Honokiol 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


Scientific Papers found: Click to Expand⟱
2877- HNK,    Targeting histone deacetylase-3 blocked epithelial-mesenchymal plasticity and metastatic dissemination in gastric cancer
- in-vitro, GC, AGS
HDAC3↓, NF-kB↓, CEBPB↓, ER Stress↑, EMT↓, Wnt↓, β-catenin/ZEB1↓,
2876- HNK,    Honokiol from Magnolia spp. induces G1 arrest via disruption of EGFR stability through repressing HDAC6 deacetylated Hsp90 function in lung cancer cells
- in-vitro, Lung, A549 - in-vitro, Lung, H23 - in-vitro, Lung, HCC827
EGFR↓, HSP90↓,
2875- HNK,    Inhibition of class I histone deacetylases in non-small cell lung cancer by honokiol leads to suppression of cancer cell growth and induction of cell death in vitro and in vivo
- in-vitro, Lung, A549 - in-vitro, Lung, H1299 - in-vitro, Lung, H460 - in-vitro, SCC, H226
HDAC↓, tumCV↓, TumCCA↑, cycD1/CCND1↓, ac‑H3↑, ac‑H4↑, selectivity↑, CDK2↓, CDK4↓,
2874- HNK,    Suppressing migration and invasion of H1299 lung cancer cells by honokiol through disrupting expression of an HDAC6‐mediated matrix metalloproteinase 9
- in-vitro, Lung, H1299
MMP9↓, α-tubulin↑, TumCI↓, HDAC6↓, HSP90↓, TumCMig↓, EGFR↓,
2873- HNK,    Honokiol Alleviates Oxidative Stress-Induced Neurotoxicity via Activation of Nrf2
- in-vitro, Nor, PC12
*neuroP↑, *GSH↑, *HO-1↑, *NADPH↑, *Trx1↑, *TrxR1↑, *NRF2↑, *ROS↓, *antiOx↑, *BBB↑, Dose↓,
2863- HNK,    Honokiol induces paraptosis-like cell death through mitochondrial ROS-dependent endoplasmic reticulum stress in hepatocellular carcinoma Hep3B cells
- in-vitro, Liver, Hep3B
ER Stress↑, Ca+2↑, mtDam↑, PTEN↑, PARK2↑, Alix/AIP‑1↓, ROS↑, mt-ROS↑,
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↓,
2870- HNK,    Honokiol attenuates oxidative stress and vascular calcification via the upregulation of heme oxygenase-1 in chronic kidney disease
- in-vitro, CKD, NA
*HO-1↑, *ROS↓,
2869- HNK,    Nature's neuroprotector: Honokiol and its promise for Alzheimer's and Parkinson's
- Review, AD, NA - Review, Park, NA
*neuroP↑, *Inflam↓, *motorD↑, *Aβ↓, *p‑tau↓, *cognitive↑, *memory↑, *ERK↑, *p‑Akt↑, *PPARγ↑, *PGC-1α↑, *MMP↑, *mt-ROS↓, *SIRT3↑, *IL1β↓, *TNF-α↓, *GRP78/BiP↓, *CHOP↓, *NF-kB↓, *GSK‐3β↓, *β-catenin/ZEB1↑, *Ca+2↓, *AChE↓, *SOD↑, *Catalase↑, *GPx↑,
