Snail Cancer Research Results

Snail, Snail: Click to Expand ⟱

Source:

Type:

Snail gene may show a role in recurrence of breast cancer by downregulating E-cadherin and inducing an epithelial to mesenchymal transition. Snail promotes metastasis of breast cancer cells and overexpression of Snail is a biomarker of poor clinical outcome for patients with breast cancer.
Snail, a repressor of E-cadherin and an inducer of EMT.
Snail (SNAI1):
A transcription factor that plays a key role in the regulation of the epithelial-to-mesenchymal transition (EMT).
It suppresses the expression of epithelial markers (such as E-cadherin) and upregulates mesenchymal markers, facilitating changes in cell adhesion and motility.
EMT Induction:
Snail actively represses genes such as E-cadherin, a protein critical for cell–cell adhesion. Its upregulation leads to a loss of epithelial characteristics and the acquisition of a mesenchymal phenotype, enhancing migratory potential.
Invasion and Metastasis:
Through EMT induction, Snail facilitates tumor cell dissemination and invasion into surrounding tissues, thereby playing a central role in metastasis.

Elevated levels of Snail have been observed in a variety of cancers, including breast, colorectal, pancreatic, and head and neck cancers.
Elevated Snail expression is frequently associated with a worse prognosis, including lower overall survival rates and increased likelihood of metastasis.

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↓,

278-

ALA,

The Multifaceted Role of Alpha-Lipoic Acid in Cancer Prevention, Occurrence, and Treatment

Review,

NA,

ROS↑, direct anticancer effect of the antioxidant ALA is manifested as an increase in intracellular ROS levels in cancer cells
NRF2↑, enhance the activity of the anti-inflammatory protein nuclear factor erythroid 2–related factor 2 (Nrf2), thereby reducing tissue damage
Inflam↓,
frataxin↑,
*BioAv↓, Oral ALA has a bioavailability of approximately 30% due to issues such as poor stability in the stomach, low solubility, and hepatic degradation.
ChemoSen↑, ALA can enhance the functionality of various other anticancer drugs, including 5-fluorouracil in colon cancer cells and cisplatin in MCF-7 breast cancer cells
Hif1a↓, it is inferred that lipoic acid may inhibit the expression of HIF-1α
eff↑, act as a synergistic agent with natural polyphenolic substances such as apigenin and genistein
FAK↓, ALA inhibits FAK activation by downregulating β1-integrin expression and reduces the levels of MMP-9 and MMP-2
ITGB1↓,
MMP2↓,
MMP9↓,
EMT↓, ALA inhibits the expression of EMT markers, including Snail, vimentin, and Zeb1
Snail↓,
Vim↓,
Zeb1↓,
P53↑, ALA also stimulates the mutant p53 protein and depletes MGMT
MGMT↓, depletes MGMT by inhibiting NF-κB signalling, thereby inducing apoptosis
Mcl-1↓,
Bcl-xL↓,
Bcl-2↓,
survivin↓,
Casp3↑,
Casp9↑,
BAX↑,
p‑Akt↓, ALA inhibits the activation of tumour stem cells by reducing Akt phosphorylation.
GSK‐3β↓, phosphorylation and inactivation of GSK3β
*antiOx↑, indirect antioxidant protection through metal chelation (ALA primarily binds Cu2+ and Zn2+, while DHLA can bind Cu2+, Zn2+, Pb2+, Hg2+, and Fe3+) and the regeneration of certain endogenous antioxidants, such as vitamin E, vitamin C, and glutathione
*ROS↓, ALA can directly quench various reactive species, including ROS, reactive nitrogen species, hydroxyl radicals (HO•), hypochlorous acid (HclO), and singlet oxygen (1O2);
selectivity↑, In normal cells, ALA acts as an antioxidant by clearing ROS. However, in cancer cells, it can exert pro-oxidative effects, inducing pathways that restrict cancer progression.
angioG↓, Combining these two hypotheses, it can be hypothesized that ALA may regulate copper and HIF-2α to limit tumor angiogenesis.
MMPs↓, ALA was shown to inhibit invasion by decreasing the mRNA levels of key matrix metalloproteinases (MMPs), specifically MMP2 and MMP9, which are crucial for the metastatic process
NF-kB↓, ALA has been shown to enhance the efficacy of the chemotherapeutic drug paclitaxel in breast and lung cancer cells by inhibiting the NF-κB signalling pathway and the functions of integrin β1/β3 [138,139]
ITGB3↓,
NADPH↓, ALA has been shown to inhibit NADPH oxidase, a key enzyme closely associated with NP, including NOX4

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

1560-

Api,

Apigenin as an anticancer agent

Review,

NA,

Apoptosis↑,
Casp3∅,
Casp8∅,
TNF-α∅,
Cyt‑c↑, evidenced by the induction of cytochrome c
MMP2↓, Apigenin treatment leads to significant downregulation of matrix metallopeptidases-2, -9, Snail, and Slug,
MMP9↓,
Snail↓,
Slug↓,
NF-kB↓, NF-κB p105/p50, PI3K, Akt, and the phosphorylation of p-Akt decreases after treatment
p50↓,
PI3K↓,
Akt↓,
p‑Akt↓,

1095-

Api,

Apigenin inhibits epithelial-mesenchymal transition of human colon cancer cells through NF-κB/Snail signaling pathway

Analysis,

Colon,

Snail↓, Snail inhibitor apigenin
EMT↓,
NF-kB↓,

581-

Api,

Cisplatin,

The natural flavonoid apigenin sensitizes human CD44+ prostate cancer stem cells to cisplatin therapy

in-vitro,

Pca,

CD44+

15uM / 7.5uM for 48

CD44+PCa

Bcl-2↓,
survivin↓,
Casp8↑,
P53↑,
Sharpin↓,
APAF1↑,
p‑Akt↓,
NF-kB↓,
P21↑,
Cyc↓,
CDK2↓,
CDK4/6↓,
Snail↓,
ChemoSen↑, Apigenin significantly increased the inhibitory effects of cisplatin on cell migration via downregulation of Snail expression

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↓,

240-

Api,

The flavonoid apigenin reduces prostate cancer CD44(+) stem cell survival and migration through PI3K/Akt/NF-κB signaling

in-vitro,

Pca,

PC3

 25 uM

in-vitro,

Pca,

CD44+

P21↑,
p27↑,
Casp3↑,
Casp8↑,
Slug↓,
Snail↓,
NF-kB↓,
PI3K↓,
Akt↓,

3160-

Ash,

Withaferin A: A Pleiotropic Anticancer Agent from the Indian Medicinal Plant Withania somnifera (L.) Dunal

