Celastrol Cancer Research Results

Cela, Celastrol: Click to Expand ⟱
Features:

Celastrol — a quinone methide pentacyclic triterpenoid natural product isolated mainly from Tripterygium wilfordii and related Celastraceae plants. It is best classified as a pleiotropic redox-reactive small molecule with proteostasis-disrupting, anti-inflammatory, and anticancer activity. Standard abbreviations include Cel and CeT. In oncology, celastrol is best viewed as a preclinical multi-target stress inducer rather than a selective single-node inhibitor, with recurring emphasis on thiol-reactive proteostasis disruption, NF-κB suppression, ROS-linked mitochondrial injury, and context-dependent inhibition of STAT3 and PI3K/AKT signaling. Clinically important caveats are poor water solubility, poor oral bioavailability, rapid disposition, and a narrow therapeutic window that has driven strong interest in nanoformulations and conjugates.

Primary mechanisms (ranked):

  1. Proteostasis disruption with functional HSP90 inhibition and heat-shock response activation
  2. NF-κB pathway suppression through inhibition of pro-survival inflammatory signaling
  3. ROS elevation with mitochondrial dysfunction and intrinsic apoptosis
  4. JAK2/STAT3 axis inhibition in responsive tumor contexts
  5. Secondary down-modulation of PI3K/AKT/mTOR and related growth-survival signaling
  6. Context-dependent suppression of invasion, angiogenesis, and metastatic programs including CXCR4 and HIF-1-related outputs
  7. Chemosensitization and stress-vulnerability amplification in selected resistant tumor models

Bioavailability / PK relevance: Celastrol is practically insoluble or very poorly soluble in water, has poor oral bioavailability, and shows dose-limiting systemic toxicity; delivery systems are commonly used to improve exposure and reduce off-target injury.

In-vitro vs systemic exposure relevance: Many mechanistic and cytotoxicity studies use low-micromolar concentrations that are difficult to reproduce safely with conventional systemic dosing. Some pathway effects may still occur at lower exposures, but direct tumoricidal effects are often concentration-limited without advanced formulations.

Clinical evidence status: Strong preclinical oncology signal; early translational and formulation work; no approved cancer indication. Human clinical registration appears limited to non-oncology safety/other exploratory studies rather than established anticancer efficacy trials. *** Appears more useful used at lower doses in combined treatment approaches.

Celastrol—a bioactive compound extracted from traditional Chinese medicinal plants such as Tripterygium wilfordii (Thunder God Vine).

Pathways:
-inhibit NF-κB activation
-disrupt the function of chaperone proteins like HSP90 and HSP70, which are often overexpressed in cancer cells
-attenuate Akt phosphorylation and downstream mTOR signaling
-modulate components of the MAPK pathway, including ERK, JNK, and p38.
-increase intracellular ROS levels in cancer cells
-inhibiting STAT3

Celastrol mechanistic map in cancer

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 HSP90 proteostasis disruption ↓ client protein stability; ↑ heat-shock stress ↑ stress response (dose-dependent) P/R Destabilization of oncogenic signaling networks Mechanistically central and industry-relevant. Celastrol behaves as a thiol-reactive disruptor of chaperone-dependent proteostasis rather than a highly selective kinase inhibitor.
2 NF-κB inflammatory survival signaling ↓ ↓ inflammatory tone R/G Reduced survival, proliferation, cytokine signaling, and invasion One of the most reproducible anticancer themes; also helps explain anti-inflammatory overlap outside oncology.
3 Mitochondrial ROS increase ↑ (primary; dose-dependent) ↑ (high concentration only) P/R Oxidative stress overload and stress sensitization The quinone methide scaffold is redox-reactive. ROS often acts upstream of mitochondrial depolarization, apoptosis, and therapy sensitization.
4 Mitochondria and intrinsic apoptosis MMP ↓; Bax/Bcl-2 balance toward apoptosis; caspases ↑ ↑ injury at higher exposure R/G Apoptotic tumor cell death Usually linked to ROS and proteotoxic stress rather than an isolated primary target.
5 JAK2 STAT3 signaling ↓ (context-dependent) ↔ R/G Reduced proliferation, survival, and inflammatory transcription Supported in multiple tumor models, including myeloma and more recent metastatic-cancer work, but not necessarily dominant in every model.
6 PI3K AKT mTOR axis ↓ (secondary) ↔ / ↓ R/G Anabolic and survival suppression Often appears downstream of broader stress and chaperone disruption.
7 Invasion metastasis and angiogenesis programs CXCR4 ↓; motility ↓; VEGF signaling ↓; HIF-1α ↔ (context-dependent) ↔ G Reduced metastatic competence and tumor vascular support HIF-1-related effects are mixed across sources and models; anti-invasive and anti-angiogenic effects are better supported than a uniform HIF-1α direction.
8 NRF2 antioxidant response ↑ adaptive defense or overwhelm (context-dependent) ↑ cytoprotective stress response R/G Bidirectional redox adaptation Relevant, but not a clean core anticancer mechanism. NRF2 activation can be protective in normal tissue yet may also buffer tumor oxidative stress in some settings.
9 Chemosensitization ↑ therapy response ↔ / toxicity risk G Overcoming resistance in selected models Supported especially where NF-κB/STAT3-dependent resistance is prominent; still largely preclinical.
10 Clinical Translation Constraint Exposure limited Toxicity limited — Narrow therapeutic window Poor solubility, poor oral bioavailability, rapid metabolism/disposition, and organ-toxicity risk are major barriers to systemic oncology use.

