SMAD4 Cancer Research Results

SMAD4, SMAD family member 4: Click to Expand ⟱
Source: CGL-Driver Genes
Type: TSG
SMAD4 is a critical tumor suppressor gene that plays a significant role in the TGF-β signaling pathway, which regulates various cellular processes, including cell growth, differentiation, and apoptosis.
Plays a critical role in the TGF-beta signaling pathway.
Scientific Papers found: Click to Expand⟱
1093- And,    Andrographolide attenuates epithelial‐mesenchymal transition induced by TGF‐β1 in alveolar epithelial cells
- in-vitro, Lung, A549
TGF-β↓,
TumCMig↓,
MMP2↓,
MMP9↓,
ECM/TCF↓,
p‑SMAD2↓,
p‑SMAD3↓,
SMAD4↓,
p‑ERK↓,
ROS↓, reduced (TGF‐β1‐induced) intracellular ROS generation
NOX4↓,
SOD2↑,
SIRT1↑, Andro protects AECs from EMT partially by activating Sirt1/FOXO3‐mediated anti‐oxidative stress pathway
FOXO3↑,

5502- Ba,    An overview of pharmacological activities of baicalin and its aglycone baicalein: New insights into molecular mechanisms and signaling pathways
- Review, Var, NA
*AntiCan↑, antibacterial, antiviral, anticancer, anticonvulsant, anti-oxidant, hepatoprotective, and neuroprotective effects.
*antiOx↑,
*hepatoP↑,
*neuroP↑,
*ROS↓, pharmacological properties of baicalin and baicalein are due to their abilities to scavenge reactive oxygen species (ROS)
Ca+2↑, Baicalein mainly induced apoptosis through Ca+2 influx via Ca2+ release from the reticulum to cytosol dependent on phospholipase C protein
ROS↑, ROS production is associated with baicalein-induced apoptosis via Ca2+-dependent apoptosis in tongue and breast cancer cells (78, 79)
BAX↑, The level of Bax/Bcl-2 increased and caspase-3 and -9 were activated following the release of cytochrome C (80).
Casp3↑,
Casp9↑,
Cyt‑c↑,
MMP↓, In gastric cancer cells, baicalein mediated apoptosis in a dose-dependent manner through disruption of mitochondrial membrane potential
Mcl-1↓, In pancreatic cancer cells, baicalein induced apoptosis via suppression of the Mcl-1 protein.
PI3K↓, In HepG2 cells, baicalin-copper induced apoptosis through down-regulation of phosphoinositide-3 kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway
Akt↓,
mTOR↓,
BAD↓, Studies demonstrated that baicalein treatment suppressed Bad, ERK1/2 phosphorylation, and MEK1 expression both in vitro and in vivo.
ERK↓,
MEK↓,
DR5↑, Baicalein enhanced the activity of death receptor-5 (DR5) in prostate cancer PC3 cells.
Fas↑, baicalin is the active ingredient that acts as Fas ligand and caused up-regulation of Fas protein (89).
TumMeta↓, Baicalin/baicalein not only induced apoptosis in cancer cells but also suppressed metastasis.
EMT↓, both baicalin and baicalein inhibited epithelial-mesenchymal transition (EMT) through the suppression of TGF-β in breast epithelial cells through the NF-κB pathway (92).
SMAD4↓, baicalein suppressed metastasis in gastric cancer through inactivation of the Smad4/TGF-β pathway (93).
TGF-β↓,
MMP9↓, baicalin and baicalein inhibition of the expression level of matrix metalloproteinases (MMP) such as MMP-9 and MMP-2 in liver, breast, lung, ovarian, gastric, and colorectal cancers and glioma
MMP2↓,
HIF-1↓, Baicalin attenuated lung metastasis through inhibition of hypoxia-inducible factor (HIF)
12LOX↓, Baicalein acts as an anticancer agent via inhibiting 12-lipooxygenase (12-LOX),

