Honokiol / Hif1a 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

Honokiol — a small, lipophilic biphenolic neolignan isolated principally from the bark, seed cones, and leaves of Magnolia species, especially Magnolia officinalis. It is a natural-product small molecule rather than a standardized Magnolia extract; the standard abbreviation is HNK. Honokiol crosses biological membranes readily and has documented CNS penetration, but its pharmaceutical development is constrained by extremely poor aqueous solubility, rapid metabolism, and low/variable oral systemic exposure. Cancer research is dominated by cell and animal studies, although an oral Phase I window-of-opportunity study in patients with resectable early-stage non-small-cell lung cancer is now enrolling.

Primary mechanisms (ranked):

  1. Mitochondrial targeting and respiratory Complex I inhibition, producing mitochondrial dysfunction, loss of membrane potential, energetic stress, and intrinsic apoptosis in susceptible cancer cells.
  2. Suppression of oncogenic survival signaling, particularly STAT3 and PI3K/AKT/mTOR, with additional inhibition of EGFR and context-dependent MAPK signaling.
  3. Induction of mitochondrial ROS and oxidative stress in cancer cells as a major stress-amplifying mechanism; in nonmalignant tissues honokiol can instead activate antioxidant and mitochondrial-protective programs including SIRT3 and NRF2.
  4. Suppression of NF-κB-dependent inflammatory and prosurvival transcription, contributing to apoptosis, reduced inflammatory signaling, and treatment sensitization.
  5. Suppression of EMT, migration, invasion, cancer-stem-cell phenotypes, and angiogenic signaling through STAT3, Wnt/β-catenin, EGFR, HIF-1α, VEGF, Snail/Slug, MMPs, and related networks.
  6. Metabolic inhibition, including suppression of HIF-1α-driven glycolysis, GLUT1, HK2, LDHA and PDK signaling, with reduced glycolytic flux and ATP availability in several tumor models.
  7. Induction of ER stress, autophagy, cell-cycle arrest and, in selected tumor contexts, ferroptosis; these effects appear downstream or context-dependent rather than universal initiating mechanisms.
  8. Chemosensitization, radiosensitization and immune-modulatory effects have been demonstrated preclinically, including enhancement of selected targeted therapies and PD-1/PD-L1-directed approaches.

Bioavailability / PK relevance: Native honokiol is highly lipophilic and poorly water-soluble, limiting conventional oral and intravenous delivery. It undergoes extensive metabolic clearance, including conjugation, and systemic exposure after ordinary oral formulations may be substantially lower than concentrations commonly used experimentally. Liposomes, nanoemulsions, micelles, nanoparticles and other delivery systems can substantially improve solubility and exposure. A validated pharmacokinetic study of injectable liposomal honokiol has been reported, but clinically established human anticancer PK targets have not yet been defined.

In-vitro vs systemic exposure relevance: Many anticancer studies use approximately 10–60 µM honokiol, with some models requiring still higher concentrations. These concentrations should not automatically be considered achievable following conventional oral supplementation because oral bioavailability is limited and human tumor exposure has not been established. The current Phase I lung-cancer study is therefore important for defining human tolerability, systemic exposure and pharmacodynamic effects rather than demonstrating established therapeutic efficacy.

Clinical evidence status: Predominantly preclinical. Extensive in-vitro and animal anticancer evidence exists across multiple tumor types. Human anticancer efficacy has not been established. A Phase I oral honokiol study in approximately 15 patients with early-stage resectable NSCLC is currently listed by Houston Methodist as enrolling; treatment is given before surgery primarily to determine safety and maximum tolerated dose. Honokiol is not an FDA-approved anticancer drug.

Safety / translation: Preclinical toxicology has generally suggested a comparatively broad therapeutic window, but concentrated honokiol should not be assumed equivalent to historical consumption of Magnolia bark preparations. Potential pharmacokinetic interactions, formulation-dependent exposure, and insufficient controlled human safety data remain major translational limitations. FDA records identify Magnolia cortex extract containing honokiol as having been submitted through the New Dietary Ingredient notification process, but this does not constitute approval of honokiol for cancer treatment.

