chaetocin / ROS Cancer Research Results

CHA, chaetocin: Click to Expand ⟱

Features:

Chaetocin is a fungal secondary metabolite of the epipolythiodioxopiperazine (ETP) class, originally isolated from Chaetomium species. It has potent preclinical anticancer activity through several mechanisms, including inhibition of histone H3K9 methyltransferases such as SUV39H1, reduction of H3K9me3, disruption of thioredoxin/thioredoxin-reductase redox signalling, induction of oxidative stress, inhibition of Hsp90-associated signalling and promotion of apoptosis. Chaetocin can suppress tumour-cell proliferation and stemness and has shown activity in leukemia, glioblastoma, diffuse midline glioma and several solid-tumour models. It can also sensitize cancer cells to apoptosis-inducing agents and radiation. Although frequently described as an SUV39H1 inhibitor, chaetocin is not highly target-selective and its anticancer effects should not be attributed solely to SUV39H1 inhibition. Chaetocin is an experimental fungal metabolite / epigenetic and redox-active anticancer compound, with current therapeutic evidence predominantly preclinical.

Chaetocin — a sulfur-rich fungal secondary metabolite of the epipolythiodioxopiperazine (ETP) class originally isolated from Chaetomium species. It is an experimental redox-active and epigenetically active small molecule with potent preclinical anticancer activity. Chaetocin is commonly described as an SUV39H1/KMT1A inhibitor, but this classification is incomplete: it inhibits thioredoxin reductase, produces substantial oxidative stress, covalently perturbs proteins through its reactive disulfide functionality, inhibits multiple histone lysine methyltransferases, disrupts the SUV39H1–HP1 interaction, and can inhibit Hsp90-dependent signaling. It should therefore be classified as a multitarget ETP fungal metabolite / experimental epigenetic-redox anticancer compound rather than as a selective SUV39H1 inhibitor.

Primary mechanisms (ranked):

Thioredoxin reductase / thioredoxin disruption and oxidative stress: inhibition and substrate competition at TrxR1 impair thioredoxin-dependent ROS detoxification, producing sustained oxidative stress that is strongly linked to chaetocin cytotoxicity.
SUV39H1 / H3K9me3 epigenetic disruption: decreases SUV39H1-associated H3K9 trimethylation and alters heterochromatin-dependent transcription; however, chaetocin is not a selective SUV39H1 catalytic inhibitor and can affect other histone lysine methyltransferases.
SUV39H1–HP1 heterochromatin disruption: the ETP disulfide functionality can covalently modify the SUV39H1 chromodomain and interfere with its interaction with HP1 independently of methyltransferase inhibition.
ROS-dependent apoptosis and DNA-damage signaling: activates intrinsic mitochondrial apoptosis, death-receptor signaling, ATM/YAP1/p73 pathways and caspases, with several models showing antioxidant-sensitive cytotoxicity.
PI3K/AKT and prosurvival signaling suppression: ROS-dependent inhibition of PI3K/AKT contributes to apoptosis and growth inhibition in several cancer models.
Hsp90 / proteostasis disruption: binds Hsp90 and promotes loss of multiple Hsp90 client proteins, including SUV39H1 and oncogenic signaling proteins.
Cancer stemness and transcriptional-network suppression: disrupts SUV39H1-dependent stem-cell programs including GATA3/STAT3 signaling in bladder cancer and stemness/growth-factor networks in glioma and diffuse midline glioma.
Metabolic suppression: ROS/JNK signaling can decrease glucose uptake, glycolytic enzyme activity, lactate production and cellular ATP generation in glioma models.
Antiangiogenic effects: inhibits endothelial-cell proliferation and can decrease tumor vascularization; SUV39H1/Notch1/VEGF modulation may contribute in some tumor models.

Bioavailability / PK relevance: Human pharmacokinetic parameters, therapeutic plasma concentrations, bioavailability and exposure-response relationships have not been established. Preclinical work indicates unusual intracellular handling related to the intact ETP disulfide groups and cellular redox environment. The highly reactive disulfide pharmacophore, broad protein reactivity and absence of validated human PK are major translational constraints.

