Honokiol / TumCI 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


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⟱
2881- HNK,    Honokiol Suppressed Pancreatic Cancer Progression via miR-101/Mcl-1 Axis
- in-vitro, PC, PANC1
tumCV↓, Casp3↑, Apoptosis↑, TumCCA↑, TumCI↓, Mcl-1↓, EMT↓,
2882- HNK,    Honokiol Suppresses Perineural Invasion of Pancreatic Cancer by Inhibiting SMAD2/3 Signaling
- in-vitro, PC, PANC1
TumCI↓, TumCMig↓, p‑SMAD2↓, p‑SMAD3↓, EMT↓, N-cadherin↓, Vim↓, E-cadherin↑, Snail↓, Slug↓, Rho↓, ROCK1↓,
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↓,
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↑,
1153- HNK,    Honokiol Eliminates Glioma/Glioblastoma Stem Cell-Like Cells via JAK-STAT3 Signaling and Inhibits Tumor Progression by Targeting Epidermal Growth Factor Receptor
- in-vitro, GBM, U251 - in-vitro, GBM, U87MG - in-vivo, NA, NA
tumCV↓, Apoptosis↑, TumCMig↓, TumCI↓, Bcl-2↓, EGFR↓, CD133↓, Nestin↓, Akt↓, ERK↓, Casp3↑, p‑STAT3↓, TumCG↓,
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↓,
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↓,
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↓,

Showing Research Papers: 1 to 10 of 10

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 10

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

NRF2↑, 1,   ROS↑, 1,   SIRT3↑, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,   c-Raf↓, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   ATG7↑, 1,   cMyc↓, 1,  

Cell Death ⓘ

Akt↓, 5,   Apoptosis↑, 5,   BAX↑, 1,   Bcl-2↓, 2,   Casp3↑, 4,   Casp8↑, 1,   Casp9↑, 2,   cl‑Casp9↑, 1,   cFLIP↓, 1,   Cyt‑c↑, 1,   DR5↑, 1,   JNK↑, 1,   MAPK↓, 1,   Mcl-1↓, 1,   Mcl-1↑, 1,   survivin↓, 1,  

Kinase & Signal Transduction ⓘ

cSrc↓, 1,   EF-1α↓, 1,   HER2/EBBR2↓, 1,  

Transcription & Epigenetics ⓘ

cJun↑, 1,   H3↑, 1,   H4↑, 1,   HATs↑, 1,   tumCV↓, 3,  

Protein Folding & ER Stress ⓘ

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

Autophagy & Lysosomes ⓘ

ATG5↑, 1,   LC3II↑, 1,  

DNA Damage & Repair ⓘ

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

Cell Cycle & Senescence ⓘ

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

Proliferation, Differentiation & Cell State ⓘ

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

Migration ⓘ

E-cadherin↑, 1,   MMP9↓, 4,   MMPs↓, 2,   N-cadherin↓, 1,   Rho↓, 1,   ROCK1↓, 1,   Slug↓, 1,   p‑SMAD2↓, 1,   p‑SMAD3↓, 1,   Snail↓, 1,   SOX4↓, 1,   TumCI↓, 10,   TumCMig↓, 7,   TumCP↓, 3,   TumMeta↓, 2,   Twist↓, 1,   Vim↓, 1,   Zeb1↓, 1,   α-tubulin↑, 2,   β-catenin/ZEB1↑, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   EGFR↓, 5,   Hif1a↓, 1,   VEGF↓, 2,   VEGFR2↓, 1,  

Barriers & Transport ⓘ

BBB↑, 1,   P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 3,   CXCR4↓, 1,   IKKα↓, 1,   IL1β↓, 1,   IL6↓, 1,   Inflam↓, 1,   JAK1↓, 1,   JAK2↓, 1,   NF-kB↓, 4,   p65↓, 1,   PGE2↓, 2,   TNF-α↓, 1,   TNF-α↑, 1,  

Drug Metabolism & Resistance ⓘ

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

Clinical Biomarkers ⓘ

BMPs↑, 1,   EGFR↓, 5,   HER2/EBBR2↓, 1,   IL6↓, 1,  

Functional Outcomes ⓘ

chemoP↑, 2,   OS↑, 1,   toxicity↓, 1,  
Total Targets: 131

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   Catalase↑, 1,   GSH↑, 1,   HO-1↑, 1,   NRF2↑, 1,   ROS↓, 3,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,   NADPH↓, 1,  

Cell Death ⓘ

Casp3↓, 1,  

Migration ⓘ

p‑Rac1↓, 1,  

Barriers & Transport ⓘ

BBB↑, 1,   P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

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

Clinical Biomarkers ⓘ

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

Functional Outcomes ⓘ

cardioP↑, 1,   hepatoP↑, 1,   neuroP↑, 2,   RenoP↑, 1,  
Total Targets: 28

Scientific Paper Hit Count for: TumCI, Tumor Cell invasion
10 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#:324  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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