Honokiol / SIRT3 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


SIRT3, Sirtuin 3: Click to Expand ⟱
Source:
Type:
SIRT3 (Sirtuin 3) is a protein that is a member of the sirtuin family of proteins, which are involved in various cellular processes, including metabolism, stress resistance, and longevity.
In general, low SIRT3 expression is associated with:
-Poor prognosis, Increased tumor size, Metastasis, Resistance to chemotherapy and radiation therapy, Poor response to treatment.
High SIRT3 expression is associated with:
-Better prognosis, Smaller tumor size, Less metastasis, Better response to chemotherapy and radiation therapy, Better response to treatment.
SIRT3 also functions as a tumor suppressor by targeting the mitochondrial enzyme manganese superoxide dismutase (MnSOD), decreasing reactive oxygen species (ROS) production and maintaining genomic stability.
Scientific Papers found: Click to Expand⟱
2889- HNK,  doxoR,    Honokiol, an activator of Sirtuin-3 (SIRT3) preserves mitochondria and protects the heart from doxorubicin-induced cardiomyopathy in mice
- in-vivo, Nor, NA
*SIRT3↑, chemoP↑, *cardioP↑, mtDam↑, ROS↑, *ROS↓, *MMP↑,
2890- HNK,    SIRT3 activation promotes enteric neurons survival and differentiation
*SIRT3↑, *antiOx↑, *neuroP↑,
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↑,
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↓,
2893- HNK,  doxoR,    Honokiol protects against doxorubicin cardiotoxicity via improving mitochondrial function in mouse hearts
- in-vivo, Nor, NA
*mitResp↑, *PPARγ↑, *cardioP↑, *SIRT3↑, *ROS↓, *GSH↑, *SOD2↑,
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↓,
2899- HNK,    SIRT3 activator honokiol ameliorates surgery/anesthesia-induced cognitive decline in mice through anti-oxidative stress and anti-inflammatory in hippocampus
- in-vivo, Nor, NA
*memory↑, *Inflam↓, *ROS↓, neuroP↑, SIRT3↑, ac‑SOD2↓,
2900- HNK,    The Role and Therapeutic Perspectives of Sirtuin 3 in Cancer Metabolism Reprogramming, Metastasis, and Chemoresistance
- Review, Var, NA
SIRT3↑, Hif1a↓, ChemoSen↑, chemoP↑,
4238- HNK,    Neuropharmacological potential of honokiol and its derivatives from Chinese herb Magnolia species: understandings from therapeutic viewpoint
- Review, AD, NA - NA, Park, NA
*BDNF↑, *hepatoP↑, *ALAT↓, *AST↓, *TNF-α↓, *SIRT3↑, *Aβ↓, *Apoptosis↓, *ROS↓, *MMP↑, *Ca+2↓, *Casp3↓, *Ach↑, *PPARγ↑, *PGC-1α↑, *motorD↑, *TNF-α↓, *IL1β↓,
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↑,
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 11 of 11

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 11

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   HO-1↓, 1,   NRF2↑, 1,   ROS↑, 3,   SIRT3↑, 5,   ac‑SOD2↓, 1,  

Mitochondria & Bioenergetics ⓘ

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

Core Metabolism/Glycolysis ⓘ

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

Cell Death ⓘ

Akt↓, 1,   Apoptosis↑, 1,   Casp3↑, 1,   Casp9↑, 1,   cFLIP↓, 1,   DR5↑, 1,   JNK↑, 1,   MAPK↓, 1,   Mcl-1↑, 1,   p27↑, 1,   survivin↓, 1,  

Kinase & Signal Transduction ⓘ

EF-1α↓, 1,   p70S6↓, 1,  

Transcription & Epigenetics ⓘ

cJun↑, 1,   EZH2↓, 1,   H3↑, 1,   H4↑, 1,   HATs↑, 1,  

Protein Folding & ER Stress ⓘ

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

Autophagy & Lysosomes ⓘ

ATG5↑, 1,   LC3II↑, 1,  

DNA Damage & Repair ⓘ

P53↑, 1,   cl‑PARP↑, 1,   PCNA↓, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 3,   CDK4↓, 3,   cycD1/CCND1↓, 3,   cycE/CCNE↓, 1,   P21?, 1,   P21↑, 1,   p‑RB1↓, 1,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

CD133↓, 1,   CSCs↓, 1,   EMT↓, 2,   FOXM1↓, 1,   HDAC↓, 1,   mTOR↓, 1,   p‑mTOR↓, 2,   mTORC1↓, 1,   Nanog↓, 1,   Nestin↓, 1,   NOTCH1↓, 1,   NOTCH3↓, 1,   OCT4↓, 1,   PI3K↓, 2,   RAS↓, 1,   SOX2↓, 1,   STAT3↓, 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,   TumMeta↓, 2,   Twist↓, 1,   Vim↓, 1,   Zeb1↓, 1,   β-catenin/ZEB1↑, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   EGFR↓, 1,   Hif1a↓, 4,   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↓, 1,   ChemoSen↑, 2,   Dose↝, 1,   eff↑, 1,   Half-Life↓, 1,   Half-Life↝, 1,   selectivity↑, 3,  

Clinical Biomarkers ⓘ

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

Functional Outcomes ⓘ

AntiCan↑, 1,   chemoP↑, 2,   neuroP↑, 1,   OS↑, 1,  
Total Targets: 112

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 3,   Catalase↑, 1,   GPx↑, 1,   GSH↑, 1,   Keap1↑, 1,   NRF2↑, 1,   ROS↓, 8,   mt-ROS↓, 1,   SIRT3↑, 6,   SOD↑, 1,   SOD2↑, 1,  

Mitochondria & Bioenergetics ⓘ

mitResp↑, 1,   MMP↑, 3,   PGC-1α↑, 3,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,   PPARγ↑, 4,  

Cell Death ⓘ

p‑Akt↑, 1,   Apoptosis↓, 1,   Casp3↓, 2,  

Transcription & Epigenetics ⓘ

Ach↑, 1,  

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↓, 2,   Rho↓, 1,   β-catenin/ZEB1↑, 1,  

Barriers & Transport ⓘ

BBB↑, 2,  

Immune & Inflammatory Signaling ⓘ

IL1β↓, 2,   Inflam↓, 3,   NF-kB↓, 2,   TNF-α↓, 3,  

Synaptic & Neurotransmission ⓘ

AChE↓, 1,   BDNF↑, 1,   p‑tau↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 3,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   AST↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 3,   cognitive↑, 1,   hepatoP↑, 1,   memory↑, 3,   motorD↑, 2,   neuroP↑, 4,   toxicity↓, 1,  
Total Targets: 48

Scientific Paper Hit Count for: SIRT3, Sirtuin 3
11 Honokiol
2 doxorubicin
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#:934  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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