In-vitro vs systemic exposure relevance: Anticancer potency varies substantially among models, ranging from low-nanomolar effects in some tumor screens to micromolar concentrations in other mechanistic experiments. There is no established human systemic exposure against which these concentrations can be compared. Consequently, even very potent in-vitro observations cannot currently be assumed to represent clinically achievable selective exposure. Normal-cell sparing has been observed in some hematologic and epithelial comparisons, but chaetocin also inhibits normal endothelial-cell proliferation, so tumor selectivity is not established as a general property.

Clinical evidence status: Preclinical only. Evidence includes cancer-cell studies, primary patient-derived cells, xenografts and other animal tumor models, with recent work supporting activity in glioblastoma, diffuse midline glioma and cancer stem-cell models. No established human therapeutic trials, randomized clinical evidence or approved adjunct use were identified. Chaetocin remains an experimental research compound and is not an approved anticancer drug.

Chaetocin Mechanistic Profile

Rank	Pathway / Axis	Cancer Cells	Normal Cells	TSF	Primary Effect	Notes / Interpretation
1	Thioredoxin reductase / Thioredoxin redox system	TrxR1↓; reduced Trx recycling	Potential TrxR inhibition; sensitivity appears lower in some normal-cell models	P/R	Loss of antioxidant capacity	One of the strongest mechanistically supported direct activities. Chaetocin acts as a competitive TrxR1 substrate/inhibitor rather than merely producing nonspecific ROS.
2	Oxidative stress / ROS accumulation	ROS↑	ROS effects possible; magnitude and tolerance are cell-dependent	P/R	Oxidative injury and cytotoxic signaling	Central anticancer mechanism across myeloma, leukemia, melanoma, gastric cancer, glioma and other models. Antioxidant rescue experiments frequently reduce cytotoxicity.
3	SUV39H1 / H3K9me3 chromatin axis	SUV39H1↓; H3K9me3↓	SUV39H1/H3K9me3↓ possible	R/G	Chromatin and transcriptional reprogramming	Important but should not be described as highly selective. Chaetocin inhibits multiple lysine methyltransferases and can affect SUV39H1 abundance as well as enzymatic function.
4	SUV39H1 / HP1 heterochromatin interaction	SUV39H1–HP1 interaction↓	Likely possible where the complex is present	P/R	Destabilization of heterochromatin organization	Covalent interaction of the ETP disulfide functionality with the SUV39H1 chromodomain provides a mechanism distinct from catalytic methyltransferase inhibition.
5	Mitochondrial apoptosis	MMP↓; cytochrome c↑; Bax↑; Bcl-2↓; caspase-9/3↑	Lower response reported in several comparison models	R/G	Intrinsic apoptosis↑	Strongly demonstrated in melanoma and supported in several additional tumor types. Mitochondria are an important execution pathway but are not required for all chaetocin-mediated cytotoxicity.
6	Death receptor / extrinsic apoptosis	DR5↑; caspase-8↑; apoptosis↑	↔ in some comparison models	R/G	Extrinsic apoptosis and apoptosis priming	ROS-dependent death-receptor transcription and DR5 stabilization contribute particularly in leukemia and glioblastoma models.
7	ATM / YAP1 / p73 stress signaling	ATM↑; YAP1↑; YAP1-p73 signaling↑	Not adequately characterized	R/G	DNA-damage-associated apoptosis	Demonstrated in glioma and linked mechanistically to chaetocin-induced ROS.
8	PI3K / AKT survival signaling	PI3K↓; AKT↓	Context-dependent	R/G	Prosurvival signaling↓	ROS-mediated suppression is well demonstrated in gastric cancer and contributes to apoptosis.
9	Hsp90 / client-protein stability	Hsp90 function↓; oncogenic client proteins↓	Potential Hsp90 effects	R/G	Proteostasis disruption	Chaetocin can bind Hsp90 and promote degradation of Hsp90 clients. This reinforces its multitarget classification.
10	Glycolysis / glucose metabolism	Glucose uptake↓; glycolysis↓; lactate↓; ATP↓	Not adequately characterized	R/G	Metabolic stress	ROS/JNK-dependent metabolic suppression is particularly documented in glioma cells.
11	NRF2 antioxidant response	NRF2↑ early; NRF2↓ later (time-dependent)	Not adequately characterized	R/G	Transient antioxidant adaptation followed by failure	Secondary mechanism. In melanoma models NRF2, SOD2 and catalase rise during early oxidative stress but subsequently decline with prolonged exposure.
12	Cell cycle regulation	G1 or G2/M arrest↑ (model-dependent)	Limited evidence	G	Proliferation↓	The arrest phenotype differs among tumor models, indicating that cell-cycle modulation is downstream/context-dependent rather than a single universal chaetocin target.
13	Cancer stemness / GATA3 / STAT3 networks	Stemness↓; STAT3↓ (context-dependent)	↔ in selected normal-cell comparisons	G	Self-renewal and tumor initiation↓	Documented in bladder cancer stem cells and supported by newer glioma and diffuse midline glioma studies.
14	Angiogenesis / endothelial proliferation	Tumor vascularization↓; VEGF/Notch1 signaling↓ (context-dependent)	Endothelial proliferation↓	G	Angiogenesis↓	This is therapeutically relevant but also demonstrates that chaetocin is not universally tumor-cell selective.
15	Chemosensitization / apoptosis sensitization	Sensitivity↑	Limited evidence	G	Combination efficacy↑	Preclinical synergy or sensitization has been reported with TRAIL, ONC201, HDAC inhibition, auranofin and several other anticancer interventions. This remains preclinical.
16	Clinical Translation Constraint	Potent preclinical activity	Normal-tissue therapeutic window uncertain	G	Translation currently limited	No established human PK, therapeutic exposure, clinical efficacy or approved indication. Reactive ETP disulfides and broad target engagement complicate claims of pharmacologic selectivity.

