the miR-301a-3p/STAT3 axis

in-vitro,

Thyroid,

BCPAP

2.5, 5, 10, 20 and 40 µM, 24 h

in-vitro,

Thyroid,

TPC-1

TumCI↓,
TumCI↓,
MMP2↓,
MMP9↓,
EMT↓,
STAT3↓,
miR-301a-3p↓,
STAT↓,
N-cadherin↓,
Vim↓,
Fibronectin↓,
p‑JAK↓,
p‑JAK2↓,
p‑JAK3↓,
p‑STAT1↓,
p‑STAT2↓,
E-cadherin↑,

Showing Research Papers: 1 to 50 of 158
Page 1 of 4 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 158

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 4, Catalase↑, 3, GPx↑, 2, GSH↑, 1, GSR↑, 1, GSTs↑, 1, HDL↑, 1, HO-1↑, 1, lipid-P↓, 1, MDA↓, 1, NRF2↑, 2, ROS↓, 3, SOD↑, 3,

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1, AMPK↑, 1, glucose↓, 1, LDH↓, 2, lipidLev↓, 1, PPARα↝, 1,

Cell Death ⓘ

Akt↓, 1, Casp↓, 1, iNOS↓, 1, JNK↓, 1, MAPK↓, 2,

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 2, p‑ERK↓, 1, PI3K↓, 1, PTEN↑, 1,

Migration ⓘ

Ca+2↓, 1, Ca+2↝, 1, cal2↓, 1, COL1↓, 1, E-cadherin↑, 3, F-actin↓, 1, N-cadherin↓, 1, PKCδ↓, 1, Smad7↑, 1, Snail↓, 1, TGF-β1↓, 1, TRPC1↓, 1, TumCMig↓, 1, Vim↓, 3, ZO-1↑, 1, α-SMA↓, 2, β-catenin/ZEB1↓, 1,

Angiogenesis & Vasculature ⓘ

Hif1a↓, 1, VEGF↑, 1,

Immune & Inflammatory Signaling ⓘ

COX2↓, 2, IL2↓, 1, IL6↓, 1, Inflam↓, 5, NF-kB↓, 4, TLR4↓, 1, TNF-α↓, 2,

Synaptic & Neurotransmission ⓘ

AChE↓, 1,

Protein Aggregation ⓘ

Aβ↓, 1,

Drug Metabolism & Resistance ⓘ

BioAv↓, 2, eff↑, 1, P450↓, 1,

Clinical Biomarkers ⓘ

ALAT↓, 1, ALP↓, 1, AST↓, 2, BP↓, 1, IL6↓, 1, LDH↓, 2,

Functional Outcomes ⓘ

AntiDiabetic↑, 1, cardioP↑, 2, cognitive↑, 1, hepatoP↑, 2, memory↑, 1, neuroP↑, 3, RenoP↑, 1, toxicity↝, 1,
Total Targets: 73

Scientific Paper Hit Count for: E-cadherin, E-cadherin

13 Curcumin
8 Resveratrol
6 Luteolin
6 Pterostilbene
6 Quercetin
5 Fisetin
5 Honokiol
5 Sulforaphane (mainly Broccoli)
5 Thymoquinone
4 Astragalus
4 Apigenin (mainly Parsley)
4 Artemisinin
4 Chrysin
4 Silymarin (Milk Thistle) silibinin
3 Baicalein
3 Magnolol
3 Rosmarinic acid
3 Urolithin
2 Allicin (mainly Garlic)
2 Cisplatin
2 Baicalin
2 Berberine
2 Betulinic acid
2 Boron
2 Propolis -bee glue
2 Capsaicin
2 Carvacrol
2 Chlorogenic acid
2 Citric Acid
2 Ellagic acid
2 Garcinol
2 Grapeseed extract
2 Juglone
2 Piperine
2 Piperlongumine
2 Shikonin
2 Selenite (Sodium)
2 Ursolic acid
2 Vitamin D3
2 VitK3,menadione
1 Alpha-Lipoic-Acid
1 Aspirin -acetylsalicylic acid
1 Astaxanthin
1 Biochanin A
1 Boswellia (frankincense)
1 brusatol
1 Butyrate
1 Caffeic acid
1 Cannabidiol
1 Cyclopamine
1 Oxaliplatin
1 diet FMD Fasting Mimicking Diet
1 Emodin
1 Shilajit/Fulvic Acid
1 Galloflavin
1 Paclitaxel
1 Ginkgo biloba
1 Proanthocyanidins
1 Hydroxycinnamic-acid
1 HydroxyTyrosol
1 Laetrile B17 Amygdalin
1 Lycopene
1 5-fluorouracil
1 Melatonin
1 Metformin
1 Oroxylin A
1 Oleuropein
1 Phenylbutyrate
1 Phenethyl isothiocyanate
1 Docetaxel
1 salinomycin
1 statins
1 Taurine
1 Vitamin C (Ascorbic Acid)

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#:89  State#:%  Dir#:2
  wNotes=on  sortOrder:rid,rpid

E-cadherin Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Metal & Cofactor Biology ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Immune & Inflammatory Signaling ⓘ

Synaptic & Neurotransmission ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

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