Nimbolide / HO-1 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
HO-1, HMOX1: Click to Expand ⟱
Source:
Type:
(Also known as Hsp32 and HMOX1)
HO-1 is the common abbreviation for the protein (heme oxygenase‑1) produced by the HMOX1 gene.
HO-1 is an enzyme that plays a crucial role in various cellular processes, including the breakdown of heme, a toxic molecule. Research has shown that HO-1 is involved in the development and progression of cancer.
-widely regarded as having antioxidant and cytoprotective effects
-The overall activity of HO‑1 helps to reduce the pro‐oxidant load (by degrading free heme, a pro‑oxidant) and to generate molecules (like bilirubin) that can protect cells from oxidative damage

Studies have found that HO-1 is overexpressed in various types of cancer, including lung, breast, colon, and prostate cancer. The overexpression of HO-1 in cancer cells can contribute to their survival and proliferation by:
  Reducing oxidative stress and inflammation
  Promoting angiogenesis (the formation of new blood vessels)
  Inhibiting apoptosis (programmed cell death)
  Enhancing cell migration and invasion
When HO-1 is at a normal level, it mainly exerts an antioxidant effect, and when it is excessively elevated, it causes an accumulation of iron ions.

A proper cellular level of HMOX1 plays an antioxidative function to protect cells from ROS toxicity. However, its overexpression has pro-oxidant effects to induce ferroptosis of cells, which is dependent on intracellular iron accumulation and increased ROS content upon excessive activation of HMOX1.

-Curcumin   Activates the Nrf2 pathway leading to HO‑1 induction; known for its anti‑inflammatory and antioxidant effects.
-Resveratrol  Induces HO‑1 via activation of SIRT1/Nrf2 signaling; exhibits antioxidant and cardioprotective properties.
-Quercetin   Activates Nrf2 and related antioxidant pathways; contributes to anti‑oxidative and anti‑inflammatory responses.
-EGCG     Promotes HO‑1 expression through activation of the Nrf2/ARE pathway; also exhibits anti‑inflammatory and anticancer properties.
-Sulforaphane One of the most potent natural HO‑1 inducers; triggers Nrf2 nuclear translocation and upregulates a battery of phase II detoxifying enzymes.
-Luteolin    Induces HO‑1 via Nrf2 activation; may also exert anti‑inflammatory and neuroprotective effects in various cell models.
-Apigenin   Has been reported to induce HO‑1 expression partly via the MAPK and Nrf2 pathways; also known for anti‑inflammatory and anticancer activities.
Scientific Papers found: Click to Expand⟱
6486- Nimb,    Nimbolide: promising agent for prevention and treatment of chronic diseases
- Review, Var, NA - Review, AD, NA
*other↝, *Inflam↓, AntiCan↑, *Bacteria↓, *AntiViral↑, *neuroP↑, *hepatoP↑, *ROS?, *NRF2↑, *HO-1↑, *TLR4↓, *NF-kB↓, *AChE↓, *Aβ↓, *GSK‐3β↓, *LDL↓, *DNAdam↓, *lipid-P↓, *antiOx↑, *SOD1↑, *GSH↑, *IL6↓, *IL1β↓, *STAT3↓, *GPx↑, *Catalase↑, *MDA↓, *AntiDiabetic↑, *HDL↓, *MCP1↓, *VEGF↓, *MMP9↓, *GutMicro↑, TumCP↓, TumCCA↑, TumCMig↓, NF-kB↓, ROS↑, PI3K↓, Akt↓, mTOR↓, ERK↓, EMT↓, TumMeta↓, ChemoSen↑, eff↑, selectivity↑, CDK4↓, CDK6↓, Wnt↓, β-catenin/ZEB1↓, STAT3↓, MMP2↓, Sp1/3/4↓, AP-1↓, P21↑, *AntiArt↑, *IL23↓, *IL17↓, *IFN-γ↓, *HSP70/HSPA5↓,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

ROS↑, 1,  

Cell Death ⓘ

Akt↓, 1,  

Kinase & Signal Transduction ⓘ

Sp1/3/4↓, 1,  

Cell Cycle & Senescence ⓘ

CDK4↓, 1,   P21↑, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 1,   ERK↓, 1,   mTOR↓, 1,   PI3K↓, 1,   STAT3↓, 1,   Wnt↓, 1,  

Migration ⓘ

AP-1↓, 1,   MMP2↓, 1,   TumCMig↓, 1,   TumCP↓, 1,   TumMeta↓, 1,   β-catenin/ZEB1↓, 1,  

Immune & Inflammatory Signaling ⓘ

NF-kB↓, 1,  

Hormonal & Nuclear Receptors ⓘ

CDK6↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   eff↑, 1,   selectivity↑, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,  
Total Targets: 24

Pathway results for Effect on Normal Cells:


NA, unassigned ⓘ

AntiArt↑, 1,  

Redox & Oxidative Stress ⓘ

antiOx↑, 1,   Catalase↑, 1,   GPx↑, 1,   GSH↑, 1,   HDL↓, 1,   HO-1↑, 1,   lipid-P↓, 1,   MDA↓, 1,   NRF2↑, 1,   ROS?, 1,   SOD1↑, 1,  

Core Metabolism/Glycolysis ⓘ

LDL↓, 1,  

Transcription & Epigenetics ⓘ

other↝, 1,  

Protein Folding & ER Stress ⓘ

HSP70/HSPA5↓, 1,  

DNA Damage & Repair ⓘ

DNAdam↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

GSK‐3β↓, 1,   STAT3↓, 1,  

Migration ⓘ

MMP9↓, 1,  

Angiogenesis & Vasculature ⓘ

VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

IFN-γ↓, 1,   IL17↓, 1,   IL1β↓, 1,   IL23↓, 1,   IL6↓, 1,   Inflam↓, 1,   MCP1↓, 1,   NF-kB↓, 1,   TLR4↓, 1,  

Synaptic & Neurotransmission ⓘ

AChE↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 1,  

Clinical Biomarkers ⓘ

GutMicro↑, 1,   IL6↓, 1,  

Functional Outcomes ⓘ

AntiDiabetic↑, 1,   hepatoP↑, 1,   neuroP↑, 1,  

Infection & Microbiome ⓘ

AntiViral↑, 1,   Bacteria↓, 1,  
Total Targets: 38

Scientific Paper Hit Count for: HO-1, HMOX1
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#:597  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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