P: 0–30 min R: 30 min–3 hr G: >3 hr

ROS, Reactive Oxygen Species: Click to Expand ⟱

Source: HalifaxProj (inhibit)

Type:

Reactive oxygen species (ROS) are highly reactive molecules that contain oxygen and can lead to oxidative stress in cells. They play a dual role in cancer biology, acting as both promoters and suppressors of cancer.
ROS can cause oxidative damage to DNA, leading to mutations that may contribute to cancer initiation and progression. So normally you want to inhibit ROS to prevent cell mutations.
However excessive ROS can induce apoptosis (programmed cell death) in cancer cells, potentially limiting tumor growth. Chemotherapy typically raises ROS.
-mitochondria is the main source of reactive oxygen species (ROS) (and the ETC is heavily related)
ROS Homeostasis in Cancer Cells and Its Potential as a Therapeutic Target

"Reactive oxygen species (ROS) are two electron reduction products of oxygen, including superoxide anion, hydrogen peroxide, hydroxyl radical, lipid peroxides, protein peroxides and peroxides formed in nucleic acids 1. They are maintained in a dynamic balance by a series of reduction-oxidation (redox) reactions in biological systems and act as signaling molecules to drive cellular regulatory pathways."
"During different stages of cancer formation, abnormal ROS levels play paradoxical roles in cell growth and death 8. A physiological concentration of ROS that maintained in equilibrium is necessary for normal cell survival. Ectopic ROS accumulation promotes cell proliferation and consequently induces malignant transformation of normal cells by initiating pathological conversion of physiological signaling networks. Excessive ROS levels lead to cell death by damaging cellular components, including proteins, lipid bilayers, and chromosomes. Therefore, both scavenging abnormally elevated ROS to prevent early neoplasia and facilitating ROS production to specifically kill cancer cells are promising anticancer therapeutic strategies, in spite of their contradictoriness and complexity."
"ROS are the collection of derivatives of molecular oxygen that occur in biology, which can be categorized into two types, free radicals and non-radical species. The non-radical species are hydrogen peroxide (H 2O 2 ), organic hydroperoxides (ROOH), singlet molecular oxygen ( 1 O 2 ), electronically excited carbonyl, ozone (O3 ), hypochlorous acid (HOCl, and hypobromous acid HOBr). Free radical species are super-oxide anion radical (O 2•−), hydroxyl radical (•OH), peroxyl radical (ROO•) and alkoxyl radical (RO•) [130]. Any imbalance of ROS can lead to adverse effects. H2 O 2 and O 2 •− are the main redox signalling agents. The cellular concentration of H2 O 2 is about 10−8 M, which is almost a thousand times more than that of O2 •−".
"Radicals are molecules with an odd number of electrons in the outer shell [393,394]. A pair of radicals can be formed by breaking a chemical bond or electron transfer between two molecules."

