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

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.


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⟱
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↓, Honokiol suppressed cell proliferation via increasing cell apoptosis, invasion, and migration with dose dependence.
Apoptosis↑,
TumCI↓,
TumCMig↓,
HER2/EBBR2↓, HER2 protein expression was significantly depressed in honokiol-treated groups
TumCCA↑, results show that Hon kept the cell cycle in G1 phase, which might be the cause of the cell apoptosis rate increase.
PI3K↓, PI3K, AKT, and MMP-9 protein and mRNA expression of Hon-treated groups were significantly suppressed
Akt↓,
MMP9↓,
P21↑, increase P21 protein and gene expression

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↓,

7468- HNK,    Honokiol and Its Emerging Role in Breast Cancer Therapy
- Review, BC, NA
*ROS↓, HNK inhibits essential oncogenic pathways and reduces oxidative stress, inflammation, metabolic reprogramming, and cancer stemness.
*Inflam↓,
CSCs↓,
ChemoSen↑, HNK demonstrates synergistic activity with chemotherapy, endocrine therapy, targeted therapy, and immune checkpoint inhibitors, increasing sensitivity to treatment across models of ER+, PR+, and HER2+ BrCas, as well as triple-negative breast cancers
BioAv↑, Nanotechnological delivery systems enhance the solubility, bioavailability, and intratumoral accumulation of HNK, increasing its translational capacity.
ROS↑, HNK increases intracellular reactive oxygen species (ROS) levels in cancer cells, coinciding with a time-dependent loss of mitochondrial membrane potential (ΔΨm), indicating that ROS production is closely linked to mitochondrial damage
MMP↓,
mtDam↑,
TumCCA↑, HNK causes G0/G1 cell cycle arrest by downregulating cyclin D1 and CDK4, as well as promoting intrinsic apoptosis-like pathways marked by increases in caspase-3 and caspase-9 activities
cycD1/CCND1↓,
CDK4↓,
Casp3↑,
Casp9↑,
Bcl-2↓, reducing the anti-apoptotic Bcl-2 and Bcl-xL, and increasing the pro-apoptotic Bax
Bcl-xL↓,
BAX↑,
p‑STAT3↓, HNK suppresses the phosphorylation of STAT3 in MDA-MB-231
AMPK↑, HNK was found to activate the LKB1–AMPK axis and induce miR-34a expression in MCF7, SKBR3, and SUM149 cells, thereby inhibiting EMT, stemness, and oncogenic leptin signaling in an LKB1-dependent manner
miR-34a↑,
EMT↓,
HH↓, HNK can induce apoptosis by suppressing essential components of the Hh pathway, including SHH [28], Gli1, and Ptch1 [26], as well as downregulating NF-κB
Shh↓,
Gli1↓,
PTCH1↓,
NF-kB↓,
TNF-α↓, reduces the production of inflammatory cytokines, including TNF-α and IL-6
IL6↓,
Glycolysis↓, HNK suppresses HIF-1α-controlled glycolysis by downregulating glycolytic metabolic enzymes, disrupting glucose uptake, and inhibiting tumor growth.
GlucoseCon↓,
BioAv↓, This limitation is primarily attributed to pharmacokinetic challenges, including poor aqueous solubility, low oral bioavailability, rapid metabolism, and the lack of standardized dosing regimens,
BioAv↓, Preclinical studies demonstrate that following oral administration at 40 mg/kg, HNK is rapidly absorbed (Tmax ≈ 20 min) but exhibits low systemic exposure [75], due to extensive first-pass metabolism and high hepatic extraction
Half-Life↝, While the plasma elimination half-life is moderately prolonged (t½ ≈ 290 min),

7463- HNK,    Honokiol Inhibits Colorectal Cancer Cell Growth: Involvement of Hsp27 as a Molecular Target
- in-vitro, CRC, NA
TumCG↓, HK dose-dependently suppressed anchorage-independent growth of CRC cells and induced G0/G1 arrest.
TumCCA↑,
Cyt‑c↑, It triggered apoptosis through cytochrome c release, PARP cleavage, and Bcl-2 downregulation.
Apoptosis↑,
cl‑PARP↑,
Bcl-2↓,
HSP27↓, HK exerts anti-cancer effects in CRC cells, associated with Hsp27 inhibition,

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↑, honokiol (H), magnolol (M), and baicalin (B) are found to exhibit a synergistic anticancer effect on CRC
eff↑, Most importantly, HMB is shown to enhance the sensitivity of CRC cells to anti‐PD‐1 immunotherapy in vivo.
TumCP↓, HMB Synergistically Inhibits Cell Proliferation and Triggers Cell Death in CRC Cells and Organoid Models
TumCCA↓, HMB treatment induced G0/G1 phase arrest, accompanied by reduced expression of cyclin D1 and p‐RB expression in both HCT116 and LoVo cells.
cycD1/CCND1↓,
Pyro↑, HMB Synergistically Induces Pyroptosis and Apoptosis
Apoptosis↑,
cl‑GSDME↑, HMB Synergistically Induces Pyroptosis by Promoting the Cleavage of GSDME
Bcl-2↓, HMB treatment reduced Bcl‐2 expression, promoted cytochrome c release from mitochondria, and activated caspase‐9
Cyt‑c↑,
Casp9↑,
TumCG↓, results demonstrate that the HMB combination synergistically inhibited tumor growth and induced pyroptosis in vivo

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.