Review,

Var,

TumCCA↑, withaferin A suppressed cell proliferation in prostate, ovarian, breast, gastric, leukemic, and melanoma cancer cells and osteosarcomas by stimulating the inhibition of the cell cycle at several stages, including G0/G1 [86], G2, and M phase
H3↑, via the upregulation of phosphorylated Aurora B, H3, p21, and Wee-1, and the downregulation of A2, B1, and E2 cyclins, Cdc2 (Tyr15), phosphorylated Chk1, and Chk2 in DU-145 and PC-3 prostate cancer cells.
P21↑,
cycA1/CCNA1↓,
CycB/CCNB1↓,
cycE/CCNE↓,
CDC2↓,
CHK1↓,
Chk2↓,
p38↑, nitiated cell death in the leukemia cells by increasing the expression of p38 mitogen-activated protein kinases (MAPK)
MAPK↑,
E6↓, educed the expression of human papillomavirus E6/E7 oncogenes in cervical cancer cells
E7↓,
P53↑, restored the p53 pathway causing the apoptosis of cervical cancer cells.
Akt↓, oral dose of 3–5 mg/kg withaferin A attenuated the activation of Akt and stimulated Forkhead Box-O3a (FOXO3a)-mediated prostate apoptotic response-4 (Par-4) activation,
FOXO3↑,
ROS↑, the generation of reactive oxygen species, histone H2AX phosphorylation, and mitochondrial membrane depolarization, indicating that withaferin A can cause the oxidative stress-mediated killing of oral cancer cells [
γH2AX↑,
MMP↓,
mitResp↓, withaferin A inhibited the expansion of MCF-7 and MDA-MB-231 human breast cancer cells by ROS production, owing to mitochondrial respiration inhibition
eff↑, combination treatment of withaferin A and hyperthermia induced the death of HeLa cells via a decrease in the mitochondrial transmembrane potential and the downregulation of the antiapoptotic protein myeloid-cell leukemia 1 (MCL-1)
TumCD↑,
Mcl-1↓,
ER Stress↑, . Withaferin A also attenuated the development of glioblastoma multiforme (GBM), both in vitro and in vivo, by inducing endoplasmic reticulum stress via activating the transcription factor 4-ATF3-C/EBP homologous protein (ATF4-ATF3-CHOP)
ATF4↑,
ATF3↑,
CHOP↑,
NOTCH↓, modulating the Notch-1 signaling pathway and the downregulation of Akt/NF-κB/Bcl-2 . withaferin A inhibited the Notch signaling pathway
NF-kB↓,
Bcl-2↓,
STAT3↓, Withaferin A also constitutively inhibited interleukin-6-induced phosphorylation of STAT3,
CDK1↓, lowering the levels of cyclin-dependent Cdk1, Cdc25C, and Cdc25B proteins,
β-catenin/ZEB1↓, downregulation of p-Akt expression, β-catenin, N-cadherin and epithelial to the mesenchymal transition (EMT) markers
N-cadherin↓,
EMT↓,
Cyt‑c↑, depolarization and production of ROS, which led to the release of cytochrome c into the cytosol,
eff↑, combinatorial effect of withaferin A and sulforaphane was also observed in MDA-MB-231 and MCF-7 breast cancer cells, with a dramatic reduction of the expression of the antiapoptotic protein Bcl-2 and an increase in the pro-apoptotic Bax level, thus p
CDK4↓, downregulates the levels of cyclin D1, CDK4, and pRB, and upregulates the levels of E2F mRNA and tumor suppressor p21, independently of p53
p‑RB1↓,
PARP↑, upregulation of Bax and cytochrome c, downregulation of Bcl-2, and activation of PARP, caspase-3, and caspase-9 cleavage
cl‑Casp3↑,
cl‑Casp9↑,
NRF2↑, withaferin A binding with Keap1 causes an increase in the nuclear factor erythroid 2-related factor 2 (Nrf2) protein levels, which in turn, regulates the expression of antioxidant proteins that can protect the cells from oxidative stress.
ER-α36↓, Decreased ER-α
LDHA↓, inhibited growth, LDHA activity, and apoptotic induction
lipid-P↑, induction of oxidative stress, increased lipid peroxidation,
AP-1↓, anti-inflammatory qualities of withaferin A are specifically attributed to its inhibition of pro-inflammatory molecules, α-2 macroglobulin, NF-κB, activator protein 1 (AP-1), and cyclooxygenase-2 (COX-2) inhibition,
COX2↓,
RenoP↑, showing strong evidence of the renoprotective potential of withaferin A due to its anti-inflammatory activity
PDGFR-BB↓, attenuating the BB-(PDGF-BB) platelet growth factor
SIRT3↑, by increasing the sirtuin3 (SIRT3) expression
MMP2↓, withaferin A inhibits matrix metalloproteinase-2 (MMP-2) and MMP-9,
MMP9↓,
NADPH↑, but also provokes mRNA stimulation for a set of antioxidant genes, such as NADPH quinone dehydrogenase 1 (NQO1), glutathione-disulfide reductase (GSR), Nrf2, heme oxygenase 1 (HMOX1),
NQO1↑,
GSR↑,
HO-1↑,
*SOD2↑, cardiac ischemia-reperfusion injury model. Withaferin A triggered the upregulation of superoxide dismutase SOD2, SOD3, and peroxiredoxin 1(Prdx-1).
*Prx↑,
*Casp3?, and ameliorated cardiomyocyte caspase-3 activity
eff↑, combination with doxorubicin (DOX), is also responsible for the excessive generation of ROS
Snail↓, inhibition of EMT markers, such as Snail, Slug, β-catenin, and vimentin.
Slug↓,
Vim↓,
CSCs↓, highly effective in eliminating cancer stem cells (CSC) that expressed cell surface markers, such as CD24, CD34, CD44, CD117, and Oct4 while downregulating Notch1, Hes1, and Hey1 genes;
HEY1↓,
MMPs↓, downregulate the expression of MMPs and VEGF, as well as reduce vimentin, N-cadherin cytoskeleton proteins,
VEGF↓,
uPA↓, and protease u-PA involved in the cancer cell metastasis
*toxicity↓, A was orally administered to Wistar rats at a dose of 2000 mg/kg/day and had no adverse effects on the animals
CDK2↓, downregulated the activation of Bcl-2, CDK2, and cyclin D1
CDK4↓, Another study also demonstrated the inhibition of Hsp90 by withaferin A in a pancreatic cancer cell line through the degradation of Akt, cyclin-dependent kinase 4 Cdk4,
HSP90↓,

5172-

Ash,

Withaferin-A suppress AKT induced tumor growth in colorectal cancer cells

Akt↓, WA, a natural compound, resulted in significant inhibition of AKT activity and led to the inhibition of cell proliferation, migration and invasion
TumCP↓,
TumCMig↓,
TumCI↓,
EMT↓, by downregulating the epithelial to mesenchymal transition (EMT) markers in CRC cells overexpressing AKT
Snail↓, Further, significant inhibition of some important EMT markers, i.e., Snail, Slug, β-catenin and vimentin, was observed in WA-treated human CRC cells overexpressing AKT
Slug↓,
β-catenin/ZEB1↓,
Vim↓,
angioG↓, Significant inhibition of micro-vessel formation and the length of vessels were evident in WA-treated tumors, which correlated with a low expression of the angiogenic marker RETIC

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.

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↓,

1392-

BBR,

Based on network pharmacology and experimental validation, berberine can inhibit the progression of gastric cancer by modulating oxidative stress

in-vitro,

GC,

AGS

2.5, 5, 10, 20, 40 µM

in-vitro,

GC,

MKN45

TumCG↓,
TumCMig↓,
ROS↑, intracellular
MDA↑, intracellular
SOD↓, intracellular
NRF2↓,
HO-1↓,
Hif1a↓,
EMT↓,
Snail↓,
Vim↓,

2719-

BetA,

Betulinic Acid Restricts Human Bladder Cancer Cell Proliferation In Vitro by Inducing Caspase-Dependent Cell Death and Cell Cycle Arrest, and Decreasing Metastatic Potential

in-vitro,

CRC,

T24/HTB-9

30 μg/mL BA for 48 h

in-vitro,

Bladder,

UMUC3

33.2 μg/mL

in-vitro,

Bladder,

5637

 28.5 μg/mL

TumCD↑, BA induced cell death in bladder cancer cells and that are accompanied by apoptosis, necrosis, and cell cycle arrest.
Apoptosis↑,
TumCCA↑,
CycB/CCNB1↓, BA decreased the expression of cell cycle regulators, such as cyclin B1, cyclin A, cyclin-dependent kinase (Cdk) 2, cell division cycle (Cdc) 2, and Cdc25c
cycA1/CCNA1↓,
CDK2↓,
CDC25↓,
mtDam↑, BA-induced apoptosis was associated with mitochondrial dysfunction that is caused by loss of mitochondrial membrane potential, which led to the activation of mitochondrial-mediated intrinsic pathway.
BAX↑, BA up-regulated the expression of Bcl-2-accociated X protein (Bax) and cleaved poly-ADP ribose polymerase (PARP), and subsequently activated caspase-3, -8, and -9.
cl‑PARP↑,
Casp3↑,
Casp8↑,
Casp9↑,
Snail↓, decreased the expression of Snail and Slug in T24 and 5637 cells, and matrix metalloproteinase (MMP)-9 in UMUC-3 cells.
Slug↓,
MMP9↓,
selectivity↑, Among the bladder cancer cell lines, 5637 cells were much more sensitive to BA than T24 or UMUC-3 cells under the same conditions. However, BA does not affect cell growth in normal cell lines including RAW 264.7
MMP↓, BA Induces Loss of Mitochondrial Membrane Potential (MMP, ΔΨm) in Human Bladder Cancer Cells
ROS∅, As a result, we found that BA did not affect intracellular ROS levels in all three bladder cancer cells. In addition, BA-induced cell viability inhibition was not restored by NAC pre-treatment
TumCMig↓, BA Decreases Migration and Invasion of Human Bladder Cancer Cells
TumCI↓,