Recent investigations have documented that polyphenols with good antioxidant activity may exhibit pro-oxidant activity in the presence of copper ions, which can induce apoptosis in various cancer cell lines but not in normal cells. "We have shown that such cell growth inhibition by polyphenols in cancer cells is reversed by copper-specific sequestering agent neocuproine to a significant extent whereas iron and zinc chelators are relatively ineffective, thus confirming the role of endogenous copper in the cytotoxic action of polyphenols against cancer cells. Therefore, this mechanism of mobilization of endogenous copper." > Ions could be one of the important mechanisms for the cytotoxic action of plant polyphenols against cancer cells and is possibly a common mechanism for all plant polyphenols. In fact, similar results obtained with four different polyphenolic compounds in this study, namely apigenin, luteolin, EGCG, and resveratrol, strengthen this idea.
Interestingly, the normal breast epithelial MCF10A cells have earlier been shown to possess no detectable copper as opposed to breast cancer cells [24], which may explain their resistance to polyphenols apigenin- and luteolin-induced growth inhibition as observed here (Fig. 1). We have earlier proposed [25] that this preferential cytotoxicity of plant polyphenols toward cancer cells is explained by the observation made several years earlier, which showed that copper levels in cancer cells are significantly elevated in various malignancies. Thus, because of higher intracellular copper levels in cancer cells, it may be predicted that the cytotoxic concentrations of polyphenols required would be lower in these cells as compared to normal cells."

Majority of ROS are produced as a by-product of oxidative phosphorylation, high levels of ROS are detected in almost all cancers.
-It is well established that during ER stress, cytosolic calcium released from the ER is taken up by the mitochondrion to stimulate ROS overgeneration and the release of cytochrome c, both of which lead to apoptosis.

Note: Products that may raise ROS can be found using this database, by:
Filtering on the target of ROS, and selecting the Effect Direction of ↑