TSF legend:
P: 0–30 min (direct redox/protein interactions)
R: 30 min–3 hr (acute stress and signaling shifts)
G: >3 hr (gene regulation and phenotype outcomes)
Scientific Papers found: Click to Expand⟱
5944- Cela,    HSP90 inhibitor, celastrol, arrests human monocytic leukemia cell U937 at G0/G1 in thiol-containing agents reversible way
- in-vitro, AML, U937
TumCP↓, TumCCA↑, TumCD↑, HSP90↓, HSP70/HSPA5↑, cycD1/CCND1↓, CDK4↓, CDK6↓, ATPase↓,
5953- Cela,  CUR,    The Combination of Celastrol and Curcumin Enhances the Antitumor Effect in Nasopharyngeal Carcinoma by Inducing Ferroptosis
- vitro+vivo, NPC, NA
eff↑, TumCP↓, GPx4↓, eff↑, TumAuto↑, Ferroptosis↑, Dose↝, ACSL4↑, toxicity↓,
5952- Cela,    Celastrol attenuates Alzheimer’s disease-mediated learning and memory impairment by inhibiting endoplasmic reticulum stress-induced inflammation and oxidative stress
- in-vivo, AD, NA
*memory↑, *Inflam↓, *ROS↓, *ER Stress↓, *neuroP↑, *Dose↝, *MDA↓, *SOD↑, *Catalase↑, *Aβ↓, BACE↓, LRP1↑, RAGE↓,
5951- Cela,    Celastrol Suppresses Tumor Cell Growth through Targeting an AR-ERG-NF-κB Pathway in TMPRSS2/ERG Fusion Gene Expressing Prostate Cancer
- vitro+vivo, Pca, NA
NF-kB↓, AR↓, MCP1↓, Akt↓, HSP90↓, TumCG↓,
5950- Cela,    Anticancer Inhibitors of Hsp90 Function: Beyond the Usual Suspects
- Review, Var, NA
ChemoSen↑, HSP90↓, Akt↓, CDK4↓,
5949- Cela,    Celastrol suppresses invasion of colon and pancreatic cancer cells through the downregulation of expression of CXCR4 chemokine receptor
- in-vitro, BC, MCF-7
CXCR4↓, eff↑, TumCI↓, TumMeta↓,
5948- Cela,    Recent Trends in anti-tumor mechanisms and molecular targets of celastrol
TumCP↓, TumCCA↑, Apoptosis↑, TumAuto↑, TumCI↓, TumMeta↓, Imm↝, angioG↓, Cyt‑c↑, ROS↑, BAX↑, Casp3↑, Casp9↑, cl‑PARP↑, PrxII↓, ER Stress↑, mtDam↑, CHOP↑, Inflam↓, NF-kB↓, CXCR4↓, MMP9↓, IL6↓, TNF-α↓, HSP90↓, neuroP↑, STAT3↓, Prx↓, HO-1↑, eff↑, eff↑, BioAv↑, toxicity↑, CardioT↑, hepatoP↓,
5947- Cela,    Recent advances in drug delivery of celastrol for enhancing efficiency and reducing the toxicity
- Review, Var, NA
BioAv↓, toxicity⇅, BioAv↑,
5946- Cela,    The anti-cancer mechanism of Celastrol by targeting JAK2/STAT3 signaling pathway in gastric and ovarian cancer
- in-vitro, Var, NA
toxicity⇅, toxicity↓, TumCG↓, ROS↑, IL6↓, JAK2↓, STAT3↓,
5945- Cela,    Targeting the dynamic HSP90 complex in cancer
- Review, Var, NA
HSP90↓,
2392- Cela,    The role of natural products targeting macrophage polarization in sepsis-induced lung injury
- Review, Sepsis, NA
