SUV39H Cancer Research Results

SUV39H, suppressor of variegation 3-9 homolog: Click to Expand ⟱
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SUV39H1/KMT1A (suppressor of variegation 3-9 homolog 1; H3K9 histone methyltransferase) is a SET-domain lysine methyltransferase that catalyzes methylation of histone H3 lysine 9, particularly formation of H3K9me3, a repressive chromatin mark associated with heterochromatin and transcriptional silencing. SUV39H1 regulates chromatin organization, genome stability, cellular differentiation, senescence and gene expression. In several cancers, increased SUV39H1 activity can promote epigenetic silencing of tumour-suppressive genes, stemness, proliferation and treatment resistance, although its role can vary by tumour context. In such settings, the cancer-associated direction is commonly up and the desired anticancer modulation is down or methyltransferase inhibition.



Scientific Papers found: Click to Expand⟱
7174- CHA,    Inhibition of SUV39H1 reduces tumor angiogenesis via Notch1 in oral squamous cell carcinoma
- vitro+vivo, OS, OS-RC-2
SUV39H↓, The effect of SUV39H1 inhibition on OSCC was investigated in vivo by chaetocin treatment.
TumCG↓, In vivo experiment chaetocin treatment significantly inhibit the growth of tumor, and reduce SUV39H1, Notch1, CD31 expression.
NOTCH1↓,
CD31↓,
VEGF↓, lead to the decreased expression of Notch1 and VEGF proteins, as well as the decreased migration and tube formation ability of vascular endothelial cells
toxicity↓, Treatment doses of Chaetocin has no obvious toxicity in mice
Ki-67↓, groups treated Chaetocin, SUV39H1, Notch1, CD31, Ki67 staining intensity is lower than the control group
angioG↓, These results further suggest that inhibition of SUV39H1 may reduce tumor angiogenesis.

7175- CHA,    Chaetocin from Chaetomium minutum
- Review, Var, NA
TrxR1↓, Chaetocin is a selective competitive inhibitor of thioredoxin reductase-1 (TrxR1), a putative mechanism of its anticancer activity.
SUV39H↓, Chaetocin is a competitive inhibitor for S-adenosylmethionine. The specificity of chaetocin for SU(VAR)3-9 makes this compound an excellent tool for the study of heterochromatin-mediated gene repression.

7178- CHA,    SUV39H1 Regulates Gastric Cancer Progression via the H3K9me3/ALDOB Axis
- in-vitro, GC, NA
tumCV↓, The treatment of chaetocin or F5446 (inhibitors of SUV39H1 enzymatic activity) also restrained GC cell behaviors.
TumCG↓, Furthermore, tumor growth of mice was suppressed by sh-SUV39H1 transfection, chaetocin treatment, or F5446 treatment. In conclusion, SUV39H1 promoted GC progression by modulating the H3K9me3/ALDOB axis.
SUV39H↓,

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,

7180- CHA,    Chaetocin: A review of its anticancer potentials and mechanisms
- Review, Var, NA
TumCG↓, . Several studies have demonstrated that chaetocin suppresses the growth and proliferation of various tumour cells by regulating multiple signalling pathways related
TumCP↓,
Apoptosis↑, inducing cancer cell apoptosis (intrinsic and extrinsic), enhancing autophagy, inducing cell cycle arrest, and inhibiting tumour angiogenesis, invasion, and migration.
TumCCA↑,
angioG↓,
TumCI↓,
TumCMig↓,
SUV39H↓, chaetocin inhibits the activities of histone lysine methyltransferase SUV39H1
TrxR↓, formed covalent adducts with numerous proteins, including the thioredoxin-thioredoxin reductase (Trx-TrxR) system, hypoxia inducible factor-1 alpha (HIF-1α), heat shock protein 90 (Hsp90)
Hif1a↓,
HSP90↓,
ox-Trx1↑, ↑ oxidized TRX-1 & ROS activation; ↓ PI3K/AKT pathway & p-AKT; ↑ caspase-3, caspase-8 & caspase-9 activation; ↑ cleaved PARP proteins; ↓ BCL-2, BCL-XL, MCL-1, XIAP
ROS↑,
PI3K↓,
Akt↓,
Casp3↑,
Casp8↑,
Casp9↑,
cl‑PARP↑,
Bcl-2↓,
Bcl-xL↓,
Mcl-1↓,
XIAP↓,
DR5↑, ↑ DR5 & CHOP, ATF3;
CHOP/DDIT3↑,
ATF3↑,
angioG↓, chaetocin also indirectly targets tumour cells by inducing antiangiogenic effects in the tumour microvasculature.
VEGF↑, robust decrease in secreted VEGF in the culture media of treated cells and subsequent downregulation of the target genes of VEGFA, LDHA, ENO1 and HZF-1,
LDHA↓,
ENO1↓,

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.

