Honokiol / cycD1/CCND1 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


cycD1/CCND1, cyclin D1 pathway: Click to Expand ⟱
Source:
Type:
Also called CCND1 Gatekeeper of Cell-Cycle Commitment
The main function of cyclin D1 is to maintain cell cycle and to promote cell proliferation. Cyclin D1 is a key regulatory protein involved in the cell cycle, particularly in the transition from the G1 phase to the S phase. It is part of the cyclin-dependent kinase (CDK) complex, where it binds to CDK4 or CDK6 to promote cell cycle progression.
Cyclin D1 is crucial for the regulation of the cell cycle. Overexpression or dysregulation of cyclin D1 can lead to uncontrolled cell proliferation, a hallmark of cancer.
Cyclin D1 is often found to be overexpressed in various cancers.
Cyclin D1 can interact with tumor suppressor proteins, such as retinoblastoma (Rb). When cyclin D1 is overexpressed, it can lead to the phosphorylation and inactivation of Rb, releasing E2F transcription factors that promote the expression of genes required for DNA synthesis and cell cycle progression.
Cyclin D1 is influenced by various signaling pathways, including the PI3K/Akt and MAPK pathways, which are often activated in cancer.
In some cancers, high levels of cyclin D1 expression have been associated with poor prognosis, making it a potential biomarker for cancer progression and treatment response.
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↑,
2894- HNK,    Pharmacological features, health benefits and clinical implications of honokiol
- Review, Var, NA - Review, AD, NA
*BioAv↓, *neuroP↑, *BBB↑, *ROS↓, *Keap1↑, *NRF2↑, *Casp3↓, *SIRT3↑, *Rho↓, *ERK↓, *NF-kB↓, angioG↓, RAS↓, PI3K↓, Akt↓, mTOR↓, *memory↑, *Aβ↓, *PPARγ↑, *PGC-1α↑, NF-kB↓, Hif1a↓, VEGF↓, HO-1↓, FOXM1↓, p27↑, P21↑, CDK2↓, CDK4↓, CDK6↓, cycD1/CCND1↓, Twist↓, MMP2↓, Rho↑, ROCK1↑, TumCMig↓, cFLIP↓, BMPs↑, OCR↑, ECAR↓, *AntiAg↑, *cardioP↑, *antiOx↑, *ROS↓, P-gp↓,
4523- HNK,  MAG,  BA,    Honokiol-Magnolol-Baicalin Possesses Synergistic Anticancer Potential and Enhances the Efficacy of Anti-PD-1 Immunotherapy in Colorectal Cancer by Triggering GSDME-Dependent Pyroptosis
- in-vitro, CRC, HCT116 - in-vitro, CRC, LoVo - in-vivo, CRC, HCT116
AntiCan↑, eff↑, TumCP↓, TumCCA↓, cycD1/CCND1↓, Pyro↑, Apoptosis↑, cl‑GSDME↑, Bcl-2↓, Cyt‑c↑, Casp9↑, TumCG↓,
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↓,
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↓,

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,   HO-1↓, 1,   NRF2↑, 1,   ROS↑, 3,   SIRT3↑, 2,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,   mtDam↑, 1,   OCR↑, 1,   c-Raf↓, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   ATG7↑, 2,   cMyc↓, 1,   ECAR↓, 1,   NADPH↓, 1,   SIRT1↑, 1,  

Cell Death ⓘ

Akt↓, 1,   Apoptosis↑, 1,   BAX↑, 1,   Bcl-2↓, 1,   Casp3↑, 2,   Casp9↑, 2,   cFLIP↓, 1,   Cyt‑c↑, 1,   DR5↑, 1,   cl‑GSDME↑, 1,   JNK↑, 1,   MAPK↓, 1,   Mcl-1↑, 1,   p27↑, 1,   Pyro↑, 1,   survivin↓, 1,  

Kinase & Signal Transduction ⓘ

EF-1α↓, 1,  

Transcription & Epigenetics ⓘ

cJun↑, 1,   EZH2↓, 1,   H3↑, 1,   ac‑H3↑, 1,   H4↑, 1,   ac‑H4↑, 1,   HATs↑, 1,   tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

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

Autophagy & Lysosomes ⓘ

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

DNA Damage & Repair ⓘ

P53↑, 2,   cl‑PARP↑, 1,   PCNA↓, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 4,   CDK4↓, 5,   cycD1/CCND1↓, 6,   cycE/CCNE↓, 1,   P21?, 1,   P21↑, 2,   p‑RB1↓, 1,   TumCCA↓, 1,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

CD133↓, 1,   CSCs↓, 1,   EMT↓, 2,   FOXM1↓, 1,   HDAC↓, 2,   mTOR↓, 1,   p‑mTOR↓, 1,   mTORC1↓, 1,   Nanog↓, 1,   Nestin↓, 1,   NOTCH1↓, 1,   NOTCH3↓, 1,   OCT4↓, 1,   PI3K↓, 2,   RAS↓, 1,   SOX2↓, 1,   STAT3↓, 1,   TumCG↓, 1,  

Migration ⓘ

Ca+2↑, 1,   E-cadherin↑, 1,   MMP2↓, 2,   MMP9↓, 1,   MMPs↓, 1,   N-cadherin↓, 1,   Rho↑, 1,   ROCK1↑, 1,   Snail↓, 1,   SOX4↓, 1,   TumCI↓, 1,   TumCMig↓, 2,   TumCP↓, 2,   TumMeta↓, 2,   Twist↓, 1,   Vim↓, 1,   Zeb1↓, 1,   β-catenin/ZEB1↑, 1,  

Angiogenesis & Vasculature ⓘ

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

Barriers & Transport ⓘ

P-gp↓, 2,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   IKKα↓, 1,   Inflam↓, 1,   NF-kB↓, 3,   p65↓, 1,   PGE2↓, 1,  

Hormonal & Nuclear Receptors ⓘ

CDK6↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 3,   ChemoSen↑, 2,   Dose↝, 1,   eff↓, 1,   eff↑, 3,   Half-Life↓, 1,   Half-Life↝, 1,   selectivity↑, 4,  

Clinical Biomarkers ⓘ

BMPs↑, 1,   EGFR↓, 1,   EZH2↓, 1,   FOXM1↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 2,   OS↑, 1,  
Total Targets: 122

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   Keap1↑, 1,   NRF2↑, 1,   ROS↓, 4,   SIRT3↑, 1,  

Mitochondria & Bioenergetics ⓘ

PGC-1α↑, 1,  

Core Metabolism/Glycolysis ⓘ

PPARγ↑, 1,  

Cell Death ⓘ

Casp3↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 1,  

Migration ⓘ

AntiAg↑, 1,   Rho↓, 1,  

Barriers & Transport ⓘ

BBB↑, 2,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,   NF-kB↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 1,   memory↑, 1,   neuroP↑, 2,   toxicity↓, 2,  
Total Targets: 20

Scientific Paper Hit Count for: cycD1/CCND1, cyclin D1 pathway
6 Honokiol
1 Magnolol
1 Baicalin
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#:73  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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