Honokiol Cancer-Relevant Mechanisms

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 Mitochondrial Complex I and intrinsic apoptosis ↓ Complex I; ↓ ΔΨm; ↓ respiration; ↑ cytochrome-c; ↑ caspases ↔ or mitochondrial protection (context-dependent) P/R Mitochondria-directed cytotoxicity A particularly strong mechanistic feature of honokiol; mitochondrial accumulation and respiratory inhibition can precede downstream apoptotic signaling.
2 STAT3 survival and stemness signaling ↓ STAT3; ↓ p-STAT3; ↓ mitochondrial STAT3 ↔ (context-dependent) R/G Loss of survival, proliferation and stemness signaling Relevant across several cancer models and linked to reduced CSC phenotype, EMT and resistance.
3 PI3K AKT mTOR signaling ↓ PI3K; ↓ AKT; ↓ mTOR ↔ or adaptive modulation R/G Growth and anabolic suppression Frequently observed and contributes to apoptosis, metabolic stress and treatment sensitization.
4 Mitochondrial ROS increase ↑ ROS; ↑ mt-ROS (secondary) ↓ ROS or ↔ (context-dependent) P/R Oxidative stress amplification Cancer-cell ROS elevation often accompanies mitochondrial respiratory disruption. Honokiol can instead act antioxidatively in nonmalignant tissues.
5 NF-κB inflammatory and survival signaling ↓ NF-κB; ↓ COX-2; ↓ inflammatory survival signaling ↓ pathological inflammatory signaling R/G Reduced inflammatory and prosurvival transcription Provides both anticancer and tissue-protective effects depending on cellular context.
6 EMT invasion and metastasis ↓ EMT; ↓ Snail; ↓ Slug; ↓ MMP2; ↓ MMP9; ↑ E-cadherin ↔ G Reduced migration, invasion and metastasis Supported across breast, lung, renal, pancreatic and other tumor models.
7 Cancer stem cell signaling ↓ CSCs; ↓ CD133; ↓ SOX2; ↓ OCT4; ↓ Nestin; ↓ Wnt/β-catenin ↔ G Reduced tumor-initiating and resistant cell phenotype Closely overlaps STAT3, EGFR, Notch and Wnt pathway inhibition.
8 HIF-1α glycolytic metabolism ↓ HIF-1α; ↓ GLUT1; ↓ HK2; ↓ LDHA; ↓ PDK1; ↓ ECAR; ↓ glycolysis ↔ (context-dependent) G Reduced glycolytic flux and ATP production Especially relevant in glycolysis-dependent and hypoxic tumors.
9 EGFR and receptor tyrosine kinase signaling ↓ EGFR; ↓ downstream AKT and ERK ↔ R/G Growth-factor signal suppression Honokiol can also impair EGFR stability through HDAC6/HSP90-associated mechanisms.
10 Angiogenesis and hypoxia response ↓ VEGF; ↓ HIF-1α; ↓ angiogenesis ↔ G Reduced tumor vascular support Largely downstream of HIF-1α, NF-κB and growth-factor suppression.
11 ER stress and calcium signaling ↑ ER stress; ↑ GRP78; ↑ CHOP; ↑ Ca²⁺ (model-dependent) ↔ or protective stress response R/G Proteotoxic stress and apoptosis Prominent in selected osteosarcoma and other experimental models rather than universal across cancers.
12 Cell cycle regulation ↑ G0/G1 or G2/M arrest; ↓ cyclin D1; ↓ CDK2; ↓ CDK4; ↓ CDK6 ↔ G Cytostatic growth suppression Checkpoint phenotype depends on tumor type and upstream signaling context.
13 Ferroptosis and lipid peroxidation ↑ ferroptosis; ↑ lipid peroxidation; GPX4 modulation (model-dependent) ↔ G Alternative regulated cell death GPX4 direction is not uniform across studies; HMOX1-associated and GPX4-associated ferroptosis have both been reported.
14 NRF2 antioxidant response ↔ or ↑ (model-dependent) ↑ NRF2; ↑ antioxidant defenses R/G Secondary tissue-protective redox response NRF2 activation is more compelling as a normal-cell or neuroprotective mechanism than as a core anticancer mechanism.
15 SIRT3 mitochondrial protection ↑ SIRT3 (context-dependent) ↑ SIRT3; ↑ mitochondrial resilience; ↓ oxidative injury R/G Context-dependent mitochondrial regulation Important for cardioprotective and neuroprotective effects; its cancer role can vary with tumor context because SIRT3 itself has context-dependent tumor biology.
16 Chemosensitization and targeted-therapy sensitization ↑ treatment sensitivity (drug-dependent) ↔ or tissue protection G Combination-treatment enhancement Preclinical evidence includes chemotherapy, cetuximab, mTOR inhibitors and immune-checkpoint strategies.
17 Radiosensitization ↑ radiosensitivity (model-dependent) ↔ or radioprotection (context-dependent) G Greater radiation response This apparent duality emphasizes cell type, dose, redox state and treatment timing.
18 Clinical Translation Constraint ↓ achievable exposure with conventional formulations Systemic safety incompletely characterized in humans G Bioavailability and evidence limitation Poor aqueous solubility, extensive metabolism, uncertain human tumor exposure and lack of efficacy trials remain central constraints; Phase I investigation is underway.