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.

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↑,

7170- CHA,    Chaetocin Abrogates the Self-Renewal of Bladder Cancer Stem Cells via the Suppression of the KMT1A–GATA3–STAT3 Circuit
- in-vivo, Bladder, NA
TumCP↓, chaetocin significantly suppressed the cell propagation (inhibition ratio: 65%–88%, IC50 = 24.4–32.5 nM), induced apoptosis (2–5-fold), and caused G1 phase cell cycle arrest (68.9 vs 55.5%) of bladder cancer (BC) cells,
TumCCA↑,
selectivity↑, without influencing normal bladder epithelial cells.
CSCs↓, chaetocin abrogated the self-renewal of BCSCs (inhibition ratio: 80.1%) via the suppression of the KMT1A–GATA3–STAT3 circuit and other stemness-related pathways.
SUV39H↓,
GATA3↓,
STAT3↓,
TumCG↓, intravesical instillation of chaetocin remarkably inhibited the growth of xenograft tumors (inhibition ratio: 71–82%) and prolonged the survival of tumor-bearing mice (70 vs 53 days).
OS↑,

7168- CHA,    The anticancer effect of chaetocin is enhanced by inhibition of autophagy
- vitro+vivo, Liver, HepG2 - in-vitro, Liver, HepG3 - in-vitro, Liver, HUH7
Apoptosis↓, we show that chaetocin is able to induce both apoptosis and autophagy in several hepatoma cell lines including HepG2, Hep3B and Huh7 cell lines.
TumAuto↑,
ROS↑, It was discovered as a potent and selective anti-myeloma agent as it induced cellular oxidative stress
Hif1a↓, chaetocin has received further attention as it was able to inhibit HIF-1α signaling
SUV39H↓, inhibiting histone lysine methyltransferase SU(VAR)3-9
cl‑PARP↑, Chaetocin caused a significant increase in cleavage of PARP
eff↑, Suppression of autophagy enhances chaetocin-induced cell death
eff↑, apoptosis enhancement by Baf.A1 in chaetocin-treated cells was due to the blocking of autophagy.

7166- CHA,    Anti-leukemia activity of chaetocin via death receptor-dependent apoptosis and dual modulation of the histone methyl-transferase SUV39H1
- vitro+vivo, AML, U937
SUV39H↓, We report here that pharmacological inhibition of SUV39H1 by chaetocin induces apoptosis in leukemia cell lines in vitro and primary AML cells ex vivo, and that it interferes with leukemia growth in vivo.
Apoptosis↑,
ROS↑, Chaetocin treatment upregulates reactive oxygen species (ROS) production as well as the transcription of death-receptor-related genes, in a ROS-dependent manner, leading to death receptor-dependent apoptosis.
TumCCA↑, Chaetocin treatment resulted in cell cycle arrest in the S phase (Figure 1c), and dose-dependent impairment of cell viability
tumCV↓,
Casp3↑, chaetocin also activated caspase-3/7 activity in other leukemia cell lines (for example, HL60 and NB4;
Casp9↑,
Fas↑, 100 nM chaetocin treatment induced and/or upregulated death receptor signaling molecule mRNAs, such as that of Fas, FasL, TNF-related apoptosis-induced ligand, DR4 and TL1A, as well as of the cell cycle inhibitor p21/WAF1
FasL↑,
DR4↑,
P21↑,
eff↓, Co-treatment with L -NAC inhibited chaetocin-induced upregulation of mRNA encoding for p21/WAF1, death receptors and ligands
eff↑, he anti-leukemic action of chaetocin was potentiated by both Vorinostat (Figure 7a; for a review see Marks and Breslow 26 ), a potent HDACi, a

7163- CHA,    The anticancer effects of chaetocin are independent of programmed cell death and hypoxia, and are associated with inhibition of endothelial cell proliferation
- in-vitro, Lung, A549 - in-vitro, OS, U2OS - in-vitro, CRC, HCT116 - in-vitro, CRC, HeLa - in-vivo, Ovarian, SKOV3
ROS↑, We previously reported that chaetocin has potent and selective anti-myeloma activity attributable to reactive oxygen species (ROS) induction imposed by inhibition of the redox enzyme thioredoxin reductase
Trx↓,
Apoptosis↑, Chaetocin induced ROS, oxidative damage to cellular proteins and apoptosis, with 2–10 nM IC50s (24 h exposures) in all tested solid tumour cell lines.
TumCG↓, Moreover, chaetocin inhibited SKOV3 ovarian cancer xenografts producing less vascular tumours, and inhibited human umbilical vein endothelial cell proliferation.
SUV39H↓, Chaetocin has also been found by others to inhibit histone methyltransferase SU(VAR)3–9 (Greiner et al, 2005) and HIF-1a signalling (
Hif1a↓,
TumCP↓, Chaetocin potently inhibits proliferation and colony formation in a broad range of cancer cell lines
eff↓, Consistent with prior observations in myeloma cells and cell lines (Isham et al, 2007) glutathione (GSH) or its cell permeable precursor NAC dramatically attenuated chaetocin-induced (i) reduction in colony formation
MMP↓, Chaetocin-induced mitochondrial membrane depolarisation and apoptosis
TumCG↓, Chaetocin attenuates the growth of SKOV3 ovarian cancer xenografts in nude mice
Dose↝, maximally tolerated IP dosing as 0.2 mg kg−1 5 × per week in mice.
toxicity↓, with minimal evidence of toxicities observed in treated animals.

