MKK4 Cancer Research Results

MKK4, Mitogen-Activated Protein Kinase Kinase 4: Click to Expand ⟱
Source:
Type:
MKK4 (Mitogen-Activated Protein Kinase Kinase 4), also known as MAP2K4 or SEK1, is a dual-specificity kinase that plays a role in activating the stress-activated protein kinases (SAPKs) including the Jun N-terminal Kinases (JNKs) and p38 pathways. These signaling cascades are involved in cellular responses to stress, inflammation, and apoptosis.

In some contexts, MKK4 is considered a tumor suppressor since its activation may trigger apoptosis or cell-cycle arrest in response to oncogenic stress.
However, there are instances where increased MKK4 activity is associated with cancer progression, potentially through its roles in cell migration or by promoting a tumor-promoting inflammatory microenvironment.
Scientific Papers found: Click to Expand⟱
8236- LE,    Licorice (Glycyrrhiza glabra L.)-Derived Phytochemicals Target Multiple Signaling Pathways to Confer Oncopreventive and Oncotherapeutic Effects
- Review, Var, NA
Bcl-2↓, Multiple licorice constituents have been shown to bind to and inhibit the activities of various cellular targets, including B-cell lymphoma 2, cyclin-dependent kinase 2, phosphatidylinositol 3-kinase, c-Jun N-terminal kinases, mammalian target of rap
CDK2↓,
PI3K↓,
cJun↓,
mTOR↓,
NF-kB↓, nuclear factor-κB, signal transducer and activator of transcription 3, vascular endothelial growth factor, and matrix metalloproteinase-3, resulting in reduced carcinogenesis in several in vitro and in vivo models with no evident toxicity
VEGF↓,
MMP3↓,
toxicity↓,
Dose↑, European Union established a temporary upper limit of 100 mg/day for glycyrrhizin consumption (about the amount found in 60–70 g licorice).
chemoP↑, Licorice has long been used as an antidote to counteract the toxicity of chemotherapeutic treatment
*antiOx↑, including antioxidant and anti-inflammatory properties, as well as a protective effect on several organs
*Inflam↓,
Dose↝, The main sweet-tasting ingredient of G. glabra (licorice) root is glycyrrhizin (or glycyrrhizinic acid or GA).
*COX2/PTGS2↓, glycyrrhizin and 18β-glycyrrhetinic acid have been defined by different investigators as significant inhibitors of inflammatory factors, such as cyclooxygenase-2 (COX-2), HMGP 1, inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), IL-10, t
*iNOS↓,
*IL6↓,
*IL10↓,
*PGE2↓, licochalcone A and licochalcone B inhibit IL-6 and PGE2 in LPS-induced macrophage cells,
*IκB?, isoliquiritigenin and isoliquiritin inhibit inhibitory κBα (IκBα) phosphorylation and degradation, and increase the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 in LPS-induced macrophage cells
*NRF2↑,
*HO-1↑,
*lipid-P↓, figure 2
*ROS↓,
*Catalase↑,
*GPx↑,
*SOD↑,
Apoptosis↑, The glycyrrhetinic acid and its derivatives induce mitochondrial-mediated apoptosis in cancer cells, as it was found in a study conducted by Lin et al119 where apoptosis was induced by the generation of reactive oxygen species (ROS)
ROS↑,
TumCP↓, GA, another flavonoid extracted from the roots of licorice also induces apoptosis and suppresses the proliferation of MDA-MB-231 breast cancer cells by increased generation of ROS.123
TumCCA↑, GA induces cell cycle arrest at G1/S phase in gastric cancer cells by downregulating the cyclin E1, cyclin E2, and cyclin D1-3 levels causing cell death in these cancer cells.
cycE/CCNE↓,
cycD1/CCND1↓,
p‑GSK‐3β↓, SK-MEL-28 and SK-MEL-5 Induced apoptosis ↓G1 phase, ↓cyclin D1, ↓cyclin E, ↓p-Akt, ↓p-GSK3β, ↓p-JNK1/2, ↓PI3K, ↓MKK4, ↓MKK7
PI3K↓,
MKK4↓,
MKK7↓,
HSP90↓, HT-29 Induced apoptosis ↓Proliferation, ↓viability of cells, ↑cell death of cancer cells, ↓HSP90
LC3‑Ⅱ/LC3‑Ⅰ↑, MKN28 Inhibited metastasis ↓Proliferation and metastasis, ↓migration and invasion, ↑LC3II/LC3I ratio, ↑Beclin 1, ↓p62, ↓p-Akt, ↓p- mTOR
Beclin-1/ATG6↑,
p62↓,
p‑Akt↓,
cl‑Casp9↑, Caki Induced apoptosis ↑Cleavage of caspase-9, caspase-7 and caspase-3, and PARP, ↑Bax, ↓Bcl-2, ↓ Bcl-xL, ↑cyt. c release, ↑p53, ↓MDM2, ↑ROS levels, ↓STAT3, ↓cyclin D1 and D2, ↓p-JAK2,
cl‑Casp7↑,
cl‑Casp3↑,
cl‑PARP↑,
BAX↑,
Cyt‑c↑,
P53↑,
STAT3↓,
E-cadherin↑, ↑E-cadherin ↓Vimentin, ↓N-cadherin,
Vim↓,
N-cadherin↓,
CD31/PECAM-1↓, ↓VEGF-A, ↓CD31 ↓HIF-1α, ↓iNOS, ↓COX-2
Hif1a↓,
iNOS↓,
DNAdam↑, ↑Nuclear condensation, ↑ nuclear fragmentation, ↑ apoptotic ratio, ↑decrease in the ΔΨ m, ↑Bax, ↑ Bim, ↑Apaf-1, ↑caspase-9, ↑caspase-3, ↓Bcl-2, ↑CDK2
MMP↓,
BIM↑,
APAF1↑,
PCNA↓, ↓PCNA, ↓MMP2, ↓ MMP9, ↑caspase-3, ↓p-PI3K, ↓p-Akt
toxicity↝, In addition, based on a case report, excessive consumption of licorice may also lead to toxic consequences in the form of thrombocytopenia.
eff↑, A clinical stage II preliminary trial revealed that licorice root extract in combination with docetaxel works in treating patients with hormonal therapy resistant metastatic prostate tumors

