HMTs Cancer Research Results

HMTs, Histone methyltransferases (HMTs): Click to Expand ⟱
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Type:
Histone methyltransferases (HMTs) are enzymes that catalyze the addition of methyl groups to histones, leading to chromatin modifications that regulate gene expression. Altered expression and activity of various HMTs have been implicated in cancer initiation, progression, and response to therapy. However, given the diversity of HMT family members (e.g., EZH2, SETDB1, SUV39H1/2, DOT1L, MLL family members), the prognostic associations can vary considerably depending on the specific enzyme and cancer type.

– High levels of some HMTs (e.g., EZH2) are often linked to advanced disease stage and poorer survival
• Enzyme-Specific Effects: The prognostic value largely depends on which HMT is altered. For instance, while overexpression of EZH2 is commonly a marker of poor prognosis, some HMTs may act as tumor suppressors, and their loss could be associated with aggressive behavior.
Scientific Papers found: Click to Expand⟱
7181- CHA,    Chaetocin induces cell cycle arrest and apoptosis by regulating the ROS-mediated ASK-1/JNK signaling pathways
TumCCA↑, chaetocin was found to induce cell cycle arrest and oxidative stress, leading to CCLP-1 cell apoptosis.
ROS↑, Previous findings have revealed that chaetocin increases the level of ROS and induces cell apoptosis
ASK1↑, expression levels of the apoptosis signal-regulating kinase 1 (ASK-1) signalosome and its downstream c-Jun N-terminal kinase (JNK) signaling pathway were increased under oxidative stress stimulation.
JNK↑,
HMTs↓, chaetocin is an inhibitor of lysine-specific histone methyltransferases (HMTs), which are the key enzymes that mediate epigenetic control of gene expression.
Trx↓, Chaetocin is also an inhibitor of the redox enzyme thioredoxin reductase
tumCV↓, Chaetocin reduces the viability and invasive ability of the ICC cells.
TumCI↓,

7185- CHA,    Chaetocin-induced ROS-mediated apoptosis involves ATM–YAP1 axis and JNK-dependent inhibition of glucose metabolism
- vitro+vivo, GBM, A172 - in-vitro, GBM, T98G - in-vitro, GBM, U87MG
HMTs↓, Chaetocin, a histone methyltransferase inhibitor, is known to induce ROS generation.
ROS↑,
p‑ATM↑, Chaetocin-treated tumors exhibited heightened ROS, pATM, YAP1 and pJNK levels
YAP/TEAD↑, An increase in YAP1 level and decrease in YAP1 phosphorylation was observed upon Chaetocin treatment
p‑JNK↑,
TumPF↓, Chaetocin inhibits glioma cell proliferation
SUV39H↓, Chaetocin, an inhibitor of lysine-specific histone methyltransferase SUV39H1
TrxR↓, Chaetocin reduces thioredoxin reductase activity in a dose-dependent manner.
Casp3↑, Treatment with Chaetocin resulted in ∼3–5-fold increase in caspase-3 activity
Trx1↓, Chaetocin decreases the expression of TRX-1 in glioma cells
H3↓, Chaetocin-mediated inhibition of histone H3 methylation is ROS dependent
lactateProd↓, Chaetocin decreases lactate levels, ATP production and glucose uptake in a ROS- and JNK-dependent manner
ATP↓,
GlucoseCon↓,
TumCG↓, Chaetocin inhibits growth of tumor xenograft in nude mice
Dose↝, 10 animals each and were administered either with vehicle or Chaetocin (0.5 mg/kg body weight), intraperitoneally on alternate days for 25 days.

7167- CHA,    Chaetocin-induced ROS-mediated apoptosis involves ATM-YAP1 axis and JNK-dependent inhibition of glucose metabolism
- vitro+vivo, GBM, A172 - in-vitro, GBM, T98G - in-vitro, GBM, U87MG
HMTs↓, Chaetocin, a histone methyltransferase inhibitor, is known to induce ROS generation.
ROS↑,
YAP/TEAD↑, Increased intracellular ROS induced (i) Yes-associated protein 1 (YAP1) expression independent of the canonical Hippo pathway as well as (ii) ATM and JNK activation.
ATM↑,
JNK↑,
Apoptosis↑, Increased interaction of YAP1 with p73 and p300 induced apoptosis in an ATM-dependent manner.
GlucoseCon↓, decreased ATP production was accompanied by a ROS/JNK-dependent decrease in cellular glucose uptake by glioma cells in the presence of Chaetocin
lactateProd↓, A significant decrease in lactate production (Figure 5d) and ATP generation (Figure 5e) was observed in Chaetocin-treated cells as compared with the untreated control.
ATP↓,
TumCP↓, Chaetocin inhibits glioma cell proliferation
TrxR↓, Chaetocin treatment reduced thioredoxin reductase activity in a dose-dependent manner with ∼40% decrease in activity observed at 1 μM concentration
Trx1↓, Chaetocin decreases the expression of TRX-1 in glioma cells
H3K9↓, The decrease in H3K9me3 levels observed upon Chaetocin treatment was reverted in the presence of ROS inhibitor NAc
p‑ATM↑, Chaetocin induced an increase in pATM and γH2AX expression in a ROS-dependent manner
γH2AX↑,
ALDOB↑, ALDOB, ENO3, FBP1, FBP2 G6PC, GCK GSK3B, GYS2, HK3, PCK1, PGK2, PGM3, PHKG1, PKLR, PRPS1L1 and PYGM) were elevated by more than 2 fold upon Chaetocin treatment
ENO3↑,
FBP1↑,
GSK‐3β↑,
HK3↑,
PCK1↑,
PGK2↑,
PGM1↑,
PGM3↑,
PHKG1↑,
PKLR↑, PKLR, up-regulated by 20.9
HK2↓, HK2, downregulated by 4.5 fold
PCNA↓, Decrease in both PCNA-positive cells and its protein level in Chaetocin-treated tumors indicated inhibition of cell proliferation

