Eurycomanone / Casp3 Cancer Research Results

EU, Eurycomanone: Click to Expand ⟱
Features:

Eurycomanone — Eurycomanone is a highly oxygenated quassinoid diterpenoid from Eurycoma longifolia Jack, commonly known as tongkat ali or longjack. It is a small-molecule plant secondary metabolite and should be classified as a natural-product quassinoid, not as an essential oil constituent. It is best indexed separately from crude Eurycoma longifolia extract because isolated eurycomanone has specific anticancer mechanisms, while commercial tongkat ali extracts have variable composition and separate androgenic/supplement safety issues.

Primary mechanisms (ranked):

  1. Induction of intrinsic apoptosis through p53 activation, ↑ Bax, ↓ Bcl-2, and downstream caspase activation.
  2. Suppression of cancer-cell proliferation, clonogenic growth, and cell-cycle progression in multiple in-vitro cancer models.
  3. Autophagy inhibition in colon cancer through mTOR activation, ↓ LC3-II, and reduced autophagosome formation.
  4. Anti-invasive and anti-EMT activity in NSCLC models through inhibition of TGF-β1-linked Smad and non-Smad signaling, including Akt-linked effects and ↓ MMP-2 secretion.
  5. Anti-angiogenic signaling in colon cancer models, mainly as a preclinical tumor-support pathway effect.
  6. Context-dependent modulation of steroidogenic pathways, including aromatase and phosphodiesterase inhibition; this is pharmacologically relevant but not a core anticancer mechanism.

Bioavailability / PK relevance: Oral exposure is plausible but constrained by formulation, extract matrix, and rapid disposition; pure eurycomanone and standardized Eurycoma extracts are not interchangeable for PK interpretation. Cancer evidence is mostly based on isolated compound exposure in cell culture, so achievable systemic concentrations remain a major translation constraint.

In-vitro vs systemic exposure relevance: Several anticancer studies use micromolar or microgram-per-mL concentrations that may exceed typical nutraceutical oral exposure. Non-toxic anti-invasive NSCLC work used sub-cytotoxic micromolar doses, but clinical relevance remains uncertain without cancer PK/PD data. This is concentration-driven pharmacology, not field-based or trigger-based therapy.

Clinical evidence status: Preclinical only for cancer. No cancer RCTs, no oncology deployment, and no regulatory approval as an anticancer drug. Human studies and supplement safety data relate mainly to Eurycoma longifolia extracts for male-health indications, not isolated eurycomanone for cancer.

Eurycomanone Mechanistic Profile

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 p53 Bax Bcl-2 mitochondrial apoptosis ↑ p53, ↑ Bax, ↓ Bcl-2, ↑ apoptosis Relative sparing reported in some non-malignant comparator cells, but not fully established G Intrinsic apoptotic killing Most central anticancer mechanism; reported in HepG2, cervical carcinoma, breast cancer, and leukemia-related models.
2 Caspase 9 caspase 3 apoptosis execution ↑ caspase-dependent apoptosis Model-dependent selectivity G Execution-phase apoptosis Fits mitochondrial apoptosis pattern; strongest when paired with p53 Bax Bcl-2 findings.
3 Proliferation and cell-cycle control ↓ proliferation, ↓ colony formation, cell-cycle arrest (model-dependent) Less defined G Growth suppression Broad preclinical anticancer signal, but potency and selectivity vary by cell line and assay.
4 mTOR autophagy inhibition ↑ mTOR signaling, ↓ LC3-II, ↓ GFP-LC3 puncta, ↓ protective autophagy Not well characterized R/G Reduced survival autophagy Colon cancer data suggest autophagy supports survival under eurycomanone stress; autophagy inhibition strengthens growth inhibition.
5 TGF-β1 EMT Smad signaling ↓ EMT, ↓ migration, ↓ invasion, ↑ E-cadherin or ↓ N-cadherin depending on cell line Not established G Anti-invasive effect Relevant to metastatic NSCLC behavior; effects differ between A549 and Calu-1 cells.
6 Akt non-Smad EMT signaling ↓ Akt-linked EMT signaling (context-dependent) Not established R/G Migration and invasion suppression Secondary to TGF-β1 anti-EMT mechanism; therapeutic leverage is anti-metastatic rather than direct cytotoxicity.
7 MMP-2 extracellular matrix invasion ↓ MMP-2 secretion, ↓ Matrigel invasion Not established G Reduced matrix invasion Supports anti-metastatic classification in NSCLC models.
8 Angiogenesis support signaling ↓ angiogenesis-associated activity in colon cancer models Normal endothelial-cell selectivity not fully defined G Reduced tumor-support signaling Preclinical pathway; not sufficient alone to classify as a validated anti-angiogenic therapy.
9 A549 tumor marker proteins ↓ prohibitin, ↓ annexin 1, ↓ ERp28 reported Not established G Proteomic tumor phenotype modulation Useful as supporting mechanistic evidence in lung cancer, but less central than apoptosis or EMT inhibition.
10 ROS NRF2 oxidative stress Insufficient direct eurycomanone cancer evidence for core ranking Eurycoma extract shows antioxidant effects in non-cancer models G Context-dependent stress modulation ROS or NRF2 is NOT a primary cancer mechanism.
11 Steroidogenesis aromatase phosphodiesterase Potential hormone-context relevance, not a direct anticancer axis ↑ androgenic or fertility-related signaling in reproductive models G Endocrine pharmacology Important safety and interpretation constraint, especially for hormone-sensitive disease contexts.
12 Clinical Translation Constraint In-vitro potency may not match oral systemic exposure Supplement safety is extract-dependent; liver injury is a possible rare concern G Limits clinical use Main constraints are oral PK, extract variability, lack of cancer trials, dose ceiling, possible hepatotoxicity signal, and uncertain normal-cell therapeutic window.