5501- Ba,    Therapeutic effects and mechanisms of action of Baicalein on stomach cancer: a comprehensive systematic literature review
- Review, GC, NA
AntiCan↑, The review demonstrated that BC exerts therapeutic effects on GC through multiple biochemical mechanisms.
Apoptosis↑, BC plays an important role in inducing apoptosis, inhibiting cell proliferation, and suppressing metastasis in GC cells.
TumCP↓,
TumMeta↓,
BAX↑, graphical abstract
TumAuto↑,
ROS↑,
NRF2↝, BC induced apoptosis and autophagy in MGC-803, SGC-7901, and HGC-27 cells, enhancing cisplatin sensitivity via suppression of the AKT/mTOR pathway and modulation of the Nrf2/Keap1 axis.
PI3K↓,
Akt↓,
NF-kB↓,
TGF-β↓,
SMAD4↓,
GPx4↓, It induces autophagy and ferroptosis, partly through p53 activation and suppression of SLC7A11/GPX4, and disrupts mitochondrial membrane potential via reactive oxygen species (ROS) generation [31, 37]
MMP↓,
*HO-1↑, BC stabilizes Nrf2, leading to the induction of antioxidant enzymes such as HO-1, GST, and NQO1, which mitigate oxidative stress and contribute to its antitumor effects [38].
*GSTs↑,
*antiOx↑,
*AntiTum↑,
*NRF2↑,
ChemoSen↑, BC induced apoptosis and autophagy in MGC-803, SGC-7901, and HGC-27 cells, enhancing cisplatin sensitivity via suppression of the AKT/mTOR pathway and modulation of the Nrf2/Keap1 axis.
Akt↓,
mTOR↓,
FAK↓, reducing FAK expression
Ki-67↓, Immunohistochemical analysis also revealed lower Ki-67 levels, indicating reduced cellular proliferation.

1110- EA,  GEM,    Ellagic Acid Resensitizes Gemcitabine-Resistant Bladder Cancer Cells by Inhibiting Epithelial-Mesenchymal Transition and Gemcitabine Transporters
- vitro+vivo, Bladder, NA
TGF-β↓,
SMAD2↓,
SMAD3↓,
SMAD4↓,

1072- EGCG,    Epigallocatechin gallate (EGCG) suppresses epithelial-Mesenchymal transition (EMT) and invasion in anaplastic thyroid carcinoma cells through blocking of TGF-β1/Smad signaling pathways
- in-vitro, Thyroid, 8505C
EMT↓,
TumCI↓,
TumCMig↓,
TGF-β↓,
p‑SMAD2↓,
p‑SMAD3↓,
SMAD4↓,

1323- EMD,    Anticancer action of naturally occurring emodin for the controlling of cervical cancer
- Review, Cerv, NA
TumCCA↑, cell cycle arrest in the G2/M phase
DNAdam↑,
mTOR↓,
Casp3↑,
Casp8↑,
Casp9↑,
TGF-β↑,
SMAD3↓,
p‑SMAD4↓,
ROS↑,
MMP↓,
CXCR4↓,
HER2/EBBR2↓,
ER Stress↓,
TumAuto↑, can increase the level of autophagy in A549 lung cancer cells, but did not affect autophagy in healthy non-cancerous Ha CaT cells
NOTCH1↓,

