H3K9 Cancer Research Results

H3K9, histone H3 lysine 9: Click to Expand ⟱
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H3K9 (histone H3 lysine 9) is a major regulatory residue on histone H3 that can undergo methylation or acetylation to alter chromatin structure and gene expression. Methylated H3K9, particularly H3K9me2 and H3K9me3, is generally associated with transcriptional repression and heterochromatin formation, whereas H3K9ac is associated with more transcriptionally active chromatin. In cancer, abnormal regulation of H3K9 modifications can contribute to silencing of tumour-suppressor genes, altered differentiation, stemness and treatment resistance. H3K9 should therefore be treated as an umbrella epigenetic target, with specific marks such as H3K9me3



Scientific Papers found: Click to Expand⟱
7179- CHA,    Chaetocin disrupts the SUV39H1–HP1 interaction independent of SUV39H1 methyltransferase activity
- in-vitro, NA, NA
H3K9↓, Chaetocin is a widely used chemical that decreases H3K9 methylation in cells
SUV39H↓, It is frequently attributed as a specific inhibitor of the histone methyltransferase activities of SUV39H1/SU(VAR)3–9,

7183- CHA,    The SUV39H1 inhibitor chaetocin induces differentiation and shows synergistic cytotoxicity with other epigenetic drugs in acute myeloid leukemia cells
- in-vitro, AML, HL-60 - in-vitro, AML, KG-1 - in-vitro, lymphoma, U937
TumCD↓, The SUV39H1 inhibitor (chaetocin) and the G9a inhibitor (UNC0638) caused cell death in AML cells at high concentrations.
SUV39H↓,
CD11b↑, only chaetocin-induced CD11b expression and differentiation of AML cells at non-cytotoxic concentration.
Diff↑,
H3K9↓, Long-term incubation of chaetocin led to downregulation of SUV39H1 and reduction of H3K9 tri-methylation in HL-60 and KG-1a cells.
eff↑, Combination of chaetocin with suberoylanilide hydroxamic acid (SAHA, a histone deacetylase inhibitor) or JQ (a BET (bromodomain extra terminal) bromodomain inhibitor) showed synergistic cytotoxicity.

7186- CHA,  TSA,    Improved Therapeutic Effect against Leukemia by a Combination of the Histone Methyltransferase Inhibitor Chaetocin and the Histone Deacetylase Inhibitor Trichostatin A
- in-vitro, AML, NA
SUV39H↓, Chaetocin specifically inhibits SUV39H1, resulted in H3K9 methylation reduction as well as reactivation of silenced genes in cancer cells.
H3K9↓,
eff↑, Co-treatment with chaetocin and HDAC inhibitor trichostatin A (TSA) dramatically increased apoptosis and produced greater activation of genes.

7171- CHA,    Chaetocin-mediated SUV39H1 inhibition targets stemness and oncogenic networks of diffuse midline gliomas and synergizes with ONC201
- vitro+vivo, GBM, DIPG
TumCG↓, High-throughput small-molecule screening identified an epigenetic compound chaetocin as a potent blocker of DIPG cell growth
TumCP↓, Chaetocin treatment selectively decreased proliferation and increased apoptosis of DIPG cells and significantly extended survival in DIPG xenograft models, while restoring H3K27me3 levels
Apoptosis↓,
OS↑,
H3K9↓, he loss of H3K9 methyltransferase SUV39H1 inhibited DIPG cell growth.
SUV39H↓, SUV39H1 and H3K9me3 Levels Are Downregulated by Chaetocin Treatment
eff↑, Consistently, a combination of chaetocin treatment with a DRD2 antagonist ONC201 synergistically increased the antitumor efficacy.
CSCs↓, SUV39H1 Inhibition Decreases Stemness and Oncogenic Signaling
SOX9↓, chaetocin treatment and SUV39H1 depletion led to decreased expression of genes associated with stemness (eg, SOX9, MYCN, OLIG2, AURKB), growth factor signaling (eg, HGF, FGF21), receptor-tyrosine kinases signaling (eg, EGFR, FGFR, and PDGFR), and WNT
HGF/c-Met↓,
FGF21↓,
EGFR↓,
PDGFR-BB↓,
Wnt↓,
MYCN↑,
OLIG2↓,
AURKB↓,
HO-1↑, genes associated with the NRF2 stress pathway, oxidative stress-related genes (eg, HMOX1, ARK1C1), cell cycle inhibition (eg, CDKN1A, CDKN2B, CDKN2D), and neuronal signaling activity (eg, DRD2, NRG1, NRXN1) were upregulated
P21↑,