TNF-α↓, IL1β↓, IL6↓, Warburg↓, PKM2↓, NRF2↑, HO-1↑, NF-kB↓, iNOS↓, M1↓,
5943- Cela,    Celastrol: A Spectrum of Treatment Opportunities in Chronic Diseases
- Review, Arthritis, NA - Review, IBD, NA - Review, AD, NA - Review, Park, NA
*other↝, *other↝, *CRP↓, *eff↝, *other↑, *CXCR4↓, *IL1β↓, *IL6↓, *IL17↓, *IL18↓, *TNF-α↓, *MMP9↓, *PGE2↓, *COX1↓, *COX2↓, *PI3K↓, *Akt↓, *other↑, TumCCA↑, Apoptosis↑, ROS↑, JNK↑, TumAuto↑, Hif1a↓, BNIP3↝, HSP90↓, Fas↑, FasL↑, ETC↓, VEGF↓, angioG↓, RadioS↑, *neuroP↑, *HSP70/HSPA5↑, *ROS↓, *MMP↑, *Cyt‑c↓, *Casp3↓, *Casp9↓, *MAPK↓, *Dose⇅, *HSPs↑, BioAv↓, Dose↝,
5942- Cela,    Celastrol elicits antitumor effects by inhibiting the STAT3 pathway through ROS accumulation in non-small cell lung cancer
- vitro+vivo, NSCLC, H460 - in-vitro, NSCLC, PC9
TumCG↓, TumCP↓, TumMeta↓, ROS↑, ER Stress↑, p‑STAT3↓, Apoptosis↑, eff↓, TumCG↓, IL6↓, other↝,
5941- Cela,    Celastrol inhibits migration and invasion through blocking the NF-κB pathway in ovarian cancer cells
- in-vitro, Ovarian, SKOV3 - in-vitro, Ovarian, OVCAR-3
TumCMig↓, TumCI↓, NF-kB↓, p65↓, MMP9↓, eff↑, AntiTum↑, Inflam↓, AntiDiabetic↑,
5940- Cela,    Celastrol Suppresses Angiogenesis-Mediated Tumor Growth through Inhibition of AKT/Mammalian Target of Rapamycin Pathway
- in-vivo, Pca, PC3
Dose↝, TumVol↓, TumW↓, angioG↓, VEGF↓, TumCMig↓, TumCP↓, TumCI↓, Akt↓, mTOR↓, P70S6K↓,
5939- Cela,  Chemo,    Celastrol inhibits proliferation and induces chemosensitization through down-regulation of NF-κB and STAT3 regulated gene products in multiple myeloma cells
- in-vitro, Melanoma, U266 - in-vitro, Melanoma, RPMI-8226
TumCP↓, ChemoSen↑, cycD1/CCND1↓, Bcl-2↓, survivin↓, XIAP↓, Mcl-1↓, NF-kB↓, IL6↓, STAT3↓, Apoptosis↑, TumCCA↑, Casp3↑, HSP90↓, HO-1↑, JAK2↓, Src↓, Akt↑,
5938- Cela,    Celastrol: A Review of Useful Strategies Overcoming its Limitation in Anticancer Application
- Review, Var, NA
AntiCan↑, BioAv↓, Apoptosis↑, TumAuto↑, TumCCA↑, TumMeta↓, angioG↓, Inflam↓, antiOx↑, ChemoSen↑, HSP90↓, ROS↑, RadioS↑, P53↑, NLRP3↓,
2653- Cela,    Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical Evidence
- Review, Var, NA
chemoPv↑, Catalase↑, ROS↑, HSP90↓, Sp1/3/4↓, AMPK↑, P53↑, JNK↑, ER Stress↑, MMP↓, TumCCA↑, TumAuto↑, Hif1a↑, Akt↑, other↓, Prx↓,
2393- Cela,    Celastrol mitigates inflammation in sepsis by inhibiting the PKM2-dependent Warburg effect
- in-vivo, Sepsis, NA - in-vitro, Nor, RAW264.7
OS↑, PKM2↓, Glycolysis↓, Warburg↓, Inflam↓, HMGB1↓, ALAT↓, AST↓, TNF-α↓, IL1β↓, IL6↓,