P: 0–30 min     R: 30 min–3 hr     G: >3 hr



Honokiol and Alzheimer’s disease: Honokiol has meaningful but entirely preclinical relevance to Alzheimer’s disease and related neurodegeneration. Its lipophilicity permits CNS penetration, and experimental studies indicate reductions in oxidative stress, neuroinflammation, excitotoxicity and Aβ-associated toxicity together with preservation of mitochondrial function. SIRT3, NRF2, PPAR/PGC-1α signaling and restoration of microglial metabolic competence are among the more plausible mechanistic axes. No convincing clinical evidence currently establishes honokiol as an AD treatment.

Evidence level: Preclinical only. Cell and animal studies support neuroprotective and cognition-related effects, but human AD efficacy, dose-response relationships and long-term neurological safety have not been demonstrated.

Honokiol Alzheimer’s-Relevant Mechanisms

Rank Pathway / Axis Modulation Primary Effect Notes / Interpretation
1 Mitochondrial function and SIRT3 ↑ SIRT3; ↑ mitochondrial function; ↑ ΔΨm Mitochondrial resilience One of the strongest mechanistic links between honokiol and neuronal protection.
2 Oxidative stress and NRF2 ↓ ROS; ↑ NRF2; ↑ antioxidant defenses Reduced oxidative injury Direction differs from the pro-oxidant stress frequently induced by honokiol in cancer cells.
3 Microglial metabolism and phagocytosis ↑ PPARα; ↑ PGC-1α; ↑ OXPHOS; ↑ phagocytosis Improved microglial metabolic function Experimental evidence suggests reversal of dysfunctional metabolic programming can restore microglial clearance capacity.
4 Amyloid beta toxicity ↓ Aβ-associated toxicity Neuroprotection Supported primarily by experimental models; evidence for modifying human amyloid pathology is absent.
5 Neuroinflammation ↓ NF-κB; ↓ TNF-α; ↓ IL-1β Reduced inflammatory injury Likely overlaps the general anti-inflammatory pharmacology of honokiol.
6 Excitotoxic calcium signaling ↓ pathological Ca²⁺ signaling Reduced excitotoxic neuronal injury Reported neuroprotective actions include modulation of glutamatergic signaling and intracellular calcium overload.
7 Clinical Translation Constraint No demonstrated human AD efficacy Preclinical evidence only BBB penetration is pharmacologically favorable but does not establish an effective or safe human CNS dose.


Hif1a, HIF1α/HIF1a: Click to Expand ⟱
Source:
Type:
Hypoxia-Inducible-Factor 1A (HIF1A gene, HIF1α, HIF-1α protein product)
-Dominantly expressed under hypoxia(low oxygen levels) in solid tumor cells
-HIF1A induces the expression of vascular endothelial growth factor (VEGF)
-High HIF-1α expression is associated with Poor prognosis
-Low HIF-1α expression is associated with Better prognosis

-Functionally, HIF-1α is reported to regulate glycolysis, whilst HIF-2α regulates genes associated with lipoprotein metabolism.
-Cancer cells produce HIF in response to hypoxia in order to generate more VEGF that promote angiogenesis

Key mediators of aerobic glycolysis regulated by HIF-1α.
-GLUT-1 → regulation of the flux of glucose into cells.
-HK2 → catalysis of the first step of glucose metabolism.
-PKM2 → regulation of rate-limiting step of glycolysis.
-Phosphorylation of PDH complex by PDK → blockage of OXPHOS and promotion of aerobic glycolysis.
-LDH (LDHA): Rapid ATP production, conversion of pyruvate to lactate;