Targets to raise ROS (to kill cancer cells):
• NADPH oxidases (NOX): NOX enzymes are involved in the production of ROS.
    -Targeting NOX enzymes can increase ROS levels and induce cancer cell death.
    -eNOX2 inhibition leads to a high NADH/NAD⁺ ratio which can lead to increased ROS
• Mitochondrial complex I: Inhibiting can increase ROS production
• P53: Activating p53 can increase ROS levels(by inducing the expression of pro-oxidant genes)
• Nrf2 inhibition: regulates the expression of antioxidant genes. Inhibiting Nrf2 can increase ROS levels
• Glutathione (GSH): an antioxidant. Depleting GSH can increase ROS levels
• Catalase: Catalase converts H2O2 into H2O+O. Inhibiting catalase can increase ROS levels
• SOD1: converts superoxide into hydrogen peroxide. Inhibiting SOD1 can increase ROS levels
• PI3K/AKT pathway: regulates cell survival and metabolism. Inhibiting can increase ROS levels
• HIF-1α inhibition: regulates genes involved in metabolism and angiogenesis. Inhibiting HIF-1α can increase ROS
• Glycolysis: Inhibiting glycolysis can increase ROS levels • Fatty acid oxidation: Cancer cells often rely on fatty acid oxidation for energy production.
-Inhibiting fatty acid oxidation can increase ROS levels
• ER stress: Endoplasmic reticulum (ER) stress can increase ROS levels
• Autophagy: process by which cells recycle damaged organelles and proteins.
-Inhibiting autophagy can increase ROS levels and induce cancer cell death.
• KEAP1/Nrf2 pathway: regulates the expression of antioxidant genes.
    -Inhibiting KEAP1 or activating Nrf2 can increase ROS levels and induce cancer cell death.
• DJ-1: regulates the expression of antioxidant genes. Inhibiting DJ-1 can increase ROS levels
• PARK2: regulates the expression of antioxidant genes. Inhibiting PARK2 can increase ROS levels
• SIRT1 inhibition:regulates the expression of antioxidant genes. Inhibiting SIRT1 can increase ROS levels
• AMPK activation: regulates energy metabolism and can increase ROS levels when activated.
• mTOR inhibition: regulates cell growth and metabolism. Inhibiting mTOR can increase ROS levels
• HSP90 inhibition: regulates protein folding and can increase ROS levels when inhibited.
• Proteasome: degrades damaged proteins. Inhibiting the proteasome can increase ROS levels
• Lipid peroxidation: a process by which lipids are oxidized, leading to the production of ROS.
    -Increasing lipid peroxidation can increase ROS levels
• Ferroptosis: form of cell death that is regulated by iron and lipid peroxidation.
    -Increasing ferroptosis can increase ROS levels
• Mitochondrial permeability transition pore (mPTP): regulates mitochondrial permeability.
    -Opening the mPTP can increase ROS levels
• BCL-2 family proteins: regulate apoptosis and can increase ROS levels when inhibited.
• Caspase-independent cell death: a form of cell death that is regulated by ROS.
    -Increasing caspase-independent cell death can increase ROS levels
• DNA damage response: regulates the repair of DNA damage. Increasing DNA damage can increase ROS
• Epigenetic regulation: process by which gene expression is regulated.
    -Increasing epigenetic regulation can increase ROS levels

-PKM2, but not PKM1, can be inhibited by direct oxidation of cysteine 358 as an adaptive response to increased intracellular reactive oxygen species (ROS)

ProOxidant Strategy:(inhibit the Mevalonate Pathway (likely will also inhibit GPx)
-HydroxyCitrate (HCA) found as supplement online and typically used in a dose of about 1.5g/day or more
-Atorvastatin typically 40-80mg/day, -Dipyridamole typically 200mg 2x/day Combined effect research
-Lycopene typically 100mg/day range (note debatable as it mainly lowers NRF2)

Dual Role of Reactive Oxygen Species and their Application in Cancer Therapy

ROS-Inducing Interventions in Cancer — Canonical + Mechanistic Reference
-generated from AI and Cancer database
ROS rating:  +++ strong | ++ moderate | + weak | ± mixed | 0 none
NRF2:        ↓ suppressed | ↑ activated | ± mixed | 0 none
Conditions:  [D] dose  [Fe] metal  [M] metabolic  [O₂] oxygen
             [L] light [F] formulation [T] tumor-type [C] combination


Item  ROS↑  NRF2  Condition  Mechanism Class  Remarks  

ROS">Piperlongumine
+++  ↓  [D][T]  ROS-dominant
Selective <span class="wphighlight">ROS</span> stressor, Prevents compensatory upregulation of NRF2, ie GSH↓



ROS">Shikonin
+++ ↓/± [D][T] ROS-dominant
<span class="wphighlight">ROS</span> + glycolysis + GPX4 inhibition



ROS">Vitamin K3 (menadione)
+++ ↓ [D] ROS-dominant
Quinone redox cycler; toxicity limits use



ROS">Copper (ionic / nano)
+++ ↓ [Fe][F] ROS-dominant
Fenton-type redox chemistry



ROS">Sodium Selenite
+++ ↓ [D] ROS-dominant
Pro-oxidant, depletes GSH



ROS">Juglone
+++ ↓ [D] ROS-dominant
Strong quinone <span class="wphighlight">ROS</span> chemistry



ROS">Auranofin
+++ ↓ [D] ROS-dominant
TrxR inhibition → redox collapse



ROS">Photodynamic Therapy (PDT)
+++ 0 [L][O₂] ROS-dominant
Singlet oxygen is core cytotoxic mechanism



