Honokiol / TumCCA 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


TumCCA, Tumor cell cycle arrest: Click to Expand ⟱
Source:
Type:
Tumor cell cycle arrest refers to the process by which cancer cells stop progressing through the cell cycle, which is the series of phases that a cell goes through to divide and replicate. This arrest can occur at various checkpoints in the cell cycle, including the G1, S, G2, and M phases. S, G1, G2, and M are the four phases of mitosis.
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↓,
2892- HNK,    Honokiol Induces Apoptosis, G1 Arrest, and Autophagy in KRAS Mutant Lung Cancer Cells
- in-vitro, Lung, A549 - in-vitro, Lung, H460 - in-vitro, Lung, H385 - in-vitro, Nor, BEAS-2B
TumCCA↑, Apoptosis↑, SIRT3↑, Hif1a↓, selectivity↑, p‑mTOR↓, p70S6↓,
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↑,
1004- HNK,  RAPA,    Honokiol downregulates PD-L1 expression and enhances antitumor effects of mTOR inhibitors in renal cancer cells
- in-vitro, RCC, NA
Apoptosis↑, TumCCA↑, ROS↑, PD-L1↓, IFN-γ↓,
2073- HNK,    Honokiol induces apoptosis and autophagy via the ROS/ERK1/2 signaling pathway in human osteosarcoma cells in vitro and in vivo
- in-vitro, OS, U2OS - in-vivo, NA, NA
TumCD↑, TumAuto↑, Apoptosis↑, TumCCA↑, GRP78/BiP↑, ROS↑, eff↓, p‑ERK↑, selectivity↑, Ca+2↑, MMP↓, Casp3↑, Casp9↑, cl‑PARP↑, Bcl-2↓, Bcl-xL↓, survivin↓, LC3B-II↑, ATG5↑, TumVol↓, TumW↓, ER Stress↑,
2080- HNK,    Honokiol Induces Ferroptosis by Upregulating HMOX1 in Acute Myeloid Leukemia Cells
- in-vitro, AML, THP1 - in-vitro, AML, U937 - in-vitro, AML, SK-HEP-1
tumCV↓, TumCCA↑, Ferroptosis↑, lipid-P↑, HO-1↑, GPx4∅,
2879- HNK,    Honokiol Inhibits Lung Tumorigenesis through Inhibition of Mitochondrial Function
- in-vitro, Lung, H226 - in-vivo, NA, NA
tumCV↓, selectivity↑, TumCP↓, TumCCA↑, Apoptosis↑, mt-ROS↑, Casp3↑, Casp7↑, OCR↓, Cyt‑c↑, ATP↓, mitResp↓, AMP↑, AMPK↑,
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↓,
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 9 of 9

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 9

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Ferroptosis↑, 1,   GPx4∅, 1,   HO-1↑, 1,   lipid-P↑, 1,   NRF2↑, 1,   ROS↑, 3,   mt-ROS↑, 1,   SIRT3↑, 2,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 1,   mitResp↓, 1,   MMP↓, 2,   OCR↓, 1,   c-Raf↓, 1,  

Core Metabolism/Glycolysis ⓘ

AMP↑, 1,   AMPK↑, 2,   ATG7↑, 1,   cMyc↓, 1,  

Cell Death ⓘ

Akt↓, 1,   Apoptosis↑, 6,   Bcl-2↓, 1,   Bcl-xL↓, 1,   Casp3↑, 4,   Casp7↑, 1,   Casp9↑, 2,   Cyt‑c↑, 1,   DR5↑, 1,   Ferroptosis↑, 1,   JNK↑, 1,   MAPK↓, 1,   Mcl-1↓, 1,   Mcl-1↑, 1,   survivin↓, 2,   TumCD↑, 1,  

Kinase & Signal Transduction ⓘ

EF-1α↓, 1,   HER2/EBBR2↓, 1,   p70S6↓, 1,  

Transcription & Epigenetics ⓘ

cJun↑, 1,   H3↑, 1,   ac‑H3↑, 1,   H4↑, 1,   ac‑H4↑, 1,   HATs↑, 1,   tumCV↓, 4,  

Protein Folding & ER Stress ⓘ

cl‑CHOP↑, 1,   ER Stress↑, 2,   GRP78/BiP↑, 2,  

Autophagy & Lysosomes ⓘ

ATG5↑, 2,   LC3B-II↑, 1,   LC3II↑, 1,   TumAuto↑, 1,  

DNA Damage & Repair ⓘ

P53↑, 1,   cl‑PARP↑, 2,   PCNA↓, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 2,   CDK4↓, 2,   cycD1/CCND1↓, 2,   P21?, 1,   P21↑, 1,   p‑RB1↓, 1,   TumCCA↑, 9,  

Proliferation, Differentiation & Cell State ⓘ

CD133↓, 1,   CSCs↓, 1,   EMT↓, 2,   p‑ERK↑, 1,   HDAC↓, 2,   p‑mTOR↓, 1,   mTORC1↓, 1,   Nanog↓, 1,   Nestin↓, 1,   NOTCH1↓, 1,   NOTCH3↓, 1,   OCT4↓, 1,   PI3K↓, 2,   SOX2↓, 1,   STAT3↓, 1,  

Migration ⓘ

Ca+2↑, 1,   MMP9↓, 1,   MMPs↓, 1,   SOX4↓, 1,   TumCI↓, 3,   TumCMig↓, 2,   TumCP↓, 2,   TumMeta↓, 1,   Zeb1↓, 1,   β-catenin/ZEB1↑, 1,  

Angiogenesis & Vasculature ⓘ

Hif1a↓, 2,   VEGFR2↓, 1,  

Barriers & Transport ⓘ

P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IFN-γ↓, 1,   IKKα↓, 1,   NF-kB↓, 1,   p65↓, 1,   PD-L1↓, 1,   PGE2↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   ChemoSen↑, 1,   Dose↝, 1,   eff↓, 1,   eff↑, 1,   Half-Life↓, 1,   Half-Life↝, 1,   selectivity↑, 5,  

Clinical Biomarkers ⓘ

HER2/EBBR2↓, 1,   PD-L1↓, 1,  

Functional Outcomes ⓘ

OS↑, 1,   TumVol↓, 1,   TumW↓, 1,  
Total Targets: 108

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   ROS↓, 1,  

Barriers & Transport ⓘ

BBB↑, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,  

Functional Outcomes ⓘ

neuroP↑, 1,  
Total Targets: 5

Scientific Paper Hit Count for: TumCCA, Tumor cell cycle arrest
9 Honokiol
1 Rapamycin
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#:322  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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