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

1652-

CA,

Caffeic Acid and Diseases—Mechanisms of Action

Review,

Var,

Dose∅, Black chokeberries seem to be the most potent source of caffeic acid (645 mg/100 g of dry weight)
ROS⇅, Therefore, we will mention the antioxidant (and prooxidant) effects of caffeic acid only briefly
NF-kB↓, In HepG2 cells, caffeic acid (100 µM) inhibited the activity of NF-κB/IL-6/STAT3 signaling, which decreased the expression of VEGF
STAT3↓,
VEGF↓,
MMP9↓, inhibited another downstream product of NF-κB: matrix metalloproteinase 9 (MM-9), which promotes tumor invasiveness and metastases
HSP70/HSPA5↑, caffeic acid (20 μM) also decreased the expression of mortalin(mitochondrial 70 kDa heat shock protein),
AST↝, normalized levels of alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bile acid, total cholesterol, HDL and LD
ALAT↝,
ALP↝,
Hif1a↓,
IL6↓,
IGF-1R↓,
P21↑,
iNOS↓,
ERK↓,
Snail↓,
BID↑,
BAX↑,
Casp3↑,
Casp7↑,
Casp9↑,
cycD1/CCND1↓,
Vim↓,
β-catenin/ZEB1↓,
COX2↓,
ROS↑, the chelating ability of caffeic acid is also responsible for its occasional pro-oxidant ability. After chelating Cu2+, the Cu2+ can be reduced to Cu+. combination of caffeic acid and endogenous copper ions can result in oxidative damage

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↑,

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↓,

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↓,

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

433-

CUR,

Curcumin Inhibits the Migration and Invasion of Non-Small-Cell Lung Cancer Cells Through Radiation-Induced Suppression of Epithelial-Mesenchymal Transition and Soluble E-Cadherin Expression

in-vitro,

Lung,

A549

1, 2, 5, 10 and 20 μM, 24 and 48 h

E-cadherin↓,
Vim↓,
Slug↓,
N-cadherin↓,
Snail↓, N-cadherin and Snail expression showed a slight decrease after treatment with different concentrations of curcumin.
MMP9↓, Curcumin inhibited MMP9 expression
EMT↓, Curcumin inhibits NSCLC migration and invasion by suppressing radiation-induced EMT and sE-cad expression by decreasing MMP9 expression

443-

CUR,

Reduced Caudal Type Homeobox 2 (CDX2) Promoter Methylation Is Associated with Curcumin’s Suppressive Effects on Epithelial-Mesenchymal Transition in Colorectal Cancer Cells

in-vitro,

CRC,

SW480

DNMT1↓,
DNMT3A↓,
N-cadherin↓,
Vim↓,
Wnt↓, Wnt3a
Snail↓, Snail1
Twist↓,
β-catenin/ZEB1↓,
E-cadherin↑,
EMT↓, Curcumin incubation inhibited EMT
CDX2↓,

1607-

EA,

Exploring the Potential of Ellagic Acid in Gastrointestinal Cancer Prevention: Recent Advances and Future Directions

Review,

GC,

STAT3↓, EA inhibits STAT3 signaling
TumCP↓, EA inhibits cell proliferation, induces apoptosis
Apoptosis↑,
NF-kB↓, inhibiting nuclear factor-kappa B
EMT↓, suppressing epithelial–mesenchymal transition
RadioS↑, In liver cancer, EA exhibits radio-sensitizing effects
antiOx↑, As a potential antioxidant agent,
COX1↓, EA suppresses the expression of several factors, including COX1, COX2, c-myc, snail, and twist1
COX2↓,
cMyc↓,
Snail↓,
Twist↓,
MMP2↓, significantly decreased MMP-2 and MMP-9 expression and activity.
P90RSK↓,
CDK8↓, downregulate CDK8 expression and activity
PI3K↓, inactivating PI3K/Akt signaling
Akt↓,
TumCCA↑, promote cell cycle arrest
Casp8↑, ctivating caspase-8, and lowering proliferating cell nuclear antigen (PCNA) expression,
PCNA↓,
TGF-β↓,
Shh↓, suppression of the Akt, Shh, and Notch pathways, EA can prevent the growth, angiogenesis, and metastasis of pancreatic cancer
NOTCH↓,
IL6↓,
ALAT↓, decreasing liver injury biomarkers such as alanine transaminase (ALT), alkaline phosphatase (ALP), and aspartate aminotransferase (AST)
ALP↓,
AST↓,
VEGF↓,
P21↑,
*toxicity∅, no toxicity was found for a 50% effective dose by the intraperitoneal route inferior to 1 mg/kg/day
*Inflam↓, ncluding anti-inflammatory [10], anti-oxidant [11], anti-allergic [12], and anti-mutagenic [13] properties, as well as potential health advantages like gastroprotective [14], cardioprotective [15], neuroprotective [16, 17], and hepatoprotective [18,
*cardioP↑,
*neuroP↑,
*hepatoP↑,
ROS↑, Exposure to EAs induced apoptosis, accelerated cell cycle arrest, and elevated the generation of reactive oxygen intermediates [59].
*NRF2↓, As a potential antioxidant agent, it scavenges reactive oxygen species (ROS), and by upregulating of Nrf2,
*GSH↑, Moreover, EA increases reduced glutathione (GSH), which is critical for cellular defense against oxidative stress and liver damage,