Showing Research Papers: 1 to 19 of 19

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 19

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   Catalase↑, 1,   Ferroptosis↑, 1,   GPx4↓, 1,   HO-1↑, 3,   NRF2↑, 1,   Prx↓, 2,   PrxII↓, 1,   ROS↑, 6,  

Mitochondria & Bioenergetics ⓘ

ETC↓, 1,   MMP↓, 1,   mtDam↑, 1,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

ACSL4↑, 1,   ALAT↓, 1,   AMPK↑, 1,   Glycolysis↓, 1,   PKM2↓, 2,   Warburg↓, 2,  

Cell Death ⓘ

Akt↓, 3,   Akt↑, 2,   Apoptosis↑, 5,   BAX↑, 1,   Bcl-2↓, 1,   Casp3↑, 2,   Casp9↑, 1,   Cyt‑c↑, 1,   Fas↑, 1,   FasL↑, 1,   Ferroptosis↑, 1,   iNOS↓, 1,   JNK↑, 2,   Mcl-1↓, 1,   survivin↓, 1,   TumCD↑, 1,  

Kinase & Signal Transduction ⓘ

Sp1/3/4↓, 1,  

Transcription & Epigenetics ⓘ

other↓, 1,   other↝, 1,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   ER Stress↑, 3,   HSP70/HSPA5↑, 1,   HSP90↓, 9,  

Autophagy & Lysosomes ⓘ

BNIP3↝, 1,   TumAuto↑, 5,  

DNA Damage & Repair ⓘ

P53↑, 2,   cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

CDK4↓, 2,   cycD1/CCND1↓, 2,   TumCCA↑, 6,  

Proliferation, Differentiation & Cell State ⓘ

mTOR↓, 1,   P70S6K↓, 1,   Src↓, 1,   STAT3↓, 3,   p‑STAT3↓, 1,   TumCG↓, 4,  

Migration ⓘ

ATPase↓, 1,   LRP1↑, 1,   MMP9↓, 2,   RAGE↓, 1,   TumCI↓, 4,   TumCMig↓, 2,   TumCP↓, 6,   TumMeta↓, 4,  

Angiogenesis & Vasculature ⓘ

angioG↓, 4,   Hif1a↓, 1,   Hif1a↑, 1,   VEGF↓, 2,  

Immune & Inflammatory Signaling ⓘ

CXCR4↓, 2,   HMGB1↓, 1,   IL1β↓, 2,   IL6↓, 6,   Imm↝, 1,   Inflam↓, 4,   JAK2↓, 2,   M1↓, 1,   MCP1↓, 1,   NF-kB↓, 5,   p65↓, 1,   TNF-α↓, 3,  

Protein Aggregation ⓘ

BACE↓, 1,   NLRP3↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,   CDK6↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 3,   BioAv↑, 2,   ChemoSen↑, 3,   Dose↝, 3,   eff↓, 1,   eff↑, 6,   RadioS↑, 2,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   AR↓, 1,   AST↓, 1,   IL6↓, 6,   RAGE↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   AntiDiabetic↑, 1,   AntiTum↑, 1,   CardioT↑, 1,   chemoPv↑, 1,   hepatoP↓, 1,   neuroP↑, 1,   OS↑, 1,   toxicity↓, 2,   toxicity↑, 1,   toxicity⇅, 2,   TumVol↓, 1,   TumW↓, 1,  
Total Targets: 108

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

Catalase↑, 1,   MDA↓, 1,   ROS↓, 2,   SOD↑, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↑, 1,  

Cell Death ⓘ

Akt↓, 1,   Casp3↓, 1,   Casp9↓, 1,   Cyt‑c↓, 1,   MAPK↓, 1,  

Transcription & Epigenetics ⓘ

other↑, 2,   other↝, 2,  

Protein Folding & ER Stress ⓘ

ER Stress↓, 1,   HSP70/HSPA5↑, 1,   HSPs↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

PI3K↓, 1,  

Migration ⓘ

MMP9↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX1↓, 1,   COX2↓, 1,   CRP↓, 1,   CXCR4↓, 1,   IL17↓, 1,   IL18↓, 1,   IL1β↓, 1,   IL6↓, 1,   Inflam↓, 1,   PGE2↓, 1,   TNF-α↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 1,  

Drug Metabolism & Resistance ⓘ

Dose⇅, 1,   Dose↝, 1,   eff↝, 1,  

Clinical Biomarkers ⓘ

CRP↓, 1,   IL6↓, 1,  

Functional Outcomes ⓘ

memory↑, 1,   neuroP↑, 2,  
Total Targets: 36

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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