2868- HNK,    Honokiol: A review of its pharmacological potential and therapeutic insights
- Review, Var, NA - Review, Sepsis, NA
*P-gp↓, *ROS↓, *TNF-α↓, *IL10↓, *IL6↓, eIF2α↑, CHOP↑, GRP78/BiP↑, BAX↑, cl‑Casp9↑, p‑PERK↑, ER Stress↑, Apoptosis↑, MMPs↓, cFLIP↓, CXCR4↓, Twist↓, HDAC↓, BMPs↑, p‑STAT3↓, mTOR↓, EGFR↓, NF-kB↓, Shh↓, VEGF↓, tumCV↓, TumCMig↓, TumCI↓, ERK↓, Akt↓, Bcl-2↓, Nestin↓, CD133↓, p‑cMET↑, RAS↑, chemoP↑, *NRF2↑, *NADPH↓, *p‑Rac1↓, *ROS↓, *IKKα↑, *NF-kB↓, *COX2↓, *PGE2↓, *Casp3↓, *hepatoP↑, *antiOx↑, *GSH↑, *Catalase↑, *RenoP↑, *ALP↓, *AST↓, *ALAT↓, *neuroP↑, *cardioP↑, *HO-1↑, *Inflam↓,
2867- HNK,    Honokiol ameliorates oxidative stress-induced DNA damage and apoptosis of c2c12 myoblasts by ROS generation and mitochondrial pathway
- in-vitro, Nor, C2C12
*antiOx↑, *ROS↓, *Bcl-2↑, *BAX↓, Casp9∅, Casp3∅, cl‑PARP∅, Cyt‑c?,
2866- HNK,    Honokiol and its analogues as anticancer compounds: Current mechanistic insights and structure-activity relationship
- Review, Var, NA
EMT↓, TumMeta↓, BioAv↑, BBB↑,
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↓,
2864- HNK,    Honokiol: A Review of Its Anticancer Potential and Mechanisms
- Review, Var, NA
TumCCA↑, CDK2↓, EMT↓, MMPs↓, AMPK↑, TumCI↓, TumCMig↓, TumMeta↓, VEGFR2↓, *antiOx↑, *Inflam↓, *BBB↑, *neuroP↑, *ROS↓, Dose↝, selectivity↑, Casp3↑, Casp9↑, NOTCH1↓, cycD1/CCND1↓, cMyc↓, P21?, DR5↑, cl‑PARP↑, P53↑, Mcl-1↑, p65↓, NF-kB↓, ROS↑, JNK↑, NRF2↑, cJun↑, EF-1α↓, MAPK↓, PI3K↓, mTORC1↓, CSCs↓, OCT4↓, Nanog↓, SOX4↓, STAT3↓, CDK4↓, p‑RB1↓, PGE2↓, COX2↓, β-catenin/ZEB1↑, IKKα↓, HDAC↓, HATs↑, H3↑, H4↑, LC3II↑, c-Raf↓, SIRT3↑, Hif1a↓, ER Stress↑, GRP78/BiP↑, cl‑CHOP↑, MMP↓, PCNA↓, Zeb1↓, NOTCH3↓, CD133↓, Nestin↓, ATG5↑, ATG7↑, survivin↓, ChemoSen↑, SOX2↓, OS↑, P-gp↓, Half-Life↓, Half-Life↝, eff↑, BioAv↓,
4521- MAG,  HNK,    Safety and Toxicology of Magnolol and Honokiol
- Review, Nor, NA
*antiOx↑, *Inflam↓, *Bacteria↓, *toxicity↓,
4525- MAG,  HNK,    Magnolol and Honokiol: Two Natural Compounds with Similar Chemical Structure but Different Physicochemical and Stability Properties
- Study, Nor, NA
*BioAv↝, *eff↑,
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: 51 to 67 of 67
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* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 67