1605-

EA,

Ellagic Acid and Cancer Hallmarks: Insights from Experimental Evidence

Review,

Var,

*BioAv↓, Within the gastrointestinal tract, EA has restricted bioavailability, primarily due to its hydrophobic nature and very low water solubility.
antiOx↓, strong antioxidant properties [12,13], anti-inflammatory effects
Inflam↓,
TumCP↓, numerous studies indicate that EA possesses properties that can inhibit cell proliferation
TumCCA↑, achieved this by causing cell cycle arrest at the G1 phase
cycD1/CCND1↓, reduction of cyclin D1 and E levels, as well as to the upregulation of p53 and p21 proteins
cycE/CCNE↓,
P53↑,
P21↑,
COX2↓, notable reduction in the protein expression of COX-2 and NF-κB as a result of this treatment
NF-kB↓,
Akt↑, suppressing Akt and Notch signaling pathways
NOTCH↓,
CDK2↓,
CDK6↓,
JAK↓, suppression of the JAK/STAT3 pathway
STAT3↓,
EGFR↓, decreased expression of epidermal growth factor receptor (EGFR)
p‑ERK↓, downregulated the expression of phosphorylated ERK1/2, AKT, and STAT3
p‑Akt↓,
p‑STAT3↓,
TGF-β↓, downregulation of the TGF-β/Smad3
SMAD3↓,
CDK6↓, EA demonstrated the capacity to bind to CDK6 and effectively inhibit its activity
Wnt/(β-catenin)↓, ability of EA to inhibit phosphorylation of EGFR
Myc↓, Myc, cyclin D1, and survivin, exhibited decreased levels
survivin↓,
CDK8↓, diminished CDK8 level
PKCδ↓, EA has demonstrated a notable downregulatory impact on the expression of classical isoenzymes of the PKC family (PKCα, PKCβ, and PKCγ).
tumCV↓, EA decreased cell viability
RadioS↑, further intensified when EA was combined with gamma irradiation.
eff↑, EA additionally potentiated the impact of quercetin in promoting the phosphorylation of p53 at Ser 15 and increasing p21 protein levels in the human leukemia cell line (MOLT-4)
MDM2↓, finding points to the ability of reduced MDM2 levels
XIAP↓, downregulation of X-linked inhibitor of apoptosis protein (XIAP).
p‑RB1↓, EA exerted a decrease in phosphorylation of pRB
PTEN↑, EA enhances the protein phosphatase activity of PTEN in melanoma cells (B16F10)
p‑FAK↓, reduced phosphorylation of focal adhesion kinase (FAK)
Bax:Bcl2↑, EA significantly increases the Bax/Bcl-2 rati
Bcl-xL↓, downregulates Bcl-xL and Mcl-1
Mcl-1↓,
PUMA↑, EA also increases the expression of Bcl-2 inhibitory proapoptotic proteins PUMA and Noxa in prostate cancer cells
NOXA↑,
MMP↓, addition to the reduction in MMP, the release of cytochrome c into the cytosol occurs in pancreatic cancer cells
Cyt‑c↑,
ROS↑, induction of ROS production
Ca+2↝, changes in intracellular calcium concentration, leading to increased levels of EndoG, Smac/DIABLO, AIF, cytochrome c, and APAF1 in the cytosol
Endoglin↑,
Diablo↑,
AIF↑,
iNOS↓, decreased expression of Bcl-2, NF-кB, and iNOS were observed after exposure to EA at concentrations of 15 and 30 µg/mL
Casp9↑, increase in caspase 9 activity in EA-treated pancreatic cancer cells PANC-1
Casp3↑, EA-induced caspase 3 activation and PARP cleavage in a dose-dependent manner (10–100 µmol/L)
cl‑PARP↑,
RadioS↑, EA sensitizes and reduces the resistance of breast cancer MCF-7 cells to apoptosis induced by γ-radiation
Hif1a↓, EA reduced the expression of HIF-1α
HO-1↓, EA significantly reduced the levels of two isoforms of this enzyme, HO-1, and HO-2, and increased the levels of sEH (Soluble epoxide hydrolase) in LnCap
HO-2↓,
SIRT1↓, EA-induced apoptosis was associated with reduced expression of HuR and Sirt1
selectivity↑, A significant advantage of EA as a potential chemopreventive, anti-tumor, or adjuvant therapeutic agent in cancer treatment is its relative selectivity
Dose∅, EA significantly reduced the viability of cancer cells at a concentration of 10 µmol/L, while in healthy cells, this effect was observed only at a concentration of 200 µmol/L
NHE1↓, EA had the capacity to regulate cytosolic pH by downregulating the expression of the Na+/H+ exchanger (NHE1)
Glycolysis↓, led to intracellular acidification with subsequent impairment of glycolysis
GlucoseCon↓, associated with a decrease in the cellular uptake of glucose
lactateProd↓, notable reduction in lactate levels in supernatant
PDK1?, inhibit pyruvate dehydrogenase kinase (PDK) -bind and inhibit PDK3
PDK1?,
ECAR↝, EA has been shown to influence extracellular acidosis
COX1↓, downregulation of cancer-related genes, including COX1, COX2, snail, twist1, and c-Myc.
Snail↓,
Twist↓,
cMyc↓,
Telomerase↓, EA, might dose-dependently inhibit telomerase activity
angioG↓, EA may inhibit angiogenesis
MMP2↓, EA demonstrated a notable reduction in the secretion of matrix metalloproteinase (MMP)-2 and MMP-9.
MMP9↓,
VEGF↓, At lower concentrations (10 and 20 μM), EA led to a substantial increase in VEGF levels. However, at higher doses (40 and 100 μM), a notable reduction in VEGF
Dose↝, At lower concentrations (10 and 20 μM), EA led to a substantial increase in VEGF levels. However, at higher doses (40 and 100 μM), a notable reduction in VEGF
PD-L1↓, EA downregulated the expression of the immune checkpoint PD-L1 in tumor cells
eff↑, EA might potentially enhance the efficacy of anti-PD-L1 treatment
SIRT6↑, EA exhibited statistically significant upregulation of sirtuin 6 at the protein level in Caco2 cells
DNAdam↓, increase in DNA damage

1621-

EA,

The multifaceted mechanisms of ellagic acid in the treatment of tumors: State-of-the-art

Review,

Var,

AntiCan↑, Studies have shown its anti-tumor effect in gastric cancer, liver cancer, pancreatic cancer, breast cancer, colorectal cancer, lung cancer and other malignant tumors
Apoptosis↑,
TumCP↓,
TumMeta↓,
TumCI↓,
TumAuto↑,
VEGFR2↓, inhibition of VEGFR-2 signaling
MAPK↓, MAPK and PI3K/Akt pathways
PI3K↓,
Akt↓,
PD-1↓, Downregulation of VEGFR-2 and PD-1 expression
NOTCH↓, Inhibition of Akt and Notch
PCNA↓, regulation of the expression of proliferation-related proteins PCNA, Ki67, CyclinD1, CDK-2, and CDK-6
Ki-67↓,
cycD1/CCND1↓,
CDK2↑,
CDK6↓,
Bcl-2↓,
cl‑PARP↑, up-regulated the expression of cleaved PARP, Bax, Active Caspase3, DR4, and DR5
BAX↑,
Casp3↑,
DR4↑,
DR5↑,
Snail↓, down-regulated the expression of Snail, MMP-2, and MMP-9
MMP2↓,
MMP9↓,
TGF-β↑, up-regulation of TGF-β1
PKCδ↓, Inhibition of PKC signaling
β-catenin/ZEB1↓, decreases the expression level of β-catenin
SIRT1↓, down-regulates the expression of anti-apoptotic protein, SIRT1, HuR, and HO-1 protein
HO-1↓,
ROS↑, up-regulates ROS
CHOP↑, activating the CHOP signaling pathway to induce apoptosis
Cyt‑c↑, releases cytochrome c
MMP↓, decreases mitochondrial membrane potential and oxygen consumption,
OCR↓,
AMPK↑, activates AMPK, and downregulates HIF-1α expression
Hif1a↓,
NF-kB↓, inhibition of NF-κB pathway
E-cadherin↑, Upregulates E-cadherin, downregulates vimentin and then blocks EMT progression
Vim↓,
EMT↓,
LC3II↑, Up-regulation of LC3 – II expression and down-regulation of CIP2A
CIP2A↓,
GLUT1↓, regulation of glycolysis-related gene GLUT1 and downstream protein PDH expression
PDH↝,
MAD↓, Downregulation of MAD, LDH, GR, GST, and GSH-Px related protein expressio
LDH↓,
GSTs↑,
NOTCH↓, inhibited the expression of Akt and Notch protein
survivin↓, survivin and XIAP was also significantly down-regulated
XIAP↓,
ER Stress↑, through ER stress
ChemoSideEff↓, could improve cisplatin-induced hepatotoxicity in colorectal cancer cells
ChemoSen↑, Enhancing chemosensitivity

27-

EA,

Ellagic acid inhibits human pancreatic cancer growth in Balb c nude mice

in-vivo,

PC,

PANC1

 PANC-1 cells were injected subcutaneously into Balb c nude mice, and tumor-bearing mice were treated with EA

HH↓,
Gli1↓, EA caused a significant inhibition in phospho-Akt, Gli1, Gli2, Notch1, Notch3, and Hey1.
GLI2↓,
CDK1/2/5/9↓,
p‑Akt↓,
NOTCH1↓,
Shh↓,
Snail↓,
E-cadherin↑,
NOTCH3↓,
HEY1↓,
TumCG↓, EA resulted in significant inhibition in tumor growth which was associated with suppression of cell proliferation and caspase-3 activation, and induction of PARP cleavage.
TumCP↓,
Casp3↑,
cl‑PARP↑,
Bcl-2↓, EA inhibited the expression of Bcl-2, cyclin D1, CDK2, and CDK6, and induced the expression of Bax in tumor tissues compared to untreated control group
cycD1/CCND1↓,
CDK2↓,
CDK6↓,
BAX↑,
COX2↓, EA inhibited the markers of angiogenesis (COX-2, HIF1α, VEGF, VEGFR, IL-6 and IL-8), and metastasis (MMP-2 and MMP-9) in tumor tissues.
Hif1a↓,
VEGF↓,
VEGFR2↓,
IL6↓,
IL8↓,
MMP2↓,
MMP9↓,
NA↓, EA could effectively inhibit human pancreatic cancer growth by suppressing Akt, Shh and Notch pathways