HIF-1α Inhibitors:
-Curcumin: disruption of signaling pathways that stabilize HIF-1α (ie downregulate).
-Resveratrol: downregulate HIF-1α protein accumulation under hypoxic conditions.
-EGCG: modulation of upstream signaling pathways, leading to decreased HIF-1α activity.
-Emodin: reduce HIF-1α expression. (under hypoxia).
-Apigenin: inhibit HIF-1α accumulation.
Scientific Papers found: Click to Expand⟱
2896- HNK,    Honokiol inhibits hypoxia-inducible factor-1 pathway
- in-vivo, Colon, CT26
Hif1a↓, Our data suggest that honokiol can exert its anticancer activity as a HIF-1α inhibitor by reducing HIF-1α protein level and suppressing the hypoxia-related signaling pathway.
RadioS↑, The animal experiment indicates that honokiol improves the therapeutic efficacy of radiation

2900- HNK,    The Role and Therapeutic Perspectives of Sirtuin 3 in Cancer Metabolism Reprogramming, Metastasis, and Chemoresistance
- Review, Var, NA
SIRT3↑, Honokiol blocks the growth of lung cancer cells by activating SIRT3 to inhibit HIF-1α expression
Hif1a↓,
ChemoSen↑, and also be used as adjuvant chemotherapy to prevent doxorubicin-induced cardiotoxicity in tumors transplanted mice
chemoP↑,

2894- HNK,    Pharmacological features, health benefits and clinical implications of honokiol
- Review, Var, NA - Review, AD, NA
*BioAv↓, HNK showed poor aqueous solubility due to phenolic hydroxyl groups forming intramolecular hydrogen bonds and poor solubility in water (
*neuroP↑, HNK has the accessibility to reach the neuronal tissue by crossing the BBB and showing neuroprotective effects
*BBB↑,
*ROS↓, fig 2
*Keap1↑,
*NRF2↑,
*Casp3↓,
*SIRT3↑,
*Rho↓,
*ERK↓,
*NF-kB↓,
angioG↓,
RAS↓,
PI3K↓,
Akt↓,
mTOR↓,
*memory↑, oral administration of HNK (1 mg/kg) in senescence-accelerated mice prevents age-related memory and learning deficits
*Aβ↓, in Alzheimer’s disease, HNK significantly reduces neurotoxicity of aggregated Ab
*PPARγ↑, Furthermore, the expression of PPARc and PGC1a was increased by HNK, suggesting its beneficial impact on energy metabolism
*PGC-1α↑,
NF-kB↓, activation of NFjB was suppressed by HNK via suppression of nuclear translocation and phosphorylation of the p65 subunit and further instigated apoptosis by enhancing TNF-a
Hif1a↓, HNK has anti-oxidative properties and can downregulate the HIF-1a protein, inhibiting hypoxia- related signaling pathways
VEGF↓, renal cancer, via decreasing the vascular endothelial growth factor (VEGF) and heme-oxygenase-1 (HO-1)
HO-1↓,
FOXM1↓, HNK interaction with the FOXM1 oncogenic transcription factor inhibits cancer cells
p27/CDKN1B↑, HNK treatment upregulates the expression of CDK inhibitor p27 and p21, whereas it downregulates the expression of CDK2/4/6 and cyclin D1/2
P21↑,
CDK2↓,
CDK4↓,
CDK6↓,
cycD1/CCND1↓,
Twist↓, HNK averted the invasion of urinary bladder cancer cells by downregulating the steroid receptor coactivator, Twist1 and Matrix metalloproteinase-2
MMP2↓,
Rho↑, By activating the RhoA, ROCK and MLC signaling, HNK inhibits the migration of highly metastatic renal cell carcinoma
ROCK1↑,
TumCMig↓,
cFLIP↓, HNK can be used to suppress c-FLIP, the apoptosis inhibitor.
BMPs↑, HNK treatment increases the expression of BMP7 protein
OCR↑, HNK might increase the oxygen consumption rate while decreasing the extracellular acidification rate in breast cancer cells.
ECAR↓,
*AntiAg↑, It also suppresses the platelet aggregation
*cardioP↑, HNK is an attractive cardioprotective agent because of its strong antioxidative properties
*antiOx↑,
*ROS↓, HNK treatment reduced cellular ROS production and decreased mitochondrial damage in neonatal rat cardiomyocytes exposed to hypoxia/reoxygenation
P-gp/ABCB1↓, The expres- sion of P-gp at mRNA and protein levels is reduced in HNK treatment on human MDR and MCF-7/ADR breast cancer cell lines