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

NRF2↑, 1,   PARK2↑, 1,   ROS↑, 3,   mt-ROS↑, 1,   SIRT3↑, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,   mtDam↑, 2,   c-Raf↓, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   ATG7↑, 2,   cMyc↓, 1,  

Cell Death ⓘ

Akt↓, 1,   Apoptosis↑, 2,   BAX↑, 2,   Bcl-2↓, 1,   Casp3↑, 2,   Casp3∅, 1,   Casp9↑, 1,   Casp9∅, 1,   cl‑Casp9↑, 1,   cFLIP↓, 1,   Cyt‑c?, 1,   DR5↑, 1,   DR5↝, 1,   JNK↑, 1,   MAPK↓, 1,   Mcl-1↑, 1,   survivin↓, 1,  

Kinase & Signal Transduction ⓘ

EF-1α↓, 1,  

Transcription & Epigenetics ⓘ

cJun↑, 1,   H3↑, 1,   ac‑H3↑, 1,   H4↑, 1,   ac‑H4↑, 1,   HATs↑, 1,   tumCV↓, 2,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   cl‑CHOP↑, 1,   eIF2α↑, 1,   ER Stress↑, 4,   GRP78/BiP↑, 2,   HSP90↓, 2,   p‑PERK↑, 1,  

Autophagy & Lysosomes ⓘ

ATG5↑, 1,   Beclin-1↑, 1,   LC3II↑, 2,   p62↑, 1,  

DNA Damage & Repair ⓘ

P53↑, 2,   cl‑PARP↑, 1,   cl‑PARP∅, 1,   PCNA↓, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 2,   CDK4↓, 3,   cycD1/CCND1↓, 3,   P21?, 1,   P21↑, 1,   p‑RB1↓, 1,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

CD133↓, 2,   CEBPB↓, 1,   p‑cMET↑, 1,   CSCs↓, 1,   EMT↓, 3,   ERK↓, 1,   HDAC↓, 3,   HDAC3↓, 1,   HDAC6↓, 1,   mTOR↓, 1,   mTORC1↓, 1,   Nanog↓, 1,   Nestin↓, 2,   NOTCH1↓, 1,   NOTCH3↓, 1,   OCT4↓, 1,   PI3K↓, 1,   PTEN↑, 1,   RAS↑, 1,   Shh↓, 1,   SOX2↓, 1,   STAT3↓, 1,   p‑STAT3↓, 1,   Wnt↓, 1,  

Migration ⓘ

Alix/AIP‑1↓, 1,   Ca+2↑, 1,   MMP9↓, 1,   MMPs↓, 2,   SOX4↓, 1,   TumCI↓, 3,   TumCMig↓, 3,   TumCP↓, 1,   TumMeta↓, 2,   Twist↓, 1,   Zeb1↓, 1,   α-tubulin↑, 1,   β-catenin/ZEB1↓, 1,   β-catenin/ZEB1↑, 1,  

Angiogenesis & Vasculature ⓘ

EGFR↓, 3,   Hif1a↓, 1,   VEGF↓, 1,   VEGFR2↓, 1,  

Barriers & Transport ⓘ

BBB↑, 1,   P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   CXCR4↓, 1,   IKKα↓, 1,   NF-kB↓, 3,   p65↓, 1,   PGE2↓, 1,  

Drug Metabolism & Resistance ⓘ

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

Clinical Biomarkers ⓘ

BMPs↑, 1,   EGFR↓, 3,  

Functional Outcomes ⓘ

AntiTum↑, 1,   chemoP↑, 1,   OS↑, 1,   toxicity↓, 1,  
Total Targets: 124

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 6,   Catalase↑, 2,   GPx↑, 1,   GSH↑, 2,   HO-1↑, 4,   NRF2↑, 3,   ROS↓, 6,   mt-ROS↓, 1,   SIRT3↑, 1,   SOD↑, 1,   SOD2↑, 1,   Trx1↑, 1,   TrxR1↑, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↑, 1,   PGC-1α↑, 1,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,   NADPH↓, 1,   NADPH↑, 1,   PPARγ↑, 1,  

Cell Death ⓘ

p‑Akt↑, 1,   BAX↓, 1,   Bcl-2↑, 1,   Casp3↓, 1,  

Protein Folding & ER Stress ⓘ

CHOP↓, 1,   GRP78/BiP↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↑, 1,   GSK‐3β↓, 1,  

Migration ⓘ

Ca+2↓, 1,   p‑Rac1↓, 1,   β-catenin/ZEB1↑, 1,  

Angiogenesis & Vasculature ⓘ

NO↓, 1,   VEGF↓, 1,  

Barriers & Transport ⓘ

BBB↑, 2,   P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IKKα↑, 1,   IL10↓, 1,   IL1β↓, 2,   IL6↓, 2,   Inflam↓, 6,   NF-kB↓, 2,   PGE2↓, 1,   TNF-α↓, 3,  

Synaptic & Neurotransmission ⓘ

AChE↓, 1,   p‑tau↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↝, 1,   eff↑, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   ALP↓, 1,   AST↓, 1,   IL6↓, 2,  

Functional Outcomes ⓘ

cardioP↑, 1,   cognitive↑, 1,   hepatoP↑, 1,   memory↑, 1,   motorD↑, 1,   neuroP↑, 4,   Pain↓, 1,   RenoP↑, 1,   toxicity↓, 3,  

Infection & Microbiome ⓘ

Bacteria↓, 2,  
Total Targets: 62

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

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