Honokiol / toxicity Cancer Research Results

HNK, Honokiol: Click to Expand ⟱
Features:
Honokiol is a Lignan isolated from bark, seed cones and leaves of trees of Magnolia species. Honokiol was traditionally used for anxiety and stroke treatment, as well as the alleviation of flu symptoms.
-considered to have antioxidant properties
-low oral bioavailability and difficulty in intravenous administration
-the development of various formulations of honokiol, including microemulsion, liposomes, nanoparticles and micelle copolymers have successfully solved the problem of low water solubility.

Pathways:
-Inhibit NF-κB activation
-Downregulate STAT3 signalin
-Inhibiting the PI3K/Akt pathway,
-Inhibition of mTOR
-Influences various MAPK cascades—including ERK, JNK, and p38
-Inhibition of EGFR
-Inhibiting Notch pathway (CSCs)
-GPx4 inhibit
-Can induce ER stress in cancer cells, which contributes to the activation of unfolded protein response (UPR) pathways
-Disrupt the mitochondrial membrane potential in cancer cells.
-Reported to increase ROS production in cancer cells
-Can exhibit antioxidant properties in normal cells. - has some inhibitor activity but Not classified as HDAC inhibitor as weaker and may work more indirectly.
- is well-known in the research community for its role in activating SIRT3

-Note half-life 40–60 minutes
BioAv
Pathways:
- induce ROS production in cancer cells, and typically lowers ROS in normal cells
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓ Prx
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, Pro-Inflammatory Cytokines : IL-1β↓, TNF-α↓, IL-6↓,
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, VEGF↓, ROCK1↓, RhoA↓, NF-κB↓, CXCR4↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, EZH2↓, P53↑, HSP↓,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, ERK↓, EMT↓,
- inhibits glycolysis and ATP depletion : HIF-1α↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PDKs↓, ECAR↓, OXPHOS↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, EGFR↓,
- inhibits Cancer Stem Cells : CSC↓, CD133↓, β-catenin↓, sox2↓, nestin↓, OCT4↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, ERK↓, JNK, TrxR**, - Shown to modulate the nuclear translocation of SREBP-2 (related to cholesterol).
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

Rank Pathway / Axis Cancer Cells Normal Cells Label Primary Interpretation Notes
1 Mitochondrial integrity / intrinsic apoptosis ↓ ΔΨm; ↑ cytochrome-c release; ↑ caspases ↔ largely preserved Driver Mitochondria-directed cytotoxicity Honokiol directly accumulates in mitochondria and initiates intrinsic apoptosis in cancer cells
2 Reactive oxygen species (ROS) ↑ ROS (secondary, stress-amplifying) ↔ buffered Secondary Mitochondrial stress amplification ROS elevation follows mitochondrial perturbation rather than acting as the initiating trigger
3 STAT3 signaling ↓ STAT3 activation ↔ minimal Driver Loss of survival and stemness signaling STAT3 suppression contributes to apoptosis, CSC targeting, and reduced proliferation
4 PI3K → AKT → mTOR axis ↓ AKT / ↓ mTOR ↔ adaptive suppression Secondary Growth and anabolic inhibition AKT/mTOR inhibition reinforces mitochondrial and apoptotic stress
5 NF-κB signaling ↓ NF-κB activation ↓ inflammatory NF-κB tone Secondary Suppression of survival transcription NF-κB inhibition contributes to chemosensitization and anti-inflammatory effects
6 Cell cycle regulation ↑ G0/G1 or G2/M arrest ↔ spared Phenotypic Cytostatic growth control Cell-cycle arrest reflects upstream signaling disruption
7 Autophagy ↑ autophagy (context-dependent) ↑ adaptive autophagy Adaptive Stress response vs death cooperation Autophagy may precede apoptosis or act as a transient survival response