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↑, Honokiol was shown to induce G1 arrest and apoptosis to inhibit the growth of KRAS mutant lung cancer cells
Apoptosis↑,
SIRT3↑, we also discovered that Sirt3 was significantly up-regulated in honokiol treated KRAS mutant lung cancer cells,
Hif1a↓, leading to destabilization of its target gene Hif-1α, (accompanied by a reduction of Hif-1a expression)
selectivity↑, but it showed low toxicity to two normal lung cells (CCD19-Lu and BEAS-2B)
p‑mTOR↓, honokiol suppressed mTOR phosphorylation, leading to inhibition of P70S6K kinase activity,
p70S6↓,

960- HNK,    Honokiol Inhibits HIF-1α-Mediated Glycolysis to Halt Breast Cancer Growth
- vitro+vivo, BC, MCF7 - vitro+vivo, BC, MDA-MB-231
OCR↑, which resulted in an increase in OCR and a decrease in ECAR, glucose uptake, lactic acid production and ATP production.
ECAR↓,
GlucoseCon↓, decreased glucose uptake, lactate production and ATP production in cancer cells.
lactateProd↓,
ATP↓,
Glycolysis↓,
Hif1a↓,
GLUT1↓,
HK2↓,
PDK1 / PDPK1↓,
Apoptosis↑,
LDHA↓, upregulation of LDHA mediated by HIF-1α promoted the formation of lactic acid from pyruvate, which contributed to the acidification of the tumor microenvironment. Our experimental observation results showed that these changes were reversed by HNK