ROS">Radiotherapy / Radiation
+++ 0 [O₂] ROS-dominant
DNA damage largely via <span class="wphighlight">ROS</span>



ROS">Doxorubicin
+++ ↓ [D] ROS-dominant
Chemo; redox cycling + mitochondrial <span class="wphighlight">ROS</span>



ROS">Cisplatin
++ ↓ [D][T] ROS-dominant
<span class="wphighlight">ROS</span> contributes to DNA/protein damage



ROS">Salinomycin
++ ↓ [D][T] ROS-dominant
<span class="wphighlight">ROS</span>-mediated CSC toxicity



ROS">Artemisinin / DHA
++ ↓ [Fe][T] ROS-dominant
Iron-activated radical generation



ROS">Sulfasalazine
++ ↓ [C][T] ROS-dominant
Ferroptosis; xCT inhibition → lipid <span class="wphighlight">ROS</span>



ROS">FMD / fasting
++ ↓ [M][C][O₂] ROS-dominant
Metabolic stress → mitochondrial <span class="wphighlight">ROS</span>



ROS">Vitamin C (pharmacologic)
++ ↓ [Fe][D] ROS-dominant
Extracellular H₂O₂ at high dose



ROS">Silver nanoparticles
++ ± [F][D] ROS-dominant
<span class="wphighlight">ROS</span> common; selectivity unreliable



ROS">Gambogic acid
++ ↓ [D][T] ROS-dominant
<span class="wphighlight">ROS</span>-mediated apoptosis



ROS">Parthenolide
++ ↓ [D][T] ROS-dominant
<span class="wphighlight">ROS</span> + NF-κB suppression



ROS">Plumbagin
++ ↓ [D] ROS-dominant
Quinone <span class="wphighlight">ROS</span> driver



ROS">Allicin
++ ↓ [D] ROS-dominant
Thiol-reactive oxidative stress



ROS">Ashwagandha (Withaferin A)
++ ↓ [D][T] ROS-dominant
<span class="wphighlight">ROS</span>-mediated apoptosis



ROS">Berberine
++ ↓ [D][M] ROS-dominant
Mitochondrial <span class="wphighlight">ROS</span> induction



ROS">PEITC
++ ↓ [D][C] ROS-dominant
GSH depletion + <span class="wphighlight">ROS</span>



ROS">Methionine restriction
+ ↓ [M][C][T] ROS-secondary
Redox vulnerability increased; <span class="wphighlight">ROS</span> indirect



ROS">DCA
+ ± [M][T] ROS-secondary
<span class="wphighlight">ROS</span> via forced OXPHOS



ROS">Capsaicin
+ ± [D][T] ROS-secondary
Ca²⁺ stress → <span class="wphighlight">ROS</span>



ROS">Galloflavin
+ 0 [D] ROS-secondary
<span class="wphighlight">ROS</span> not primary driver



ROS">Piperine
+ ± [D][F] ROS-secondary
Weak <span class="wphighlight">ROS</span> induction



ROS">Propyl gallate
+ ↓ [D] ROS-secondary
Pro-oxidant at high dose



ROS">Scoulerine
+ ? [D][T] ROS-secondary
Sparse <span class="wphighlight">ROS</span> data



ROS">Thymoquinone
± ± [D][T] Dual redox
Antioxidant ↔ pro-oxidant switch



ROS">Emodin
± ± [D][T] Dual redox
Not cancer-exclusive



ROS">Alpha-lipoic acid (ALA)
± ↑ [D][M] NRF2-dominant
Antioxidant at low dose



ROS">Curcumin
± ↑/↓ [D][F] NRF2-dominant
Hormetic redox behavior



ROS">EGCG
± ↑/↓ [D][O₂] NRF2-dominant
Auto-oxidation artifacts common



ROS">Quercetin
± ↑/↓ [D][Fe] NRF2-dominant
GSH-dependent cycling



ROS">Resveratrol
± ↑ [D][M] NRF2-dominant
<span class="wphighlight">ROS</span> only at high dose



