Nimbolide / TumCI Cancer Research Results

Nimb, Nimbolide: Click to Expand ⟱
Features:
Nimbolide is a compound found in the neem tree (Azadirachta indica) and has been studied for its potential anti-cancer properties. nimbolide is a neem-derived tetranortriterpenoid limonoid from Azadirachta indica.

Research has shown that nimbolide has anti-proliferative and pro-apoptotic effects on various types of cancer cells, including breast, lung, colon, and prostate cancer cells. It has also been shown to inhibit the growth of cancer cells by inducing cell cycle arrest and apoptosis (programmed cell death).

Some of the ways in which nimbolide may help to prevent or treat cancer include:
-Inhibiting the activity of certain enzymes that are involved in cancer cell growth and survival
-Inducing the production of reactive oxygen species (ROS) that can damage cancer cells
-Inhibiting the formation of new blood vessels that are needed to support the growth of cancer cells
-Enhancing the effectiveness of chemotherapy and radiation therapy

Nimbolide — Nimbolide is a neem-derived tetranortriterpenoid limonoid from Azadirachta indica with preclinical anticancer activity across multiple tumor models. It is best classified as a small-molecule plant limonoid / electrophilic triterpenoid natural product rather than as “neem oil” or whole neem extract. Standard abbreviation is NB or NL. aliases: “neem limonoids,” “neem extract,” and “Azadirachta indica limonoids”

Primary mechanisms (ranked):

  1. Covalent modulation of the ubiquitin-proteasome axis, especially RNF114-dependent substrate recognition and p21 stabilization.
  2. Mitochondrial oxidative stress induction through ROS elevation and SOD2 suppression in susceptible cancer cells.
  3. Apoptosis activation through caspase signaling, mitochondrial stress, and survival-pathway suppression.
  4. STAT3 and NF-κB pathway inhibition, reducing inflammatory survival signaling, proliferation, invasion, and anti-apoptotic transcription.
  5. EMT, migration, invasion, angiogenesis, and metastasis suppression in preclinical models.
  6. Autophagy modulation, including inhibition of cytoprotective autophagy in some tumor contexts.
  7. DNA damage response leverage, including RNF114-linked PARP1 trapping and reported synthetic-lethality relevance in BRCA-mutated models.

Bioavailability / PK relevance: Nimbolide is hydrophobic and poorly water-soluble, so systemic translation is constrained by formulation, solubility, exposure, metabolism, and tissue delivery. Nanoparticle and carrier-based formulations are being explored preclinically to improve delivery and anticancer exposure.

In-vitro vs systemic exposure relevance: Most anticancer findings use purified nimbolide in cell culture or animal models; direct equivalence to oral neem preparations is not established. Common in-vitro low-micromolar activity should not be assumed achievable with dietary or crude neem exposure. Whole neem oil or extract is chemically heterogeneous and may not deliver predictable nimbolide exposure.

Clinical evidence status: Preclinical. Evidence is strong enough for a database entry as a mechanistically interesting anticancer natural product, but not as a clinically validated anticancer therapy. No approved oncology indication or clear nimbolide-specific cancer trial status was identified; clinical use should be treated as unsupported outside research contexts.