2864- HNK,    Honokiol: A Review of Its Anticancer Potential and Mechanisms
- Review, Var, NA
TumCCA↑, induction of G0/G1 and G2/M cell cycle arrest
CDK2↓, (via the regulation of cyclin-dependent kinase (CDK) and cyclin proteins),
EMT↓, epithelial–mesenchymal transition inhibition via the downregulation of mesenchymal markers
MMPs↓, honokiol possesses the capability to supress cell migration and invasion via the downregulation of several matrix-metalloproteinases
AMPK↑, (activation of 5′ AMP-activated protein kinase (AMPK) and KISS1/KISS1R signalling)
TumCI↓, inhibiting cell migration, invasion, and metastasis, as well as inducing anti-angiogenesis activity (via the down-regulation of vascular endothelial growth factor (VEGFR) and vascular endothelial growth factor (VEGF)
TumCMig↓,
TumMeta↓,
VEGFR2/KDR/Flk1↓,
*antiOx↑, diverse biological activities, including anti-arrhythmic, anti-inflammatory, anti-oxidative, anti-depressant, anti-thrombocytic, and anxiolytic activities
*Inflam↓,
*BBB↑, Due to its ability to cross the blood–brain barrier
*neuroP↑, beneficial towards neuronal protection through various mechanism, such as the preservation of Na+/K+ ATPase, phosphorylation of pro-survival factors, preservation of mitochondria, prevention of glucose, reactive oxgen species (ROS), and inflammatory
*ROS↓,
Dose↝, Generally, the concentrations used for the in vitro studies are between 0–150 μM
selectivity↑, Interestingly, honokiol has been shown to exhibit minimal cytotoxicity against on normal cell lines, including human fibroblast FB-1, FB-2, Hs68, and NIH-3T3 cells
Casp3↑, ↑ Caspase-3 & caspase-9
Casp9↑,
NOTCH1↓, Inhibition of Notch signalling: ↓ Notch1 & Jagged-1;
cycD1/CCND1↓, ↓ cyclin D1 & c-Myc;
cMyc↓,
P21?, ↑ p21WAF1 protein
DR5↑, ↑ DR5 & cleaved PARP
cl‑PARP↑,
P53↑, ↑ phosphorylated p53 & p53
Mcl-1↑, ↓ Mcl-1 protein
p65↓, ↓ p65; ↓ NF-κB
NF-kB↓,
ROS↑, ↑ JNK activation ,Increase ROS activity:
JNK↑,
NRF2↑, ↑ Nrf2 & c-Jun protein activation
cJun↑,
EF-1α↓, ↓ EFGR; ↓ MAPK/PI3K pathway activity
MAPK↓,
PI3K↓,
mTORC1↓, ↓ mTORC1 function; ↑ LKB1 & cytosolic localisation
CSCs↓, Inhibit stem-like characteristics: ↓ Oct4, Nanog & Sox4 protein; ↓ STAT3;
OCT4↓,
Nanog↓,
SOX4↓,
STAT3↓,
CDK4↓, ↓ Cdk2, Cdk4 & p-pRbSer780;
p‑RB1↓,
PGE2↓, ↓ PGE2 production ↓ COX-2 ↑ β-catenin
COX2/PTGS2↓,
β-catenin/ZEB1↑,
IKKα↓, ↓ IKKα
HDAC↓, ↓ class I HDAC proteins; ↓ HDAC activity;
HATs↑, ↑ histone acetyltransferase (HAT) activity; ↑ histone H3 & H4
H3↑,
H4↑,
LC3II↑, ↑ LC3-II
c-Raf↓, ↓ c-RAF
SIRT3↑, ↑ Sirt3 mRNA & protein; ↓ Hif-1α protein
Hif1a↓,
ER Stress↑, ↑ ER stress signalling pathway activation; ↑ GRP78,
GRP78/BiP↑,
cl‑CHOP/DDIT3↑, ↑ cleaved caspase-9 & CHOP;
MMP↓, mitochondrial depolarization
PCNA↓, ↓ cyclin B1, cyclin D1, cyclin D2 & PCNA;
Zeb1↓, ↓ ZEB2 Inhibit
NOTCH3↓, ↓ Notch3/Hes1 pathway
CD133↓, ↓ CD133 & Nestin protein
Nestin↓,
ATG5↑, ↑ Atg7 protein activation; ↑ Atg5;
ATG7↑,
survivin↓, ↓ Mcl-1 & survivin protein
ChemoSen↑, honokiol potentiated the apoptotic effect of both doxorubicin and paclitaxel against human liver cancer HepG2 cells.
SOX2↓, Honokiol was shown to downregulate the expression of Oct4, Nanog, and Sox2 which were known to be expressed in osteosarcoma, breast carcinoma and germ cell tumours
OS↑, Lipo-HNK was also shown to prolong survival and induce intra-tumoral apoptosis in vivo.
P-gp/ABCB1↓, Honokiol was shown to downregulate the expression of P-gp at mRNA and protein levels in MCF-7/ADR, a human breast MDR cancer cell line
Half-Life↓, For i.v. administration, it has been found that there was a rapid rate of distribution followed by a slower rate of elimination (elimination half-life t1/2 = 49.22 min and 56.2 min for 5 mg or 10 mg of honokiol, respectively
Half-Life↝, male and female dogs was assessed. The elimination half-life (t1/2 in hours) was found to be 20.13 (female), 9.27 (female), 7.06 (male), 4.70 (male), and 1.89 (male) after administration of doses of 8.8, 19.8, 3.9, 44.4, and 66.7 mg/kg, respectively.
eff↑, Apart from that, epigallocatechin-3-gallate functionalized chitin loaded with honokiol nanoparticles (CE-HK NP), developed by Tang et al. [224], inhibit HepG2
BioAv↓, extensive biotransformation of honokiol may contribute to its low bioavailability.

2082- HNK,    Revealing the role of honokiol in human glioma cells by RNA-seq analysis
- in-vitro, GBM, U87MG - in-vitro, GBM, U251
AntiCan↑, In summary, studies have demonstrated that honokiol has multiple anticancer effects
TumCP↑, honokiol suppresses cell proliferation, and promotes autophagy and apoptosis
TumAuto↑,
Apoptosis↑,
*BioAv↑, honokiol could improve bioavailability in nerve tissue through passing the blood-brain barrie
*neuroP↑, honokiol has neuroprotective effects.
*NF-kB↑, honokiol could reduce cytokine production and stimulate glial nuclear factor kappa B (NFκB) to eliminate the inflammatory response during cerebral ischemia-reperfusion activity
MAPK↑, honokiol activated cells MAPK signaling pathway in human glioma cells
GPx4↑, The results showed that the ferroptosis-associated protein GPX4 was suppressed in honokiol-treated cells compared to control cells.
Tf↑, Ferroptosis-associated protein TF was upregulated in both honokiol-treated cell lines compared to the control
BAX↑, BAX was increased, and the expression of Bcl-2 was suppressed in both honokiol-treated cells, indicating that honokiol induced apoptosis in the human glioma cell lines U87-MG and U251-MG.
Bcl-2↓,
antiOx↑, Researchers have found that the antioxidant capacity of honokiol is 1000 times greater than that of vitamin E
Hif1a↓, reduce HIF-1α protein levels and suppress hypoxia-related signaling pathways
Ferroptosis↑, Honokiol activated ferroptosis in human glioma cells


