Honokiol / Akt 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


Akt, PKB-Protein kinase B: Click to Expand ⟱
Source: HalifaxProj(inhibit)
Type:
Akt1 is involved in cellular survival pathways, by inhibiting apoptotic processes; Akt2 is an important signaling molecule in the insulin signaling pathway. It is required to induce glucose transport.

Inhibitors:
-Curcumin: downregulate AKT phosphorylation and signaling.
-Resveratrol
-Quercetin: inhibit the PI3K/AKT pathway.
-Epigallocatechin Gallate (EGCG)
-Luteolin and Apigenin: inhibit AKT phosphorylation


Scientific Papers found: Click to Expand⟱
2883- HNK,    Honokiol targets mitochondria to halt cancer progression and metastasis
- Review, Var, NA
ChemoSen↑, BBB↓, Ca+2↑, Cyt‑c↑, Casp3↑, chemoPv↑, OCR↓, mitResp↓, Apoptosis↑, RadioS↑, NF-kB↓, Akt↓, TNF-α↓, PGE2↓, VEGF↓, NO↝, COX2↓, RAS↓, EMT↓, Snail↓, N-cadherin↓, β-catenin/ZEB1↓, E-cadherin↑, ER Stress↑, p‑STAT3↓, EGFR↓, mTOR↓, mt-ROS↑, PI3K↓, Wnt↓,
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↓,
2886- HNK,    Liposomal honokiol inhibits non-small cell lung cancer progression and enhances PD-1 blockade via suppressing M2 macrophages polarization
- in-vitro, Lung, A549 - in-vitro, Lung, H460 - in-vivo, NA, NA
eff↑, BioAv↑, eff↑, PI3K↓, Akt↓,
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↓,
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↑,
4688- HNK,    Honokiol Suppresses Renal Cancer Cells’ Metastasis via Dual-Blocking Epithelial-Mesenchymal Transition and Cancer Stem Cell Properties through Modulating miR-141/ZEB2 Signaling
- vitro+vivo, RCC, A498
CSCs↓, EMT↓, TumCG↓, PI3K↓, Akt↓, mTOR↓, p‑Akt↓, PTEN↑, Wnt↓, β-catenin/ZEB1↓,
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↓,
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↓,

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 ⓘ

HO-1↓, 1,   mt-ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

mitResp↓, 1,   OCR↓, 1,   OCR↑, 1,  

Core Metabolism/Glycolysis ⓘ

ECAR↓, 1,  

Cell Death ⓘ

Akt↓, 9,   p‑Akt↓, 1,   Apoptosis↑, 5,   BAX↑, 1,   Bcl-2↓, 2,   Casp3↑, 3,   Casp8↑, 1,   Casp9↑, 1,   cl‑Casp9↑, 1,   cFLIP↓, 2,   Cyt‑c↑, 2,   p27↑, 1,  

Kinase & Signal Transduction ⓘ

cSrc↓, 1,   HER2/EBBR2↓, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 2,  

Protein Folding & ER Stress ⓘ

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

DNA Damage & Repair ⓘ

DNAdam↑, 1,   cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 1,   CDK4↓, 1,   cycD1/CCND1↓, 1,   P21↑, 2,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

CD133↓, 2,   p‑cMET↑, 1,   CSCs↓, 1,   EMT↓, 2,   ERK↓, 3,   FOXM1↓, 1,   HDAC↓, 1,   mTOR↓, 5,   Nestin↓, 2,   PI3K↓, 6,   PTEN↑, 2,   RAS↓, 3,   RAS↑, 1,   Shh↓, 1,   STAT3↓, 2,   p‑STAT3↓, 3,   TumCG↓, 2,   Wnt↓, 2,  

Migration ⓘ

Ca+2↑, 1,   E-cadherin↑, 1,   MMP2↓, 1,   MMP9↓, 2,   MMPs↓, 1,   N-cadherin↓, 1,   Rho↑, 1,   ROCK1↑, 1,   Snail↓, 1,   TumCI↓, 5,   TumCMig↓, 4,   TumCP↓, 3,   TumMeta↓, 1,   Twist↓, 2,   β-catenin/ZEB1↓, 2,  

Angiogenesis & Vasculature ⓘ

angioG↓, 2,   EGFR↓, 5,   Hif1a↓, 1,   NO↝, 1,   VEGF↓, 4,  

Barriers & Transport ⓘ

BBB↓, 1,   BBB↑, 1,   P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 3,   CXCR4↓, 1,   IL1β↓, 1,   IL6↓, 1,   Inflam↓, 1,   JAK1↓, 1,   JAK2↓, 1,   NF-kB↓, 5,   PGE2↓, 2,   TNF-α↓, 2,   TNF-α↑, 1,  

Hormonal & Nuclear Receptors ⓘ

CDK6↓, 1,  

Drug Metabolism & Resistance ⓘ

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

Clinical Biomarkers ⓘ

BMPs↑, 2,   EGFR↓, 5,   FOXM1↓, 1,   HER2/EBBR2↓, 1,   IL6↓, 1,  

Functional Outcomes ⓘ

chemoP↑, 2,   chemoPv↑, 1,   toxicity↓, 1,  
Total Targets: 101

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   Catalase↑, 2,   GPx↑, 1,   GSH↑, 1,   HO-1↑, 1,   Keap1↑, 1,   NRF2↑, 2,   ROS↓, 4,   mt-ROS↓, 1,   SIRT3↑, 2,   SOD↑, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↑, 1,   PGC-1α↑, 2,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,   NADPH↓, 1,   PPARγ↑, 2,  

Cell Death ⓘ

p‑Akt↑, 1,   Casp3↓, 2,  

Protein Folding & ER Stress ⓘ

CHOP↓, 1,   GRP78/BiP↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 1,   ERK↑, 1,   GSK‐3β↓, 1,  

Migration ⓘ

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

Barriers & Transport ⓘ

BBB↑, 1,   P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

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

Synaptic & Neurotransmission ⓘ

AChE↓, 1,   p‑tau↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 2,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,  

Clinical Biomarkers ⓘ

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

Functional Outcomes ⓘ

cardioP↑, 2,   cognitive↑, 1,   hepatoP↑, 1,   memory↑, 2,   motorD↑, 1,   neuroP↑, 3,   RenoP↑, 1,  
Total Targets: 54

Scientific Paper Hit Count for: Akt, PKB-Protein kinase B
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#:4  State#:%  Dir#:%
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