7378- RS,    Reserpine inhibits DNA repair, cell proliferation, invasion and induces apoptosis in oral carcinogenesis via modulation of TGF-β signaling
*antiOx↑, Reserpine is a natural indole alkaloid isolated from Rauwolfia serpentina and has potent antioxidant, antimicrobial, and anti-mutagenic properties.
*AntiBio↑,
TGF-β↓, reserpine inhibits TGF-β dependent Smad2/3/4 phosphorylation, thereby blockage Smad3/Snail activation and Smad2/4 nuclear translocation.
p‑SMAD3↓,
p‑SMAD2↓,
p‑SMAD4↓,
SMAD3↓,
Snail↓,
ERCC1↓, downregulating ERCC1, XPF, Ku70, DNA-PKcs, PCNA, cyclin D1, HIF-1α, IL-6, Mcl-1
ERCC4/XPF↓,
Ku70/XRCC6↓,
PCNA↓,
cycD1/CCND1↓,
Hif1a↓,
IL6↓,
Mcl-1↓,
BAX↑, stimulates Bax, cytochrome C, Apaf-1, caspase-9, caspase-3 and PARP protein expressions.
Cyt‑c↑,
APAF1↑,
Casp9↑,
Casp3↑,
PARP↑,
DNArepair↓, therapeutic potential of reserpine in inhibiting DNA repair, cell proliferation, and invasion
TumCP↓,
TumCI↓,


Showing Research Papers: 1 to 7 of 7

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 7

Pathway results for Effect on Cancer / Diseased Cells:


NA, unassigned(tgid=0) ⓘ

ERCC4/XPF↓, 1,   Ku70/XRCC6↓, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

GPx4↓, 1,   NOX4↓, 1,   NRF2↝, 1,   ROS↓, 1,   ROS↑, 3,   SOD2↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

MEK↓, 1,   MMP↓, 3,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

12LOX↓, 1,   ERCC1↓, 1,   SIRT1↑, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 3,   APAF1↑, 1,   Apoptosis↑, 1,   BAD↓, 1,   BAX↑, 3,   Casp3↑, 3,   Casp8↑, 1,   Casp9↑, 3,   Cyt‑c↑, 2,   DR5↑, 1,   Fas↑, 1,   Mcl-1↓, 2,  

Kinase & Signal Transduction(tgid=6) ⓘ

HER2/EBBR2↓, 1,  

Protein Folding & ER Stress(tgid=8) ⓘ

ER Stress↓, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

TumAuto↑, 2,  

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↑, 1,   DNArepair↓, 1,   PARP↑, 1,   PCNA↓, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

cycD1/CCND1↓, 1,   TumCCA↑, 1,  

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

EMT↓, 2,   ERK↓, 1,   p‑ERK↓, 1,   FOXO3↑, 1,   mTOR↓, 3,   NOTCH1↓, 1,   PI3K↓, 2,  

Migration(tgid=13) ⓘ

Ca+2↑, 1,   FAK↓, 1,   Ki-67↓, 1,   MMP2↓, 2,   MMP9↓, 2,   SMAD2↓, 1,   p‑SMAD2↓, 3,   SMAD3↓, 3,   p‑SMAD3↓, 3,   SMAD4↓, 5,   p‑SMAD4↓, 2,   Snail↓, 1,   TGF-β↓, 6,   TGF-β↑, 1,   TumCI↓, 2,   TumCMig↓, 2,   TumCP↓, 2,   TumMeta↓, 2,  

Angiogenesis & Vasculature(tgid=14) ⓘ

ECM/TCF↓, 1,   HIF-1↓, 1,   Hif1a↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

CXCR4↓, 1,   IL6↓, 1,   NF-kB↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

ChemoSen↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

HER2/EBBR2↓, 1,   IL6↓, 1,   Ki-67↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1,  
Total Targets: 70

Pathway results for Effect on Normal Cells:


NA, unassigned(tgid=0) ⓘ

AntiBio↑, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 3,   GSTs↑, 1,   HO-1↑, 1,   NRF2↑, 1,   ROS↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1,   AntiTum↑, 1,   hepatoP↑, 1,   neuroP↑, 1,  
Total Targets: 10

Scientific Paper Hit Count for: SMAD4, SMAD family member 4
2 Baicalein
1 Andrographis
1 Ellagic acid
1 Gemcitabine (Gemzar)
1 EGCG (Epigallocatechin Gallate)
1 Emodin
1 Rauwolfia serpentina/Indian Snakeroot
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#:284  State#:%  Dir#:1
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