Showing Research Papers: 1 to 7 of 7

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 7

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1,   Ferroptosis↑, 1,   GPx4↑, 1,   HO-1↓, 1,   NRF2↑, 1,   ROS↑, 1,   SIRT3↑, 3,  

Metal & Cofactor Biology(tgid=2) ⓘ

Tf↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

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

Core Metabolism/Glycolysis(tgid=4) ⓘ

AMPK↑, 1,   ATG7↑, 1,   cMyc↓, 1,   ECAR↓, 2,   GlucoseCon↓, 1,   Glycolysis↓, 1,   HK2↓, 1,   lactateProd↓, 1,   LDHA↓, 1,   PDK1 / PDPK1↓, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 1,   Apoptosis↑, 3,   BAX↑, 1,   Bcl-2↓, 1,   Casp3↑, 1,   Casp9↑, 1,   cFLIP↓, 1,   DR5↑, 1,   Ferroptosis↑, 1,   JNK↑, 1,   MAPK↓, 1,   MAPK↑, 1,   Mcl-1↑, 1,   p27/CDKN1B↑, 1,   survivin↓, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

EF-1α↓, 1,   p70S6↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

cJun↑, 1,   H3↑, 1,   H4↑, 1,   HATs↑, 1,  

Protein Folding & ER Stress(tgid=8) ⓘ

cl‑CHOP/DDIT3↑, 1,   ER Stress↑, 1,   GRP78/BiP↑, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

ATG5↑, 1,   LC3II↑, 1,   TumAuto↑, 1,  

DNA Damage & Repair(tgid=10) ⓘ

P53↑, 1,   cl‑PARP↑, 1,   PCNA↓, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

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

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

CD133↓, 1,   CSCs↓, 1,   EMT↓, 1,   FOXM1↓, 1,   HDAC↓, 1,   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,  

Migration(tgid=13) ⓘ

MMP2↓, 1,   MMPs↓, 1,   Rho↑, 1,   ROCK1↑, 1,   SOX4↓, 1,   TumCI↓, 1,   TumCMig↓, 2,   TumCP↑, 1,   TumMeta↓, 1,   Twist↓, 1,   Zeb1↓, 1,   β-catenin/ZEB1↑, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 1,   Hif1a↓, 7,   VEGF↓, 1,   VEGFR2/KDR/Flk1↓, 1,  

Barriers & Transport(tgid=15) ⓘ

GLUT1↓, 1,   P-gp/ABCB1↓, 2,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 1,   IKKα↓, 1,   NF-kB↓, 2,   p65↓, 1,   PGE2↓, 1,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

CDK6↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

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

Clinical Biomarkers(tgid=22) ⓘ

BMPs↑, 1,   FOXM1↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1,   chemoP↑, 1,   OS↑, 1,  
Total Targets: 113

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 2,   Keap1↑, 1,   NRF2↑, 1,   ROS↓, 3,   SIRT3↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

PGC-1α↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

PPARγ↑, 1,  

Cell Death(tgid=5) ⓘ

Casp3↓, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

ERK↓, 1,  

Migration(tgid=13) ⓘ

AntiAg↑, 1,   Rho↓, 1,  

Barriers & Transport(tgid=15) ⓘ

BBB↑, 2,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

Inflam↓, 1,   NF-kB↓, 1,   NF-kB↑, 1,  

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 1,   BioAv↑, 1,  

Functional Outcomes(tgid=23) ⓘ

cardioP↑, 1,   memory↑, 1,   neuroP↑, 3,  
Total Targets: 21

Scientific Paper Hit Count for: Hif1a, HIF1α/HIF1a
7 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#:143  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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