22-

EGCG,

Inhibition of sonic hedgehog pathway and pluripotency maintaining factors regulate human pancreatic cancer stem cell characteristics

in-vitro,

PC,

CD133+

in-vitro,

PC,

CD44+

in-vitro,

PC,

CD24+

in-vitro,

PC,

ESA+

 20-60 uM

HH↓, EGCG also inhibited the components of Shh pathway (smoothened, patched, Gli1 and Gli2)
Smo↓,
PTCH1↓,
PTCH2↓,
Gli1↓,
GLI2↓,
Gli↓,
Bcl-2↓, inhibiting the expression of Bcl-2 and XIAP, and activating caspase-3
XIAP↓,
Shh↓,
survivin↓,
Casp3↑,
Casp7↑,
CSCs↓, EGCG inhibited the expression of pluripotency maintaining transcription factors (Nanog, c-Myc and Oct-4), and self-renewal capacity of pancreatic CSCs.
Nanog↓,
cMyc↓,
OCT4↓,
EMT↓, EGCG inhibited EMT by inhibiting the expression of Snail, Slug and ZEB1, and TCF/LEF transcriptional activity,
Snail↓,
Slug↓,
Zeb1↓,
TumCMig↓, significantly reduced CSC’s migration and invasion, suggesting the blockade of signaling involved in early metastasis.
TumCI↓,
eff↑, combination of quercetin with EGCG had synergistic inhibitory effects on self-renewal capacity of CSCs through attenuation of TCF/LEF and Gli activities

685-

EGCG,

CUR,

SFN,

RES,

GEN

The “Big Five” Phytochemicals Targeting Cancer Stem Cells: Curcumin, EGCG, Sulforaphane, Resveratrol and Genistein

Analysis,

NA,

Bcl-2↓,
survivin↓,
XIAP↓,
EMT↓,
Apoptosis↑,
Nanog↓,
cMyc↓,
OCT4↓,
Snail↓,
Slug↓,
Zeb1↓,
TCF↓,

4682-

EGCG,

Human cancer stem cells are a target for cancer prevention using (−)-epigallocatechin gallate

Review,

Var,

CSCs↓, EGCG inhibits the transcription and translation of genes encoding stemness markers, indicating that EGCG generally inhibits the self-renewal of CSCs.
EMT↓, EGCG inhibits the expression of the epithelial-mesenchymal transition phenotypes of human CSCs.
ChemoSen↑, Green tea prevents human cancer, and the combination of EGCG and anticancer drugs confers cancer treatment with tissue-agnostic efficacy.
CD133↓, CD133, CD44, ALDH1A1, Nanog, Oct4
CD44↓,
ALDH1A1↓,
Nanog↓,
OCT4↓,
TumCP↓, These results show that EGCG inhibits proliferation and induces apoptosis of lung CSCs
Apoptosis↑,
p‑GSK‐3β↓, EGCG (0–100 μM) inhibited the phosphorylation of glycogen synthase kinase 3β (GSK3β) at Ser 9, which significantly increases the expression of GSK3β, and decreases the expression of β-catenin and its downstream target gene c-Myc.
GSK‐3β↑,
β-catenin/ZEB1↓,
cMyc↓,
XIAP↓, EGCG (30–60 μM) inhibits the expression of X-linked inhibitor of apoptosis protein (XIAP), Bcl2, and survivin as well as that of the EMT markers vimentin, Slug, Snail, and nuclear β-catenin.
Bcl-2↓,
survivin↓,
Vim↓,
Slug↓,
Snail↓,

4685-

EGCG,

Epigallocathechin gallate, polyphenol present in green tea, inhibits stem-like characteristics and epithelial-mesenchymal transition in nasopharyngeal cancer cell lines

in-vitro,

NPC,

TW01

in-vitro,

NPC,

TW06

CSCs↓, EGCG potently inhibited sphere formation and can eliminate the stem cell characteristics of NPC and inhibit the epithelial-mesenchymal transition (EMT) signatures.
EMT↓,
TumCMig↓, Inhibition on NPC sphere-derived cell colony formation, migration, and invasion by EGCG
TumCI↓,
OCT4↓, EGCG inhibited the expression of Klf-4 and Oct-4 in sphere-derived cells.
Snail↓, EGCG significantly inhibited the levels of Snail, Vimentin and increased E-Cadherin expression in a dose-dependent manner
Vim↓,
E-cadherin↓,
HSP70/HSPA5↓, EGCG suppresses the expression of HSP70 and HSP90, and exhibits anti-tumor activity in vitro and in vivo
HSP90↓,
AntiTum↓,

1155-

The anti-cancer effects of fucoidan: a review of both in vivo and in vitro investigations

Review,

NA,

100 μg/mL

*toxicity↓, Sprague–Dawley rats, researchers didn’t observe significant side effects when taking 0–1000 mg/kg fucoidan orally for 28 days.
Casp3↑,
Casp7↑,
Casp8↑,
Casp9↑,
VEGF↓,
angioG↓,
PI3K↓,
Akt↓,
PARP↑,
Bak↑,
BID↑,
Fas↑,
Mcl-1↓,
survivin↓,
XIAP↓,
ERK↓,
EMT↓, Fucoidan can reverse the EMT effectively
EM↑,
IM↓,
Snail↓,
Slug↓,
Twist↓,

2857-

FIS,

A review on the chemotherapeutic potential of fisetin: In vitro evidences

Review,

Var,

COX2↓, fisetin altered the expression of cyclooxygenase 2 (COX2) thereby suppressed the secretion of prostaglandin E2 ultimately resulting in the inhibition of epidermal growth factor receptor (EGFR) and NF-ÎºB in human colon cancer cells HT29
PGE2↓,
EGFR↓,
Wnt↓, fisetin treatment inhibited the stimulation of Wnt signaling pathway via downregulating the expression of Î²-catenin and Tcell factor (TCF) 4
β-catenin/ZEB1↓,
TCF↑,
Apoptosis↑, fisetin triggers apoptosis in U266 cells through multiple pathways: enhancing the activation of caspase-3 and PARP cleavage, decreasing the expression of anti-apoptotic proteins (Bcl-2 and Mcl-1 L ),
Casp3↑,
cl‑PARP↑,
Bcl-2↓,
Mcl-1↓,
BAX↑, ncreasing the expression of pro-apoptotic proteins (Bax, Bim, and Bad)
BIM↑,
BAD↑,
Akt↓, decreasing the phosphorylation of AKT and mTOR and elevating the expression of acetyl CoA carboxylase (ACC
mTOR↓,
ACC↑,
Cyt‑c↑, release the cytochrome c and Smac/Diablo into the cytosol
Diablo↑,
cl‑Casp8↑, fisetin exhibited an increased level of cleaved caspase-8, Fas/Fas ligand, death receptor 5/TRAIL, and p53 levels in HCT-116 cells
Fas↑,
DR5↑,
TRAIL↑,
Securin↓, Securin gets degraded on exposure to fisetin in colon cancer cells.
CDC2↓, fisetin decreased the expression of cell division cycle proteins (CDC2 and CDC25C)
CDC25↓,
HSP70/HSPA5↓, Fisetin induced apoptosis as a result of the downregulation of HSP70 and BAG3 and the inhibition of Bcl-2, Bcl-x L and Mcl-1. T
CDK2↓, AGS 0, 25, 50, 75 μM – 24 and 48 h ↓CDK2, ↓CDK4, ↓cyclin D1, ↑casapse-3 cleavage
CDK4↓,
cycD1/CCND1↓,
MMP2↓, A549 0, 1, 5, 10 μM- 24 and 48 hr: ↓MMP-2, ↓u-PA, ↓NF- κB, ↓c-Fos, ↓c-Jun
uPA↓,
NF-kB↓,
cFos↓,
cJun↓,
MEK↓, ↓ MEK1/2 and ERK1/2 phosphorylation, ↓N-cadherin, ↓vimentin, ↓snail, ↓fibronectin, ↑E-cadherin, ↑desmoglein
p‑ERK↓,
N-cadherin↓,
Vim↓,
Snail↓,
Fibronectin↓,
E-cadherin↓,
NF-kB↑, increased expression of NF-κB p65 leading to apoptosis was due to ROS generation on exposure to fisetin
ROS↑,
DNAdam↑, increased ROS triggered cell death through PARP cleavage, DNA damage and mitochondrial membrane depolarization.
MMP↓,
CHOP↑, Though fisetin upregulated CHOP expression and increased the production of ROS, these events fail to induce apoptosis in Caki cells.
eff↑, 50 μM fisetin + 1 mM melatonin Sk-mel-28 Enhances anti-tumour activity [54] 20 μM fisetin + 1 mM melatonin MeWo Enhances anti-tumour activity [54] 10 μM fisetin + 0.1 μM melatonin A549 Induces autophagic cell death
ChemoSen↑, 20 μM fisetin + 5 μM sorafenib A375, SK-MEL-28 Suppresses invasion and metastasis [44] 40 μM fisetin + 10 μM cisplatin A549, A549-CR Enhances apoptosis

