Celastrol / Prx 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)
Prx, Peroxiredoxin: Click to Expand ⟱
Source:
Type:
also known as Prx
Peroxiredoxins are endogenous antioxidants and redox sensors. Properties of the peroxiredoxins make them suitable as markers of oxidative stress.
Peroxiredoxins (Prxs) are a family of antioxidant enzymes that play a crucial role in cellular redox signaling and the detoxification of reactive oxygen species (ROS). They are involved in various cellular processes, including cell proliferation, differentiation, and apoptosis.
Prx isoforms (such as Prx1 and Prx4) are often overexpressed. This overexpression can help cancer cells cope with increased levels of reactive oxygen species (ROS) generated during rapid cell division and metabolic changes.
Elevated Prx levels have been linked to resistance against chemotherapy and radiation therapy. For example, Prx2 and Prx3 have been implicated in protecting cancer cells from oxidative damage caused by these treatments.
Some Prxs, such as Prx3, can act as tumor suppressors. Their downregulation or loss of function has been associated with increased tumorigenesis and poor prognosis in certain cancers.

PRDX family comprises several isoforms (for example, PRDX1, PRDX2, PRDX3, etc.) that function as antioxidant enzymes to reduce reactive oxygen species (ROS) and maintain redox balance.

PRDX family—especially key isoforms like PRDX1 and PRDX2—are often upregulated in various cancers, correlating with worse prognosis and enhanced tumor cell survival. Through their ROS-detoxifying capabilities, these proteins generally play protumorigenic roles by protecting malignant cells from oxidative stress and supporting resistance to apoptosis and therapy.


Scientific Papers found: Click to Expand⟱
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↓,
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↓,

Showing Research Papers: 1 to 2 of 2

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Catalase↑, 1,   HO-1↑, 1,   Prx↓, 2,   PrxII↓, 1,   ROS↑, 2,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,   mtDam↑, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,  

Cell Death ⓘ

Akt↑, 1,   Apoptosis↑, 1,   BAX↑, 1,   Casp3↑, 1,   Casp9↑, 1,   Cyt‑c↑, 1,   JNK↑, 1,  

Kinase & Signal Transduction ⓘ

Sp1/3/4↓, 1,  

Transcription & Epigenetics ⓘ

other↓, 1,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   ER Stress↑, 2,   HSP90↓, 2,  

Autophagy & Lysosomes ⓘ

TumAuto↑, 2,  

DNA Damage & Repair ⓘ

P53↑, 1,   cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

STAT3↓, 1,  

Migration ⓘ

MMP9↓, 1,   TumCI↓, 1,   TumCP↓, 1,   TumMeta↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   Hif1a↑, 1,  

Immune & Inflammatory Signaling ⓘ

CXCR4↓, 1,   IL6↓, 1,   Imm↝, 1,   Inflam↓, 1,   NF-kB↓, 1,   TNF-α↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 1,   eff↑, 2,  

Clinical Biomarkers ⓘ

IL6↓, 1,  

Functional Outcomes ⓘ

CardioT↑, 1,   chemoPv↑, 1,   hepatoP↓, 1,   neuroP↑, 1,   toxicity↑, 1,  
Total Targets: 45

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: Prx, Peroxiredoxin
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#:317  Target#:263  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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