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

7162- CHA,    Chaetocin disrupts the SUV39H1-HP1 interaction independent of SUV39H1 methyltransferase activity
- Study, Nor, NA
*H3K9↓, Chaetocin is a widely used chemical that decreases H3K9 methylation in cells.
*other↓, hypothesis that chaetocin may have an additional downstream impact aside from inhibition of methyltransferase activity.
*SUV39H↓, Chaetocin inhibits the interaction between SUV39H1 and HP1

7161- CHA,    Chaetocin is a nonspecific inhibitor of histone lysine methyltransferases
- Review, Var, NA
H3K9↓, chaetocin is a ‘specific’ inhibitor of the H3K9 HKMT SU(VAR)3-9,
HKMT↓,
SUV39H↓,
Dose↝, Chaetocin (1)7 was indeed found to have in vitro inhibitory activity (IC50 = 0.11 mM; Fig. 1b) on purified human SUV39H1, in agreement with the data of Greiner et al.3 (IC50 = 0.8 mM).


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) ⓘ

ALDOB↑, 1,   AURKB↓, 1,   ENO3↑, 1,   H3K9↓, 6,   HK3↑, 1,   HKMT↓, 1,   MYCN↑, 1,   OLIG2↓, 1,   PGK2↑, 1,   PGM3↑, 1,   PHKG1↑, 1,   PKLR↑, 1,   SUV39H↓, 5,  

Redox & Oxidative Stress(tgid=1) ⓘ

HO-1↑, 1,   ROS↑, 1,   Trx1↓, 1,   TrxR↓, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

FBP1↑, 1,   FGF21↓, 1,   GlucoseCon↓, 1,   HK2↓, 1,   lactateProd↓, 1,   PCK1↑, 1,   PGM1↑, 1,  

Cell Death(tgid=5) ⓘ

Apoptosis↓, 1,   Apoptosis↑, 1,   HGF/c-Met↓, 1,   JNK↑, 1,   TumCD↓, 1,   YAP/TEAD↑, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

SOX9↓, 1,  

DNA Damage & Repair(tgid=10) ⓘ

ATM↑, 1,   p‑ATM↑, 1,   PCNA↓, 1,   γH2AX↑, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

P21↑, 1,  

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

CSCs↓, 1,   Diff↑, 1,   GSK‐3β↑, 1,   HMTs↓, 1,   TumCG↓, 1,   Wnt↓, 1,  

Migration(tgid=13) ⓘ

CD11b↑, 1,   TumCP↓, 2,  

Angiogenesis & Vasculature(tgid=14) ⓘ

EGFR↓, 1,   PDGFR-BB↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

Dose↝, 1,   eff↑, 3,  

Clinical Biomarkers(tgid=22) ⓘ

EGFR↓, 1,  

Functional Outcomes(tgid=23) ⓘ

OS↑, 1,  
Total Targets: 51

Pathway results for Effect on Normal Cells:


NA, unassigned(tgid=0) ⓘ

H3K9↓, 1,   SUV39H↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

other↓, 1,  
Total Targets: 3

Scientific Paper Hit Count for: H3K9, histone H3 lysine 9
7 chaetocin
1 Trichostatin A
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

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