Nimbolide Cancer Mechanism Table

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 RNF114 ubiquitin ligase axis RNF114 substrate recognition ↓; p21 stabilization ↑; proliferation ↓ Likely context-dependent; selectivity depends on dependency on RNF114-regulated substrates R/G Cell-cycle suppression and targeted-protein-degradation relevance High mechanistic importance because nimbolide has a defined electrophilic target interaction and can be used as a covalent recruiter scaffold.
2 Mitochondrial ROS and SOD2 ROS ↑; SOD2 ↓; mitochondrial stress ↑; apoptosis ↑ Potential oxidative-stress risk at sufficient exposure; selectivity is model-dependent R/G Oxidative apoptosis and metastasis suppression Core in pancreatic cancer models; may be especially relevant where tumor cells depend on antioxidant buffering.
3 Apoptosis and caspase activation Caspase 3 ↑; caspase 8 ↑; caspase 9 ↑; survival ↓ Lower effect reported in some normal-cell comparisons, but not universally established G Programmed cell death induction Central downstream phenotype across many cancer models.
4 STAT3 inflammatory survival signaling STAT3 phosphorylation ↓; anti-apoptotic transcription ↓; invasion ↓ Could suppress normal inflammatory or repair signaling if systemic exposure is high R/G Reduced proliferation, survival, and metastatic signaling Important in prostate and pancreatic cancer contexts; likely intersects with ROS and NF-κB effects.
5 NF-κB and Wnt beta catenin NF-κB activation ↓; IκB degradation ↓; Wnt beta catenin signaling ↓ Potential immune and epithelial-homeostasis effects are context-dependent R/G Anti-inflammatory, anti-survival, and anti-proliferative signaling Broadly reported in neem/nimbolide literature, but pathway dominance varies by tumor model.
6 Autophagy survival axis Cytoprotective autophagy ↓; apoptosis ↑ Autophagy effects may be protective or harmful depending on tissue stress state G Removal of tumor stress-adaptation capacity Secondary but therapeutically relevant where autophagy supports tumor survival.
7 EMT migration invasion metastasis EMT markers ↓; migration ↓; invasion ↓; metastatic traits ↓ Could affect normal wound-healing pathways at sufficient exposure G Anti-metastatic phenotype Strong preclinical relevance; not yet clinically validated.
8 Angiogenesis Pro-angiogenic signaling ↓ Physiologic angiogenesis may be affected in repair contexts G Reduced tumor vascular support Best treated as secondary/contextual unless a specific cancer model demonstrates angiogenesis as the dominant effect.
9 PARP1 trapping and BRCA synthetic lethality PARP1 trapping ↑; BRCA-mutated vulnerability ↑ DNA repair stress possible in proliferating normal cells R/G DNA-repair vulnerability exploitation Mechanistically interesting and industry-relevant, but narrower than the general ROS and ubiquitin-ligase mechanisms.
10 Clinical Translation Constraint In-vitro potency does not guarantee tumor exposure; formulation-dependent activity Safety margin uncertain for systemic use; crude neem products are not equivalent to purified nimbolide G Limits clinical interpretation Major constraints are poor solubility, uncertain human PK, lack of oncology trials, botanical heterogeneity, and neem toxicity concerns.

P: 0–30 min R: 30 min–3 hr G: >3 hr
TumCI, Tumor Cell invasion: Click to Expand ⟱
Source:
Type:
Tumor cell invasion is a critical process in cancer progression and metastasis, where cancer cells spread from the primary tumor to surrounding tissues and distant organs. This process involves several key steps and mechanisms:

1.Epithelial-Mesenchymal Transition (EMT): Many tumors originate from epithelial cells, which are typically organized in layers. During EMT, these cells lose their epithelial characteristics (such as cell-cell adhesion) and gain mesenchymal traits (such as increased motility). This transition is crucial for invasion.

2.Degradation of Extracellular Matrix (ECM): Tumor cells secrete enzymes, such as matrix metalloproteinases (MMPs), that degrade the ECM, allowing cancer cells to invade surrounding tissues. This degradation facilitates the movement of cancer cells through the tissue.

3.Cell Migration: Once the ECM is degraded, cancer cells can migrate. They often use various mechanisms, including amoeboid movement and mesenchymal migration, to move through the tissue. This migration is influenced by various signaling pathways and the tumor microenvironment.

4.Angiogenesis: As tumors grow, they require a blood supply to provide nutrients and oxygen. Tumor cells can stimulate the formation of new blood vessels (angiogenesis) through the release of growth factors like vascular endothelial growth factor (VEGF). This not only supports tumor growth but also provides a route for cancer cells to enter the bloodstream.

5.Invasion into Blood Vessels (Intravasation): Cancer cells can invade nearby blood vessels, allowing them to enter the circulatory system. This step is crucial for metastasis, as it enables cancer cells to travel to distant sites in the body.

6.Survival in Circulation: Once in the bloodstream, cancer cells must survive the immune response and the shear stress of blood flow. They can form clusters with platelets or other cells to evade detection.

7.Extravasation and Colonization: After traveling through the bloodstream, cancer cells can exit the circulation (extravasation) and invade new tissues. They may then establish secondary tumors (metastases) in distant organs.