1141- Myr,    Myricetin: targeting signaling networks in cancer and its implication in chemotherapy
- Review, NA, NA
*PI3K↑, apoptotic potential of myricetin is specific for affected cells. In healthy cells, it activates PI3K/Akt signaling and inhibits ERK/JNK pathway to induce cytoprotective influence
*Akt↑,
p‑Akt↓,
SIRT3↑,
p‑ERK↓,
p38↓,
VEGF↓,
MEK↓, MEK1
MKK4↓,
MMP9↓,
Raf↓,
F-actin↓,
MMP2↓,
COX2/PTGS2↓,
BMP2↓,
cycD1/CCND1↓,
Bax:Bcl2↑,
EMT↓,
EGFR↓,
TumAuto↑,


Showing Research Papers: 1 to 2 of 2

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

ROS↑, 1,   SIRT3↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

MEK↓, 1,   MKK4↓, 2,   MKK7↓, 1,   MMP↓, 1,   Raf↓, 1,  

Cell Death(tgid=5) ⓘ

p‑Akt↓, 2,   APAF1↑, 1,   Apoptosis↑, 1,   BAX↑, 1,   Bax:Bcl2↑, 1,   Bcl-2↓, 1,   BIM↑, 1,   BMP2↓, 1,   cl‑Casp3↑, 1,   cl‑Casp7↑, 1,   cl‑Casp9↑, 1,   Cyt‑c↑, 1,   iNOS↓, 1,   p38↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

cJun↓, 1,  

Protein Folding & ER Stress(tgid=8) ⓘ

HSP90↓, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

Beclin-1/ATG6↑, 1,   LC3‑Ⅱ/LC3‑Ⅰ↑, 1,   p62↓, 1,   TumAuto↑, 1,  

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↑, 1,   P53↑, 1,   cl‑PARP↑, 1,   PCNA↓, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

CDK2↓, 1,   cycD1/CCND1↓, 2,   cycE/CCNE↓, 1,   TumCCA↑, 1,  

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

EMT↓, 1,   p‑ERK↓, 1,   p‑GSK‐3β↓, 1,   mTOR↓, 1,   PI3K↓, 2,   STAT3↓, 1,  

Migration(tgid=13) ⓘ

CD31/PECAM-1↓, 1,   E-cadherin↑, 1,   F-actin↓, 1,   MMP2↓, 1,   MMP3↓, 1,   MMP9↓, 1,   N-cadherin↓, 1,   TumCP↓, 1,   Vim↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

EGFR↓, 1,   Hif1a↓, 1,   VEGF↓, 2,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 1,   NF-kB↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

Dose↑, 1,   Dose↝, 1,   eff↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

EGFR↓, 1,  

Functional Outcomes(tgid=23) ⓘ

chemoP↑, 1,   toxicity↓, 1,   toxicity↝, 1,  
Total Targets: 62

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1,   Catalase↑, 1,   GPx↑, 1,   HO-1↑, 1,   lipid-P↓, 1,   NRF2↑, 1,   ROS↓, 1,   SOD↑, 1,  

Cell Death(tgid=5) ⓘ

Akt↑, 1,   iNOS↓, 1,  

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

PI3K↑, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 1,   IL10↓, 1,   IL6↓, 1,   Inflam↓, 1,   IκB?, 1,   PGE2↓, 1,  

Clinical Biomarkers(tgid=22) ⓘ

IL6↓, 1,  
Total Targets: 18

Scientific Paper Hit Count for: MKK4, Mitogen-Activated Protein Kinase Kinase 4
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#:1017  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

 

Home Page