2845-

FIS,

Fisetin: A bioactive phytochemical with potential for cancer prevention and pharmacotherapy

Review,

Var,

PI3K↓, block multiple signaling pathways such as the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) and p38
Akt↓,
mTOR↓,
p38↓,
*antiOx↑, antioxidant, anti-inflammatory, antiangiogenic, hypolipidemic, neuroprotective, and antitumor effect
*neuroP↑,
Casp3↑, U266 cancer cell line through activation of caspase-3, downregulation of Bcl-2 and Mcl-1L, upregulation of Bax, Bim and Bad
Bcl-2↓,
Mcl-1↓,
BAX↑,
BIM↑,
BAD↑,
AMPK↑, activation of 5'adenosine monophosphate-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC) and decreased phosphorylation of AKT and mTOR were also observed
ACC↑,
DNAdam↑, DNA fragmentation, mitochondrial membrane depolarizatio
MMP↓,
eff↑, fisetin in combination with a citrus flavanone, hesperetin mediated apoptosis by mitochondrial membrane depolarization and caspase-3 act
ROS↑, NCI-H460 human non-small cell lung cancer line, fisetin generated reactive oxygen species (ROS), endoplasmic reticulum (ER) stress
cl‑PARP↑, fisetin treatment resulted in PARP cleavage
Cyt‑c↑, release of cyt. c
Diablo↑, release of cyt. c and Smac/DIABLO from mitochondria,
P53↑, increased p53 protein levels
p65↓, reduced phospho-p65 and Myc oncogene expression
Myc↓,
HSP70/HSPA5↓, fisetin causes inhibition of proliferation by the modulation of heat shock protein 70 (HSP70), HSP27
HSP27↓,
COX2↓, anti-proliferative effects of fisetin through the activation of apoptosis via inhibition of cyclooxygenase-2 (COX-2) and Wnt/EGFR/NF-κB signaling pathways
Wnt↓,
EGFR↓,
NF-kB↓,
TumCCA↑, The anti-proliferative effects of fisetin and hesperetin were shown to be occurred through S, G2/M, and G0/G1 phase arrest in K562 cell progression
CDK2↓, decrease in levels of cyclin D1, cyclin A, Cdk-4 and Cdk-2
CDK4↓,
cycD1/CCND1↓,
cycA1/CCNA1↓,
P21↑, increase in p21 CIP1/WAF1 levels in HT-29 human colon cancer cell
MMP2↓, fisetin has exhibited tumor inhibitory effects by blocking matrix metalloproteinase-2 (MMP- 2) and MMP-9 at mRNA and protein levels,
MMP9↓,
TumMeta↓, Antimetastasis
MMP1↓, fisetin also inhibited the MMP-14, MMP-1, MMP-3, MMP-7, and MMP-9
MMP3↓,
MMP7↓,
MET↓, promotion of mesenchymal to epithelial transition associated with a decrease in mesenchymal markers i.e. N-cadherin, vimentin, snail and fibronectin and an increase in epithelial markers i.e. E-cadherin
N-cadherin↓,
Vim↓,
Snail↓,
Fibronectin↓,
E-cadherin↑,
uPA↓, fisetin suppressed the expression and activity of urokinase plasminogen activator (uPA)
ChemoSen↑, combination treatment of fisetin and sorafenib reduced the migration and invasion of BRAF-mutated melanoma cells both in in-vitro
EMT↓, inhibited epithelial to mesenchymal transition (EMT) as observed by a decrease in N-cadherin, vimentin and fibronectin and an increase in E-cadherin
Twist↓, inhibited expression of Snail1, Twist1, Slug, ZEB1 and MMP-2 and MMP-9
Zeb1↓,
cFos↓, significant decrease in NF-κB, c-Fos, and c-Jun levels
cJun↓,
EGF↓, Fisetin inhibited epidermal growth factor (EGF)
angioG↓, Antiangiogenesis
VEGF↓, decreased expression of endothelial nitric oxide synthase (eNOS) and VEGF, EGFR, COX-2
eNOS↓,
*NRF2↑, significantly increased nuclear translocation of Nrf2 and antioxidant response element (ARE) luciferase activity, leading to upregulation of HO-1 expression
HO-1↑,
NRF2↓, Fisetin also triggered the suppression of Nrf2
GSTs↓, declined placental type glutathione S-transferase (GST-p) level in the liver of the fisetin- treated rats with hepatocellular carcinoma (HCC)
ATF4↓, Fisetin also rapidly increased the levels of both Nrf2 and ATF4

1116-

GI,

6-Shogaol Inhibits the Cell Migration of Colon Cancer by Suppressing the EMT Process Through the IKKβ/NF-κB/Snail Pathway

in-vitro,

Colon,

Caco-2

20, 40, 60, 80, and 100 µM

86.63 µM

in-vitro,

CRC,

HCT116

45.25 µM

TumCG↓,
Apoptosis↑,
TumCMig↓,
MMP2↓, 80 µM
N-cadherin↓,
IKKα↓, IKKβ
p‑NF-kB↓,
Snail↓,
VEGF↓,

1643-

HCAs,

Mechanisms involved in the anticancer effects of sinapic acid

Review,

Var,

*BioAv↓, Studies have shown that SA is poorly soluble in water, but soluble in carbitol and freely soluble in DMSO
*toxicity↓, SA is found to be generally non-toxic
Dose∅, oral administration of SA up to 80 mg/kg body weight reduced the number of aberrant crypt foci up to 34.55%
ROS⇅, Other than its potent antioxidant function, SA also possesses pro-oxidant effect that has been identified to affect the redox state of tumor cells
ROS↑, SA at higher concentrations acts as a potent pro-oxidant agent, resulting in increased generation of free radicals. (50 and 75 μM) increased ROS accumulation
Igs↑, SA administration markedly improved the levels of IgG and IgA in
TumCCA↑, SA induced G2/M phase cell cycle arrest
TumAuto↑, autophagy inducing effect of SA has been reported by Zhao et al. (2021) in HepG2 and SMMC-7721 cells
eff↑, Beclin, Atg 5 increased and expression of p62 decreased in SA along with cisplatin treated HepG2 and SMMC-7721 cells
angioG↓, SA has been demonstrated to inhibit angiogenesis, cell invasion and metastasis in cancer cells
TumCI↓,
TumMeta↓,
EMT↓, SA (10 mM) treated cells showed decreased protein expression of EMT related proteins such as vimentin, MMP-9, MMP-2, and Snail and increased expression of E-cadherin in PANC-1 and SW1990 cell lines.
Vim↓,
MMP9↓,
MMP2↓,
Snail↓,
E-cadherin↑,
p‑Akt↓, SA treatment downregulated phosphorylated AKT and Gsk-3β in PANC-1 and SW1990 prostate cancer cell lines.
GSK‐3β↓,
TumCP↓, SA can inhibit cell proliferation in prostate cancer
ChemoSen↑, SA acts in collaboration with other chemotherapeutic agents to improve treatment sensitivity