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).

7169- HDN-1,  CHA,    Identification of epipolythiodioxopiperazines HDN-1 and chaetocin as novel inhibitor of heat shock protein 90
- in-vitro, Lung, H1975 - in-vitro, Lung, HCC827 - in-vitro, Lung, A549
HSP90↓, These results indicate that HDN-1 and chaetocin are inhibitors of Hsp90 and that SUV39H1 is a novel client protein of Hsp90.
TumCP↓, H1975, HCC827 and A549. HDN-1 inhibited the proliferation of these cancer cell lines with an IC50 of 0.22, 0.54, and 1.06 μM,
EGFR↓, We found that HDN-1 treatment reduced the expression levels of EGFR, Stat3, Akt, and Erk, and their active phosphorylated forms and downregulated the expression of Raf and Cyclin D1
STAT3↓,
Akt↓,
ERK↓,
Raf↓,
cycD1/CCND1↓,
SUV39H↓, HDN-1 is an analogue of chaetocin (Figure 6A), which is a fungal mycotoxin with histone methyltransferase SUV39H1 inhibitory activity


Showing Research Papers: 1 to 16 of 16

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 16

Pathway results for Effect on Cancer / Diseased Cells:


NA, unassigned(tgid=0) ⓘ

AURKB↓, 1,   H3K9↓, 5,   HKMT↓, 1,   MYCN↑, 1,   OLIG2↓, 1,   SUV39H↓, 15,  

Redox & Oxidative Stress(tgid=1) ⓘ

ATF3↑, 1,   HO-1↑, 1,   ROS↑, 5,   Trx↓, 1,   Trx1↓, 1,   ox-Trx1↑, 1,   TrxR↓, 2,   TrxR1↓, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↓, 1,   MMP↓, 1,   Raf↓, 1,   XIAP↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ENO1↓, 1,   FGF21↓, 1,   GlucoseCon↓, 1,   lactateProd↓, 1,   LDHA↓, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 2,   Apoptosis↓, 2,   Apoptosis↑, 3,   Bcl-2↓, 1,   Bcl-xL↓, 1,   Casp3↑, 3,   Casp8↑, 1,   Casp9↑, 2,   DR4↑, 1,   DR5↑, 1,   Fas↑, 1,   FasL↑, 1,   HGF/c-Met↓, 1,   p‑JNK↑, 1,   Mcl-1↓, 1,   TumCD↓, 1,   YAP/TEAD↑, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

SOX9↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

H3↓, 1,   tumCV↓, 2,  

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP/DDIT3↑, 1,   HSP90↓, 2,  

Autophagy & Lysosomes(tgid=9) ⓘ

TumAuto↑, 1,  

DNA Damage & Repair(tgid=10) ⓘ

p‑ATM↑, 1,   cl‑PARP↑, 2,  

Cell Cycle & Senescence(tgid=11) ⓘ

cycD1/CCND1↓, 1,   P21↑, 2,   TumCCA↑, 3,  

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

CSCs↓, 2,   Diff↑, 1,   ERK↓, 1,   GATA3↓, 1,   HMTs↓, 1,   NOTCH1↓, 1,   PI3K↓, 1,   STAT3↓, 2,   TumCG↓, 8,   Wnt↓, 1,  

Migration(tgid=13) ⓘ

CD11b↑, 1,   CD31↓, 1,   Ki-67↓, 1,   TumCI↓, 1,   TumCMig↓, 1,   TumCP↓, 5,   TumPF↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 3,   EGFR↓, 2,   Hif1a↓, 3,   PDGFR-BB↓, 1,   VEGF↓, 1,   VEGF↑, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

Dose↝, 3,   eff↓, 2,   eff↑, 6,   selectivity↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

EGFR↓, 2,   Ki-67↓, 1,  

Functional Outcomes(tgid=23) ⓘ

OS↑, 2,   toxicity↓, 2,  
Total Targets: 82

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: SUV39H, suppressor of variegation 3-9 homolog
16 chaetocin
1 Trichostatin A
1 epipolythiodioxopiperazine / epipolythiopiperazine-2,5-dione
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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