8.Tumor Microenvironment: The surrounding microenvironment plays a significant role in tumor invasion. Factors such as immune cells, fibroblasts, and signaling molecules can either promote or inhibit invasion and metastasis.
Scientific Papers found: Click to Expand⟱
6492- Nimb,    Review on Molecular and Chemopreventive Potential of Nimbolide in Cancer
- Review, NA, NA
Apoptosis↑, TumCCA↑, TumCP↓, TumCI↓, angioG↓, TumMeta↓, PTEN↑, NF-kB↓, Wnt↓, β-catenin/ZEB1↓, IKKα↓, CXCR2↓, CXCR4↓, Bcl-2↓, COX2↓, MMP9↓, VEGF↓, TIMP2↑, chemoPv↑, ROS↑, DR4↑, P53↑, BAX↑, Casp3↑, Casp8↑, Casp9↑, cl‑PARP↑, Mcl-1↓, XIAP↓, survivin↓, FasL↑, FADD↑, EGFR↓, MMPs↓,
6489- Nimb,    Nimbolide-Induced Oxidative Stress Abrogates STAT3 Signaling Cascade and Inhibits Tumor Growth in Transgenic Adenocarcinoma of Mouse Prostate Model
- in-vivo, Pca, DU145 - in-vivo, Pca, LNCaP
tumCV↓, Apoptosis↑, TumCI↓, TumCMig↓, STAT3↓, ROS↑, TumCG↓, TumMeta↓, TumCCA↑, DNAdam↑, Casp3↑, Casp7↑, cl‑PARP↑, p‑STAT3↓, IL6↓, GSR↓,
4976- Nimb,    Nimbolide inhibits pancreatic cancer growth and metastasis through ROS-mediated apoptosis and inhibition of epithelial-to-mesenchymal transition
- vitro+vivo, PC, NA
ROS↑, Apoptosis↑, TumAuto↑, TumCP↓, TumCMig↓, TumCI↓, EMT↓, Dose↓, selectivity↑, Akt↓, eff↓, BAX↑, cl‑Casp3↑, cl‑PARP↑, Bcl-2↓,
4971- Nimb,    Nimbolide, a Neem Limonoid, Is a Promising Candidate for the Anticancer Drug Arsenal
- Review, Var, NA
TumCP↓, Apoptosis↓, TumCI↓, angioG↓, TumMeta↓, Inflam↓,

Showing Research Papers: 1 to 4 of 4

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 4

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

GSR↓, 1,   ROS↑, 3,  

Mitochondria & Bioenergetics ⓘ

XIAP↓, 1,  

Cell Death ⓘ

Akt↓, 1,   Apoptosis↓, 1,   Apoptosis↑, 3,   BAX↑, 2,   Bcl-2↓, 2,   Casp3↑, 2,   cl‑Casp3↑, 1,   Casp7↑, 1,   Casp8↑, 1,   Casp9↑, 1,   DR4↑, 1,   FADD↑, 1,   FasL↑, 1,   Mcl-1↓, 1,   survivin↓, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 1,  

Autophagy & Lysosomes ⓘ

TumAuto↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   P53↑, 1,   cl‑PARP↑, 3,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 1,   PTEN↑, 1,   STAT3↓, 1,   p‑STAT3↓, 1,   TumCG↓, 1,   Wnt↓, 1,  

Migration ⓘ

MMP9↓, 1,   MMPs↓, 1,   TIMP2↑, 1,   TumCI↓, 4,   TumCMig↓, 2,   TumCP↓, 3,   TumMeta↓, 3,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 2,   EGFR↓, 1,   VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   CXCR2↓, 1,   CXCR4↓, 1,   IKKα↓, 1,   IL6↓, 1,   Inflam↓, 1,   NF-kB↓, 1,  

Drug Metabolism & Resistance ⓘ

Dose↓, 1,   eff↓, 1,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

EGFR↓, 1,   IL6↓, 1,  

Functional Outcomes ⓘ

chemoPv↑, 1,  
Total Targets: 54

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: TumCI, Tumor Cell invasion
4 Nimbolide
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#:250  Target#:324  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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