4659-

HNK,

Honokiol Eliminates Human Oral Cancer Stem-Like Cells Accompanied with Suppression of Wnt/β-Catenin Signaling and Apoptosis Induction

in-vitro,

Oral,

cl‑Casp3↑, Apoptosis of honokiol-treated SP cells was evidenced by increased annexin V staining and cleaved caspase-3 as well as decreased Survivin and Bcl-2.
survivin↓,
Bcl-2↓,
CD44↓, Mechanistically, honokiol inhibited the CD44 and Wnt/β-catenin signaling of SP cells
Wnt↓,
β-catenin/ZEB1↑,
EMT↓, EMT markers such as Slug and Snail were markedly suppressed by honokiol.
Slug↓,
Snail↓,
CSCs↓, Our findings indicate honokiol may be able to eliminate oral cancer stem cells through apoptosis induction, suppression of Wnt/β-catenin signaling, and inhibition of EMT.
Apoptosis↑, Honokiol-Induced Apoptosis of SAS SP Cells

2880-

HNK,

Honokiol inhibits breast cancer cell metastasis by blocking EMT through modulation of Snail/Slug protein translation

in-vitro,

BC,

MCF-7

in-vitro,

BC,

MDA-MB-231

in-vitro,

BC,

4T1

in-vivo,

NA,

50 mg/kg every day, intraperitoneal (i.p.), 6 times per week for 30 days

mouse

tumCV↓, HNK (10−70 μmol/L) dose-dependently inhibited the viability of human mammary epithelial tumor cell lines MCF7, MDA-MB-231, and mouse mammary tumor cell line 4T1
E-cadherin↑, dose-dependently upregulated the epithelial marker E-cadherin and downregulated the mesenchymal markers such as Snail, Slug, and vimentin at the protein level in breast cancer cells
Snail↓,
Slug↓,
Vim↓,
TumMeta↓, HNK inhibits the in vivo metastasis of breast cancer cells
p‑eIF2α↑, increased eIF2α phosphorylation revealed that HNK might reduce protein translation.

2882-

HNK,

Honokiol Suppresses Perineural Invasion of Pancreatic Cancer by Inhibiting SMAD2/3 Signaling

in-vitro,

PC,

PANC1

TumCI↓, HNK can inhibit the invasion and migration of pancreatic cancer cells.
TumCMig↓,
p‑SMAD2↓, partially mediated by inhibition of SMAD2/3 phosphorylation.
p‑SMAD3↓,
EMT↓, HNK Inhibits Pancreatic Cancer Malignant Behaviors and EMT
N-cadherin↓, expression of N-cadherin and Vimentin was gradually downregulated, while HNK promoted the expression of E-cadherin in PANC-1
Vim↓,
E-cadherin↑,
Snail↓, HNK can inhibit breast cancer cell metastasis by blocking EMT through downregulating Snail/Slug protein translation
Slug↓,
Rho↓, Honokiol inhibits the migration of renal cell carcinoma through activation of the RhoA/ROCK/MLC signaling pathway
ROCK1↓,

2883-

HNK,

Honokiol targets mitochondria to halt cancer progression and metastasis

Review,

Var,

ChemoSen↑, Combination of HNK with many traditional chemotherapeutic drugs as well as radiation sensitizes cancer cells to apoptotic death
BBB↓, HNK is also capable of crossing the BBB
Ca+2↑, HNK promotes human glioblastoma cancer cell apoptosis via regulation of Ca(2+) channels
Cyt‑c↑, release of mitochondrial cytochrome c and activation of caspase-3
Casp3↑,
chemoPv↑, potent chemopreventive agent against lung SCC development in a carcinogen-induced lung SCC murine model
OCR↓, HNK treatment results in a decreased oxygen consumption rate (OCR) in whole intact cells, rapidly, and persistently inhibiting mitochondrial respiration, which leads to the induction of apoptosis
mitResp↓,
Apoptosis↑,
RadioS↑, Honokiol as a chemo- and radiosensitizer
NF-kB↓, HNK as an anticancer drug is its potential to inhibit multiple important survival pathways, such as NF-B and Akt
Akt↓,
TNF-α↓, by inhibiting TNF-induced nerve growth factor IB expression in breast cancer cells
PGE2↓, reduced prostaglandin E2 (PGE2) and vascular endothelial growth factor (VEGF) secretion levels
VEGF↓,
NO↝, HNK inhibits cancer cell migration by targeting nitric oxide and cyclooxygenase-2 or Ras GTPase-activating-like protein (IQGAP1) [
COX2↓,
RAS↓,
EMT↓, HNK can reverse the epithelial-mesenchymal-transition (EMT) process, which is a key step during embryogenesis, cancer invasion, and metastasis,
Snail↓, HNK reduced the expression levels of Snail, N-cadherin and -catenin, which are mesenchymal markers, but increased E-cadherin,
N-cadherin↓,
β-catenin/ZEB1↓,
E-cadherin↑,
ER Stress↑, induction of ER stress
p‑STAT3↓, HNK inhibited STAT3 phosphorylation
EGFR↓, inhibiting EGFR phosphorylation and its downstream signaling pathways such as the mTOR signaling pathway
mTOR↓,
mt-ROS↑, We demonstrated that HNK treatment suppresses mitochondrial respiration and increases generation of ROS in the mitochondria, leading to the induction of apoptosis in lung cancer cells
PI3K↓, inhibition of PI3K/Akt/ mTOR, EMT, and Wnt signaling pathways.
Wnt↓,

2884-

HNK,

Honokiol inhibits EMT-mediated motility and migration of human non-small cell lung cancer cells in vitro by targeting c-FLIP

in-vitro,

Lung,

A549

in-vitro,

Lung,

H460

EMT↓, HNK inhibits EMT-mediated motility and migration of human NSCLC cells in vitro by targeting c-FLIP,
cFLIP↓,
N-cadherin↓, increased c-FLIP, N-cadherin (a mesenchymal marker), snail (a transcriptional modulator) and p-Smad2/3 expression, and decreased IκB levels in the cells; these changes were abrogated by co-treatment with HNK (30 μmol/L)
Snail↓,
p‑SMAD2↓,
p‑SMAD3↓,
IKKα↑,
TumCMig↓, HNK inhibits the migration of A549 and H460 cells induced by TNF-α+TGF-β1

2891-

HNK,

Honokiol, an Active Compound of Magnolia Plant, Inhibits Growth, and Progression of Cancers of Different Organs

Review,

Var,

AntiCan↑, honokiol possesses anti-carcinogenic, anti-inflammatory, anti-oxidative, anti-angiogenic as well as inhibitory effect on malignant transformation of papillomas to carcinomas in vitro and in vivo animal models without any appreciable toxicity.
Inflam↓,
antiOx↑,
selectivity↑,
*toxicity↓,
cycD1/CCND1↓, honokiol resulted in inhibition of UVB-induced expression levels of cyclins (cyclins D1, D2, and E) and CDKs in skin tumors
cycE/CCNE↓,
CDK2↓,
CDK4↓,
TumMeta↓, Honokiol Inhibits Metastatic Potential of Melanoma Cells
NADPH↓, Honokiol not only reduces the NADPH oxidase activity
MMP2↓, honokiol treatment reduces the expression of MMP-2 and MMP-9
MMP9↓,
p‑mTOR↓, honokiol caused significant downregulation of mTOR phosphorylation
EGFR↓, honokiol decreases the expression levels of total EGFR
EMT↓, honokiol effectively inhibits EMT in breast cancer cells
SIRT1↑, onokiol increases the expressions of SIRT1 and SIRT3,
SIRT3↑,
EZH2↓, depletion of EZH2 by honokiol treatment inhibited cell proliferation
Snail↓, significantly down regulates Snail, vimentin, N-cadherin expression, and upregulates cytokeratin-18 and E-cadherin expression
Vim↓,
N-cadherin↓,
E-cadherin↑,
COX2↓, honokiol as an inhibitor of COX-2 expression
NF-kB↓, inhibited transcriptional activity of NF-jB,
*ROS↓, Inhibition of UVR-induced inflammatory mediators as well as ROS by honokiol treatment contributes to the prevention of UVR-induced skin tumor development
Ca+2↑, excessive influx of cytosolic calcium ion into the mitochondria triggers dysfunction of the mitochon- drial membrane permeabilization with mitochondrial ROS induction
ROS↑,