ROS">Sulforaphane
± ↑↑ [D] NRF2-dominant
Strong NRF2 activator



ROS">Lycopene
0 ↑ — Antioxidant
Consistently antioxidant



ROS">Rosmarinic acid
0 ↑ — Antioxidant
Primarily antioxidant



ROS">Citrate
0 0 — Neutral
Metabolic; not a <span class="wphighlight">ROS</span> agent

Scientific Papers found: Click to Expand⟱

7173-

CHA,

Natural compound chaetocin induced DNA damage and apoptosis through reactive oxygen species-dependent pathways in A549 lung cancer cells and in vitro evaluations

in-vitro,

Lung,

A549

54.3 ± 1.5 nM

TumCG↓, TumCCA↑, ROS↑, DNAdam↑, CD47↓, *toxicity↓, MMP↓, Casp3↑, mtDam↓,

7185-

CHA,

Chaetocin-induced ROS-mediated apoptosis involves ATM–YAP1 axis and JNK-dependent inhibition of glucose metabolism

vitro+vivo,

GBM,

A172

xenograft glioma mouse model

in-vitro,

GBM,

T98G

in-vitro,

GBM,

U87MG

HMTs↓, ROS↑, p‑ATM↑, YAP/TEAD↑, p‑JNK↑, TumPF↓, SUV39H↓, TrxR↓, Casp3↑, Trx1↓, H3↓, lactateProd↓, ATP↓, GlucoseCon↓, TumCG↓, Dose↝,

7184-

CHA,

Chaetocin antileukemia activity against chronic myelogenous leukemia cells is potentiated by bone marrow stromal factors and overcomes innate imatinib resistance

in-vitro,

CML,

ROS↑, TrxR↓, eff↓, eff↑,

7181-

CHA,

Chaetocin induces cell cycle arrest and apoptosis by regulating the ROS-mediated ASK-1/JNK signaling pathways

TumCCA↑, ROS↑, ASK1↑, JNK↑, HMTs↓, Trx↓, tumCV↓, TumCI↓,

7180-

CHA,

Chaetocin: A review of its anticancer potentials and mechanisms

Review,

Var,

TumCG↓, TumCP↓, Apoptosis↑, TumCCA↑, angioG↓, TumCI↓, TumCMig↓, SUV39H↓, TrxR↓, Hif1a↓, HSP90↓, ox-Trx1↑, ROS↑, PI3K↓, Akt↓, Casp3↑, Casp8↑, Casp9↑, cl‑PARP↑, Bcl-2↓, Bcl-xL↓, Mcl-1↓, XIAP↓, DR5↑, CHOP/DDIT3↑, ATF3↑, angioG↓, VEGF↑, LDHA↓, ENO1↓,

7176-

CHA,

Chaetocin enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis by enhancing DR5 stabilization and reactive oxygen species generation in human glioblastoma cells

in-vitro,

GBM,

U343

in-vitro,

GBM,

U87MG

in-vitro,

GBM,

U251

in-vitro,

GBM,

T98G

in-vitro,

Nor,

HEK293

Apoptosis↑, selectivity↑, ROS↑, DR5↑,

7159-

CHA,

ROS-mediated inactivation of the PI3K/AKT pathway is involved in the antigastric cancer effects of thioredoxin reductase-1 inhibitor chaetocin

vitro+vivo,

GC,

HGC27

in-vitro,

GC,

AGS

in-vitro,

GC,

BGC-823

in-vitro,

GC,

SGC-7901

in-vitro,

Nor,

HEK293

TumCP↓, TumCCA↑, Casp↑, Apoptosis↑, TrxR1↓, ROS↑, eff↓, eff↑, PI3K↓, Akt↓, TumCG↓, cl‑PARP↑, cl‑Casp3↑, cl‑Casp9↑, cl‑Casp8↑, Bcl-2↓, Bcl-xL↓, Mcl-1↓, XIAP↓, survivin↓, TumVol↓, TumW↓, Weight∅, toxicity↓, Ki-67↓, other↝,

7172-

CHA,

Chaetocin enhances tumor necrosis factor‑related apoptosis‑inducing ligand‑mediated apoptosis by enhancing DR5 stabilization and reactive oxygen species generation in human glioblastoma cells