TSF legend: P: 0–30 min R: 30 min–3 hr G: >3 hr
Casp3, CPP32, Cysteinyl aspartate specific proteinase-3: Click to Expand ⟱
Source:
Type:
Also known as CP32.
Cysteinyl aspartate specific proteinase-3 (Caspase-3) is a common key protein in the apoptosis and pyroptosis pathways, and when activated, the expression level of tumor suppressor gene Gasdermin E (GSDME) determines the mechanism of tumor cell death.
As a key protein of apoptosis, caspase-3 can also cleave GSDME and induce pyroptosis. Loss of caspase activity is an important cause of tumor progression.
Many anticancer strategies rely on the promotion of apoptosis in cancer cells as a means to shrink tumors. Crucial for apoptotic function are executioner caspases, most notably caspase-3, that proteolyze a variety of proteins, inducing cell death. Paradoxically, overexpression of procaspase-3 (PC-3), the low-activity zymogen precursor to caspase-3, has been reported in a variety of cancer types. Until recently, this counterintuitive overexpression of a pro-apoptotic protein in cancer has been puzzling. Recent studies suggest subapoptotic caspase-3 activity may promote oncogenic transformation, a possible explanation for the enigmatic overexpression of PC-3. Herein, the overexpression of PC-3 in cancer and its mechanistic basis is reviewed; collectively, the data suggest the potential for exploitation of PC-3 overexpression with PC-3 activators as a targeted anticancer strategy.
Caspase 3 is the main effector caspase and has a key role in apoptosis. In many types of cancer, including breast, lung, and colon cancer, caspase-3 expression is reduced or absent.
On the other hand, some studies have shown that high levels of caspase-3 expression can be associated with a better prognosis in certain types of cancer, such as breast cancer. This suggests that caspase-3 may play a role in the elimination of cancer cells, and that therapies aimed at activating caspase-3 may be effective in treating certain types of cancer.
Procaspase-3 is a apoptotic marker protein.
Prognostic significance:
• High Cas3 expression: Associated with good prognosis and increased sensitivity to chemotherapy in breast, gastric, lung, and pancreatic cancers.
• Low Cas3 expression: Linked to poor prognosis and increased risk of recurrence in colorectal, hepatocellular carcinoma, ovarian, and prostate cancers.
Scientific Papers found: Click to Expand⟱
6583- EU,    Inactivation of AKT/NF-κB signaling by eurycomalactone decreases human NSCLC cell viability and improves the chemosensitivity to cisplatin
- in-vitro, NSCLC, A549 - in-vitro, NSCLC, Calu-1
tumCV↓, TumCCA↑, Casp3↑, PARP↑, Bcl-xL↓, survivin↓, Akt↓, NF-kB↓, ChemoSen↑,
6586- EU,    Unfermented Freeze-Dried Leaf Extract of Tongkat Ali (Eurycoma longifolia Jack.) Induced Cytotoxicity and Apoptosis in MDA-MB-231 and MCF-7 Breast Cancer Cell Lines
TumCD↑, DNAdam↑, TumCCA↑, Cyt‑c↑, Casp3↑,

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:


Cell Death ⓘ

Akt↓, 1,   Bcl-xL↓, 1,   Casp3↑, 2,   Cyt‑c↑, 1,   survivin↓, 1,   TumCD↑, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   PARP↑, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 2,  

Immune & Inflammatory Signaling ⓘ

NF-kB↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,  
Total Targets: 12

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: Casp3, CPP32, Cysteinyl aspartate specific proteinase-3
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#:415  Target#:42  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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