4636-

HT,

Hydroxytyrosol inhibits cancer stem cells and the metastatic capacity of triple-negative breast cancer cell lines by the simultaneous targeting of epithelial-to-mesenchymal transition, Wnt/ß-catenin and TGFß signaling

in-vitro,

BC,

SUM159

in-vitro,

BC,

MDA-MB-231

in-vitro,

BC,

HS587T

in-vitro,

BC,

BT549

Wnt↓, HT suppressed Wnt/ß-catenin signaling by decreasing p-LRP6, LRP6, ß-catenin and cyclin D1 protein expression and the EMT markers SLUG, ZEB1, SNAIL and VIMENTIN.
β-catenin/ZEB1↓,
LRP6↓,
cycD1/CCND1↓,
EMT↓,
Slug↓,
Zeb1↓,
Snail↓,
Vim↓,
TGF-β↓, correlated with a less TGFß activity.
CSCs↓, we report for the first time the inhibitory role of HT on BCSCs and tumor cell migration by targeting EMT, Wnt/ß-catenin and TGFß signaling pathways.
TumCMig↓,
chemoP↑, chemopreventive compound HT as a novel candidate to be investigated as an alternative targeted therapy for TNBC.

4640-

HT,

The anti-cancer potential of hydroxytyrosol

Review,

Var,

selectivity↑, Hydroxytyrosol selectively kills cancer cells with minimal impact on normal cells by activating both intrinsic and extrinsic apoptotic pathways.
MMP↓, Disruption of Mitochondrial Membrane Potential
Cyt‑c↑, HT reduces mitochondrial membrane potential (ΔΨm), leading to the release of cytochrome c into the cytoplasm, activating caspase-9 and caspase-3, and triggering an apoptotic cascade (Cancer Letters, 2021).
Casp9↑,
Casp3↑,
Bcl-2↓, It downregulates anti-apoptotic proteins (Bcl-2, Bcl-xL) and upregulates pro-apoptotic proteins (Bax, Bak), promoting mitochondrial outer membrane permeabilization (MPTP opening) (Molecular Oncology, 2022).
BAX↑,
MPT↑,
Fas↑, Activation of Death Receptor-Mediated Extrinsic Apoptotic Pathway: Fas/FasL Pathway
PI3K↓, Suppression of PI3K/Akt/mTOR Pathway
Akt↓,
mTOR↓,
Mcl-1↓, decreases the expression of anti-apoptotic proteins (Mcl-1, Survivin) (Cancer Research, 2021).
survivin↓,
STAT3↓, Blockade of STAT3 Pathway
EMT↓, Hydroxytyrosol blocks key steps of tumor metastasis by regulating epithelial-mesenchymal transition (EMT), cell adhesion, invasion, and angiogenesis.
TumCI↓,
angioG↓,
E-cadherin↑, Upregulation of E-cadherin and Downregulation of N-cadherin
N-cadherin↓,
Snail↓, Inhibition of Snail/Twist Transcription Factors
Twist↓,
MMPs↓, Inhibition of Matrix Metalloproteinases (MMPs)
MMP2↓, HT downregulates the activity of MMP-2 and MMP-9, reducing extracellular matrix (ECM) degradation and inhibiting tumor cell invasion (Cancer Prevention Research, 2021).
MMP9↓,
VEGF↓, Suppression of VEGF/VEGFR Pathway
VEGFR2↓,
Hif1a↓, Degradation of HIF-1α: It inhibits the stabilization of HIF-1α under hypoxic conditions, reducing transcription of downstream pro-angiogenic genes (Molecular Cancer Therapeutics, 2021).
CSCs↓, Inhibition of Tumor Stem Cell Properties
CD44↓, Downregulation of CD44/ALDH1 Markers
Wnt↓, Inhibition of Wnt/β-catenin Pathway
β-catenin/ZEB1↓,

4632-

HT,

in-vitro,

BC,

MDA-MB-231

in-vitro,

BC,

BT549

in-vitro,

BC,

SUM159

CSCs↓, HT reduced BCSCs self-renewal, ALDH+ (aldehyde dehydrogenase) and CD44+/CD24-/low subpopulations, tumor cell migration and invasion.
TumCMig↓,
TumCI↓,
β-catenin/ZEB1↓, HT suppressed Wnt/β-catenin signaling by decreasing p-LRP6, LRP6, β-catenin and cyclin D1 protein expression and the EMT markers SLUG, ZEB1, SNAIL and VIMENTIN.
Wnt↓,
p‑LRP6↓,
LRP6↓,
cycD1/CCND1↓,
EMT↓,
Slug↓,
Zeb1↓,
Snail↓,
Vim↓,
SMAD2↓, Finally, HT inhibited p-SMAD2/3 and SMAD2/3 in SUM159PT, BT549 and MDA-MB-231 cells, what was correlated with a less TGFβ activity.
SMAD3↓,
TGF-β↓,

1121-

JG,

Juglone suppresses epithelial-mesenchymal transition in prostate cancer cells via the protein kinase B/glycogen synthase kinase-3β/Snail signaling pathway

in-vitro,

Pca,

LNCaP

E-cadherin↑,
N-cadherin↓,
Vim↓,
Snail↓,
GSK‐3β↑, prevented inactivation

Showing Research Papers: 1 to 50 of 90
Page 1 of 2 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 90

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 2, GSH↑, 1, NRF2↓, 1, NRF2↑, 1, Prx↑, 1, ROS↓, 2, SOD2↑, 1,

Cell Death ⓘ

Casp3?, 1, iNOS↓, 1,

Migration ⓘ

Ca+2↝, 1, cal2↓, 1, E-cadherin↑, 1, F-actin↓, 1, N-cadherin↓, 1, Snail↓, 1, TumCMig↓, 1, Vim↓, 1, ZO-1↑, 1,

Immune & Inflammatory Signaling ⓘ

COX2↓, 1, Inflam↓, 1, NF-kB↓, 1,

Drug Metabolism & Resistance ⓘ

BioAv↓, 3,

Clinical Biomarkers ⓘ

AST↓, 1,

Functional Outcomes ⓘ

cardioP↑, 1, hepatoP↑, 1, neuroP↑, 2, toxicity↓, 4, toxicity∅, 1,
Total Targets: 28

Scientific Paper Hit Count for: Snail, Snail

7 Sulforaphane (mainly Broccoli)
7 Quercetin
6 Resveratrol
6 EGCG (Epigallocatechin Gallate)
6 Honokiol
5 Apigenin (mainly Parsley)
4 Ellagic acid
3 Curcumin
3 HydroxyTyrosol
3 Luteolin
3 Urolithin
2 Alpha-Lipoic-Acid
2 Ashwagandha(Withaferin A)
2 Baicalein
2 Berberine
2 Chrysin
2 Fisetin
2 Piperine
2 Pterostilbene
1 Astragalus
1 Cisplatin
1 Baicalin
1 Betulinic acid
1 Butyrate
1 Caffeic acid
1 Capsaicin
1 Cannabidiol
1 Chlorogenic acid
1 Citric Acid
1 Cyclopamine
1 Genistein (soy isoflavone)
1 Fucoidan
1 Ginger/6-Shogaol/Gingerol
1 Hydroxycinnamic-acid
1 Juglone
1 Magnolol
1 5-fluorouracil
1 Metformin
1 Naringin
1 Phenethyl isothiocyanate
1 Piperlongumine
1 isoflavones
1 Rosmarinic acid
1 salinomycin
1 Sanguinarine
1 Silymarin (Milk Thistle) silibinin
1 Shikonin
1 Taurine
1 Thymoquinone
1 Vitamin D3

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

Snail Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

NA, unassigned ⓘ

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Cellular Microenvironment ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Cell Death ⓘ

Migration ⓘ

Immune & Inflammatory Signaling ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

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