NA,

GBM,

U343

NA,

GBM,

U87MG

NA,

GBM,

U251

NA,

GBM,

T98G

NA,

Nor,

HEK293

Casp↑, Apoptosis↑, selectivity↑, DR5↑, ROS↑,

7168-

CHA,

The anticancer effect of chaetocin is enhanced by inhibition of autophagy

vitro+vivo,

Liver,

HepG2

545.254nM

in-vitro,

Liver,

HepG3

253.388nM

in-vitro,

Liver,

HUH7

677.046 nM

Apoptosis↓, TumAuto↑, ROS↑, Hif1a↓, SUV39H↓, cl‑PARP↑, eff↑, eff↑,

7167-

CHA,

Chaetocin-induced ROS-mediated apoptosis involves ATM-YAP1 axis and JNK-dependent inhibition of glucose metabolism

vitro+vivo,

GBM,

A172

heterotypic xenograft glioma mouse model

in-vitro,

GBM,

T98G

in-vitro,

GBM,

U87MG

HMTs↓, ROS↑, YAP/TEAD↑, ATM↑, JNK↑, Apoptosis↑, GlucoseCon↓, lactateProd↓, ATP↓, TumCP↓, TrxR↓, Trx1↓, H3K9↓, p‑ATM↑, γH2AX↑, ALDOB↑, ENO3↑, FBP1↑, GSK‐3β↑, HK3↑, PCK1↑, PGK2↑, PGM1↑, PGM3↑, PHKG1↑, PKLR↑, HK2↓, PCNA↓,

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↓, Apoptosis↑, ROS↑, TumCCA↑, tumCV↓, Casp3↑, Casp9↑, Fas↑, FasL↑, DR4↑, P21↑, eff↓, eff↑,

7165-

CHA,

The anticancer agent chaetocin is a competitive substrate and inhibitor of thioredoxin reductase

in-vitro,

Cerv,

HeLa

ROS↑, TumCD↑, TrxR1↓, other↝, GSR↓, Trx↓, eff↓,

7164-

CHA,

Chaetocin induces apoptosis in human melanoma cells through the generation of reactive oxygen species and the intrinsic mitochondrial pathway, and exerts its anti-tumor activity in vivo

vitro+vivo,

Melanoma,

A375

12.55± 2.31 μM(A375)

TumCP↓, Apoptosis↑, ROS↑, eff↓, MMP↓, Cyt‑c↑, BAX↑, cl‑Casp3↑, cl‑Casp9↑, Bcl-2↓, TumCG↓, PCNA↓, tumCV↓, NRF2↑, SOD2↑, Catalase↑, NRF2↓, SOD2↓, Catalase↓, TrxR↓,

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

mice

ROS↑, Trx↓, Apoptosis↑, TumCG↓, SUV39H↓, Hif1a↓, TumCP↓, eff↓, MMP↓, TumCG↓, Dose↝, toxicity↓,

7160-

CHA,

Chaetocin: a promising new antimyeloma agent with in vitro and in vivo activity mediated via imposition of oxidative stress

in-vitro,

Lung,

A549

selectivity↑, eff↑, ROS↑, Apoptosis↓, HDAC↓, MMP↓, cl‑PARP↑, eff↑, eff↓, i-GSH∅,

Showing Research Papers: 1 to 15 of 15

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 15

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Functional Outcomes(tgid=23) ⓘ

toxicity↓, 1,
Total Targets: 1

Scientific Paper Hit Count for: ROS, Reactive Oxygen Species

15 chaetocin

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#:433  Target#:275  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

chaetocin / ROS Cancer Research Results

Chaetocin Mechanistic Profile

Pathway results for Effect on Cancer / Diseased Cells:

NA, unassigned(tgid=0) ⓘ

Redox & Oxidative Stress(tgid=1) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

Autophagy & Lysosomes(tgid=9) ⓘ

DNA Damage & Repair(tgid=10) ⓘ

Cell Cycle & Senescence(tgid=11) ⓘ

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

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Pathway results for Effect on Normal Cells:

Functional Outcomes(tgid=23) ⓘ

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