Honokiol / MMP9 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


MMP9, MMP9: Click to Expand ⟱
Source: HalifaxProj(suppress)
Type:
Matrix metalloproteinase-9 (MMP-9) is an enzyme that plays a significant role in the degradation of extracellular matrix components.
MMP-9 facilitates the breakdown of the extracellular matrix, which can enable cancer cells to invade surrounding tissues and spread to distant sites (metastasis).
Elevated levels of MMP-9 have been associated with poor prognosis in several cancers, including breast, lung, and colorectal cancers.
MMP2 and MMP9: two enzymes are critical to tumor invasion.
Scientific Papers found: Click to Expand⟱
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↑,
2897- HNK,    Honokiol Inhibits Proliferation, Invasion and Induces Apoptosis Through Targeting Lyn Kinase in Human Lung Adenocarcinoma Cells
- in-vitro, Lung, PC9 - in-vitro, Lung, A549
TumCP↓, Apoptosis↑, EGFR↓, PI3K↓, Akt↓, STAT3↓, TumCI↓, TNF-α↑, NF-kB↓, VEGF↓, MMP9↓, COX2↓,
2898- HNK,    Honokiol Suppression of Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Gastric Cancer Cell Biological Activity and Its Mechanism
- in-vitro, GC, AGS - in-vitro, GC, NCI-N87 - in-vitro, BC, MGC803 - in-vitro, GC, SGC-7901
TumCP↓, Apoptosis↑, TumCI↓, TumCMig↓, HER2/EBBR2↓, TumCCA↑, PI3K↓, Akt↓, MMP9↓, P21↑,
1087- HNK,    Honokiol Inhibits Non-Small Cell Lung Cancer Cell Migration by Targeting PGE2-Mediated Activation of β-Catenin Signaling
- in-vitro, Lung, A549 - in-vitro, Lung, H1299 - in-vitro, Lung, H460 - in-vitro, Lung, H226
TumCMig↓, COX2↓, PGE2↓, NF-kB↓, p65↓, β-catenin/ZEB1↓, MMP2↓, MMP9↓,
2878- 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
TumCMig↓, TumCI↓, MMP9↓, α-tubulin↑, HDAC6↓, HSP90↓,
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↓,

Showing Research Papers: 1 to 6 of 6

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 6

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   ROS↑, 1,   SIRT3↑, 1,  

Core Metabolism/Glycolysis ⓘ

NADPH↓, 1,   SIRT1↑, 1,  

Cell Death ⓘ

Akt↓, 2,   Apoptosis↑, 2,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 1,  

Transcription & Epigenetics ⓘ

EZH2↓, 1,  

Protein Folding & ER Stress ⓘ

HSP90↓, 2,  

Cell Cycle & Senescence ⓘ

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

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 1,   HDAC6↓, 2,   p‑mTOR↓, 1,   PI3K↓, 2,   STAT3↓, 1,  

Migration ⓘ

Ca+2↑, 1,   E-cadherin↑, 1,   MMP2↓, 2,   MMP9↓, 6,   N-cadherin↓, 1,   Snail↓, 1,   TumCI↓, 4,   TumCMig↓, 4,   TumCP↓, 2,   TumMeta↓, 1,   Vim↓, 1,   α-tubulin↑, 2,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

EGFR↓, 3,   VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 3,   Inflam↓, 1,   NF-kB↓, 3,   p65↓, 1,   PGE2↓, 1,   TNF-α↑, 1,  

Drug Metabolism & Resistance ⓘ

selectivity↑, 1,  

Clinical Biomarkers ⓘ

EGFR↓, 3,   EZH2↓, 1,   HER2/EBBR2↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,  
Total Targets: 47

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

ROS↓, 1,  

Functional Outcomes ⓘ

toxicity↓, 1,  
Total Targets: 2

Scientific Paper Hit Count for: MMP9, MMP9
6 Honokiol
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#:203  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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