toxicity, toxicity: Click to Expand ⟱
Source:
Type:
Toxicity
Scientific Papers found: Click to Expand⟱
2895- HNK,    Mitochondria-Targeted Honokiol Confers a Striking Inhibitory Effect on Lung Cancer via Inhibiting Complex I Activity
- in-vitro, Lung, PC9
eff↑, TumCP↓, mt-ROS↑, Prx3↑, mt-STAT3↓, *toxicity∅, selectivity↑, ChemoSen↑,
2885- HNK,    Honokiol: a novel natural agent for cancer prevention and therapy
NF-kB↓, STAT3↓, EGFR↓, mTOR↓, BioAv↝, Inflam↓, TumCP↓, angioG↓, TumCI↓, TumMeta↓, cSrc↓, JAK1↓, JAK2↓, ERK↓, Akt↓, PTEN↑, ChemoSen↑, chemoP↑, COX2↓, PGE2↓, TNF-α↓, IL1β↓, IL6↓, Casp3↑, Casp8↑, Casp9↑, cl‑PARP↑, DNAdam↑, Cyt‑c↑, RadioS↑, RAS↓, BBB↑, BioAv↓, Half-Life↝, Half-Life↝, toxicity↓,
2891- HNK,    Honokiol, an Active Compound of Magnolia Plant, Inhibits Growth, and Progression of Cancers of Different Organs
- Review, Var, NA
AntiCan↑, Inflam↓, antiOx↑, selectivity↑, *toxicity↓, cycD1/CCND1↓, cycE/CCNE↓, CDK2↓, CDK4↓, TumMeta↓, NADPH↓, MMP2↓, MMP9↓, p‑mTOR↓, EGFR↓, EMT↓, SIRT1↑, SIRT3↑, EZH2↓, Snail↓, Vim↓, N-cadherin↓, E-cadherin↑, COX2↓, NF-kB↓, *ROS↓, Ca+2↑, ROS↑,
2079- HNK,    Honokiol Microemulsion Causes Stage-Dependent Toxicity Via Dual Roles in Oxidation-Reduction and Apoptosis through FoxO Signaling Pathway
- in-vitro, Nor, PC12
*toxicity↝, *ROS↓, *ROS↑, *Dose⇅, *BioAv↑, *BioAv↓, *ROS⇅, *SOD↓, *toxicity↑,
2871- HNK,    Antihyperalgesic Properties of Honokiol in Inflammatory Pain Models by Targeting of NF-κB and Nrf2 Signaling
- in-vivo, Nor, NA
*TNF-α↓, *IL1β↓, *IL6↓, *VEGF↓, *NRF2↑, *SOD2↑, *HO-1↑, *Inflam↓, *Pain↓, *NO↓, toxicity↓,
2865- HNK,    Liposomal Honokiol induces ROS-mediated apoptosis via regulation of ERK/p38-MAPK signaling and autophagic inhibition in human medulloblastoma
- in-vitro, MB, DAOY - vitro+vivo, NA, NA
BioAv↓, BioAv↓, TumCP↓, selectivity↑, P53↑, P21↑, CDK4↓, cycD1/CCND1↓, mtDam↑, ROS↑, eff↓, Casp3↑, BAX↑, LC3II↑, Beclin-1↑, ATG7↑, p62↑, eff↑, ChemoSen↑, *toxicity↓,
4521- MAG,  HNK,    Safety and Toxicology of Magnolol and Honokiol
- Review, Nor, NA
*antiOx↑, *Inflam↓, *Bacteria↓, *toxicity↓,
4526- MAG,  HNK,    Targeting apoptosis pathways in cancer with magnolol and honokiol, bioactive constituents of the bark of Magnolia officinalis
- Review, Var, NA
*antiOx↑, *Inflam↓, *Bacteria↓, *toxicity↓, AntiTum↑, Apoptosis↑, DR5↝,

Showing Research Papers: 1 to 8 of 8

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 8

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   Prx3↑, 1,   ROS↑, 2,   mt-ROS↑, 1,   SIRT3↑, 1,  

Mitochondria & Bioenergetics ⓘ

mtDam↑, 1,  

Core Metabolism/Glycolysis ⓘ

ATG7↑, 1,   NADPH↓, 1,   SIRT1↑, 1,  

Cell Death ⓘ

Akt↓, 1,   Apoptosis↑, 1,   BAX↑, 1,   Casp3↑, 2,   Casp8↑, 1,   Casp9↑, 1,   Cyt‑c↑, 1,   DR5↝, 1,  

Kinase & Signal Transduction ⓘ

cSrc↓, 1,  

Transcription & Epigenetics ⓘ

EZH2↓, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1,   LC3II↑, 1,   p62↑, 1,  

DNA Damage & Repair ⓘ

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

Cell Cycle & Senescence ⓘ

CDK2↓, 1,   CDK4↓, 2,   cycD1/CCND1↓, 2,   cycE/CCNE↓, 1,   P21↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 1,   ERK↓, 1,   mTOR↓, 1,   p‑mTOR↓, 1,   PTEN↑, 1,   RAS↓, 1,   STAT3↓, 1,   mt-STAT3↓, 1,  

Migration ⓘ

Ca+2↑, 1,   E-cadherin↑, 1,   MMP2↓, 1,   MMP9↓, 1,   N-cadherin↓, 1,   Snail↓, 1,   TumCI↓, 1,   TumCP↓, 3,   TumMeta↓, 2,   Vim↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   EGFR↓, 2,  

Barriers & Transport ⓘ

BBB↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   IL1β↓, 1,   IL6↓, 1,   Inflam↓, 2,   JAK1↓, 1,   JAK2↓, 1,   NF-kB↓, 2,   PGE2↓, 1,   TNF-α↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 3,   BioAv↝, 1,   ChemoSen↑, 3,   eff↓, 1,   eff↑, 2,   Half-Life↝, 2,   RadioS↑, 1,   selectivity↑, 3,  

Clinical Biomarkers ⓘ

EGFR↓, 2,   EZH2↓, 1,   IL6↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   AntiTum↑, 1,   chemoP↑, 1,   toxicity↓, 2,  
Total Targets: 75

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   HO-1↑, 1,   NRF2↑, 1,   ROS↓, 2,   ROS↑, 1,   ROS⇅, 1,   SOD↓, 1,   SOD2↑, 1,  

Angiogenesis & Vasculature ⓘ

NO↓, 1,   VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

IL1β↓, 1,   IL6↓, 1,   Inflam↓, 3,   TNF-α↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 1,   Dose⇅, 1,  

Clinical Biomarkers ⓘ

IL6↓, 1,  

Functional Outcomes ⓘ

Pain↓, 1,   toxicity↓, 4,   toxicity↑, 1,   toxicity↝, 1,   toxicity∅, 1,  

Infection & Microbiome ⓘ

Bacteria↓, 2,  
Total Targets: 24

Scientific Paper Hit Count for: toxicity, toxicity
8 Honokiol
2 Magnolol
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#:94  Target#:1025  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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