1435- GEN,  SFN,    The Effects of Combinatorial Genistein and Sulforaphane in Breast Tumor Inhibition: Role in Epigenetic Regulation
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, MCF7
DNMTs↓, GEN extensively studied for its role as DNA methyltransferase (DNMT) inhibitor
HDAC↓, SFN), is known as a histone deacetylase (HDAC) inhibitor
eff↑, Our results indicate that the combination of GEN and SFN is much more effective than their single doses in increasing the rate of apoptosis
TumCCA↑, G2 phase in MDA-MB-231 and G1 phase in MCF-7
HMTs↓, histone methyltransferase (HMT) inhibitor
HDAC2↓, combination downregulates the levels of HDAC2 and HDAC3 both at the mRNA and protein levels
HDAC3↓,
KLF4↓, potential to downregulate KLF4 levels, which plays an important role in stem cell formation.
hTERT/TERT↓,

3359- QC,    Quercetin modifies 5′CpG promoter methylation and reactivates various tumor suppressor genes by modulating epigenetic marks in human cervical cancer cells
- in-vitro, Cerv, HeLa
DNMTs↓, When nuclear extracts were incubated with increasing doses of quercetin (25 and 50uM) they were found to inhibit the function of the DNMTs by 32% and 49% respectively, in comparison to untreated control
HDAC↓, quercetin (25 and 50 uM), they were found to inhibit the function of the HDACs by 47% and 62% in comparison to untreated control.
HMTs↓, quercetin (25 and 50 uM), were found to inhibit the function of the HMT H3K9 by 63% and 71%
DNMT3A↓, preferred binding of quercetin on DNMT3A and DNMT3B is within the substrate binding cavity and could competitively inhibit the protein
EZH2↓, Quercetin interacts with EZH2 and functions as an inhibitor
HDAC1↓, Quercetin was able to reduce the activity of class II HDACs significantly, with concomitant downregulation of HDAC1, HDAC2, HDAC6, HDAC7, and HDAC11 expression
HDAC2↓,
HDAC6↓,
HDAC11↓,
G9a↓, quercetin and this correlates well with the observed downregulation of G9A expression
TIMP3↑, Fig8: quercetin resulted in reduced promoter methylation of several TSGs (APC, CDH1, CDH13, DAPK1, FHIT, GSTP1, MGMT, MLH1, PTEN, RARB, RASSF1, SOC51, TIMP3, and VHL
PTEN↑,
SOCS1↑,

3360- QC,    Role of Flavonoids as Epigenetic Modulators in Cancer Prevention and Therapy
- Review, Var, NA
HDAC↓, Quercetin modulates the expression of various chromatin modifiers and declines the activity of HDACs, DNMTs and HMTs in a dose-dependent manner in human cervical cancer (HeLa) cells
DNMTs↓,
HMTs↓,
Let-7↑, Quercetin also induced let-7c which decreased pancreatic tumor growth by posttranscriptional activation of Numbl and indirect inhibition of Notch
NOTCH↓,


Showing Research Papers: 1 to 6 of 6

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 6

Pathway results for Effect on Cancer / Diseased Cells:


NA, unassigned(tgid=0) ⓘ

ALDOB↑, 1,   ENO3↑, 1,   H3K9↓, 1,   HK3↑, 1,   PGK2↑, 1,   PGM3↑, 1,   PHKG1↑, 1,   PKLR↑, 1,   SUV39H↓, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

ROS↑, 3,   Trx↓, 1,   Trx1↓, 2,   TrxR↓, 2,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↓, 2,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

FBP1↑, 1,   GlucoseCon↓, 2,   HK2↓, 1,   lactateProd↓, 2,   PCK1↑, 1,   PGM1↑, 1,  

Cell Death(tgid=5) ⓘ

Apoptosis↑, 1,   ASK1↑, 1,   Casp3↑, 1,   hTERT/TERT↓, 1,   JNK↑, 2,   p‑JNK↑, 1,   YAP/TEAD↑, 2,  

Transcription & Epigenetics(tgid=7) ⓘ

EZH2↓, 1,   H3↓, 1,   tumCV↓, 1,  

DNA Damage & Repair(tgid=10) ⓘ

ATM↑, 1,   p‑ATM↑, 2,   DNMT3A↓, 1,   DNMTs↓, 3,   G9a↓, 1,   PCNA↓, 1,   γH2AX↑, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

TumCCA↑, 2,  

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

GSK‐3β↑, 1,   HDAC↓, 3,   HDAC1↓, 1,   HDAC11↓, 1,   HDAC2↓, 2,   HDAC3↓, 1,   HDAC6↓, 1,   HMTs↓, 6,   KLF4↓, 1,   Let-7↑, 1,   NOTCH↓, 1,   PTEN↑, 1,   TumCG↓, 1,  

Migration(tgid=13) ⓘ

TIMP3↑, 1,   TumCI↓, 1,   TumCP↓, 1,   TumPF↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

SOCS1↑, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

Dose↝, 1,   eff↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

EZH2↓, 1,   hTERT/TERT↓, 1,  
Total Targets: 60

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: HMTs, Histone methyltransferases (HMTs)
3 chaetocin
2 Quercetin
1 Genistein (soy isoflavone)
1 Sulforaphane (mainly Broccoli)
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#:1096  State#:%  Dir#:1
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