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↓, honokiol decreased the viability of the targeted AML cells
TumCCA↑, induced their cell cycle arrest at G0/G1 phase
Ferroptosis↑, Honokiol also triggers a noncanonical ferroptosis pathway in THP-1 and U-937 cells by upregulating the level of intracellular lipid peroxide and HMOX1 significantly.
lipid-P↑,
HO-1↑, HMOX1
GPx4∅, Honokiol elevated the expression of HMOX1 but did not inhibit the expression of GPX4

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↑, honokiol caused dose-dependent and time-dependent cell death in human osteosarcoma cells
TumAuto↑, death induced by honokiol were primarily autophagy and apoptosis.
Apoptosis↑,
TumCCA↑, honokiol induced G0/G1 phase arrest,
GRP78/BiP↑, elevated the levels of glucose-regulated protein (GRP)−78, an endoplasmic reticular stress (ERS)-associated protein
ROS↑, increased the production of intracellular reactive oxygen species (ROS)
eff↓, In contrast, reducing production of intracellular ROS using N-acetylcysteine, a scavenger of ROS, concurrently suppressed honokiol-induced cellular apoptosis, autophagy, and cell cycle arrest.
p‑ERK↑, honokiol stimulated phosphorylation of extracellular signal-regulated kinase (ERK)1/2.
selectivity↑, human fibroblasts showed strong resistance to HNK, the IC50 values for which were 118.9 and 71.5 μM
Ca+2↑, HNK increased intracellular Ca2+ in both HOS and U2OS cells
MMP↓, mitochondrial membrane potential (MMP) sharply decreased following HNK treatment
Casp3↑, HNK markedly activated caspase-3, caspase-9
Casp9↑,
cl‑PARP↑, led to PARP cleavage
Bcl-2↓, expression of Bcl-2, Bcl-xl, and survivin was found to be decreased
Bcl-xL↓,
survivin↓,
LC3B-II↑, HNK increased the level of LC3B-II and Atg5 in HOS and U2OS cells.
ATG5↑,
TumVol↓, HNK at doses of 40 mg/kg resulted in significant decrease in tumor volume and weight, after 7 days of drug administration
TumW↓,
ER Stress↑, ER stress can trigger ROS production through release of calcium

1004- HNK,  RAPA,    Honokiol downregulates PD-L1 expression and enhances antitumor effects of mTOR inhibitors in renal cancer cells
- in-vitro, RCC, NA
Apoptosis↑, HNK is more potent than RAPA, both HNK and RAPA inhibited the proliferation of renal cancer cells and promoted apoptosis
TumCCA↑, G1 phase cell cycle arrest
ROS↑, HNK and RAPA significantly increased ROS generation in these cells and it was much higher in the HNK and RAPA combinatorial treatment.
PD-L1↓, HNK, but not RAPA, significantly decreased the expression of PD-L1
IFN-γ↓, HNK can also downmodulate IFN-γ-induced PD-L1expression

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↓, Treatment of NSCLC cells (A549, H1299, H460 and H226) with honokiol (20, 40 and 60 µM) inhibited histone deacetylase (HDAC) activity, reduced the levels of class I HDAC proteins and enhanced histone acetyltransferase activity in a dose-dependent man
tumCV↓, These effects of honokiol were associated with a significant reduction in the viability of NSCLC cells
TumCCA↑, Treatment of A549 and H1299 cells with honokiol resulted in an increase in G1 phase arrest, and a decrease in the levels of cyclin D1, D2 and cyclin dependent kinases.
cycD1/CCND1↓,
ac‑H3↑, Honokiol increases the levels of acetylated histone H3 and H4 in NSCLC cells
ac‑H4↑,
selectivity↑, Honokiol inhibits cell growth or viability of human NSCLC cells but not normal human bronchial epithelial cells
CDK2↓, Similarly, a marked reduction in the expression of CDK2, CDK4 and CDK6 proteins was observed
CDK4↓,

2881- HNK,    Honokiol Suppressed Pancreatic Cancer Progression via miR-101/Mcl-1 Axis
- in-vitro, PC, PANC1
tumCV↓, Honokiol concentration-dependently suppressed pancreatic cancer cell viability.
Casp3↑, honokiol increased the caspase-3 activity and cell apoptotic rates, induced cell cycle arrest at G0/G1 phase, and inhibited cell invasion in pancreatic cancer.
Apoptosis↑,
TumCCA↑,
TumCI↓,
Mcl-1↓, up-regulated miR-101 expression but down-regulated Mcl-1 expression in tumor tissues.
EMT↓, Recent studies reported honokiol inhibits cancer metastasis by blocking EMT through modulation of Snail/Slug protein translation

2879- HNK,    Honokiol Inhibits Lung Tumorigenesis through Inhibition of Mitochondrial Function
- in-vitro, Lung, H226 - in-vivo, NA, NA
tumCV↓, honokiol significantly reduced the percentage of bronchial that exhibit abnormal lung SCC histology from 24.4% bronchial in control to 11.0% bronchial in honokiol treated group (p= 0.01) while protecting normal bronchial histology (present in 20.5%
selectivity↑,
TumCP↓, In vitro studies revealed that honokiol inhibited lung SCC cells proliferation, arrested cells at the G1/S cell cycle checkpoint, while also leading to increased apoptosis.
TumCCA↑,
Apoptosis↑,
mt-ROS↑, interfering with mitochondrial respiration is a novel mechanism by which honokiol increased generation of reactive oxygen species (ROS) in the mitochondria, : mitochondrial ROS generation
Casp3↑, cells treated with honokiol showed a significant increase in caspase 3/7 activity, which occurred in dose- and time-dependent manners
Casp7↑,
OCR↓, Honokiol caused a fast and concentration-dependent decrease in basal oxygen consumption rate (OCR) in both cell lines
Cyt‑c↑, cytochrome c release was increased in honokil treated mouse lung SCC tissue
ATP↓, found a dramatic decrease in cellular ATP content
mitResp↓, Honokiol inhibits mitochondrial respiration and decreases ATP levels in H226 and H520 cells, which may elevate AMP and the intracellular AMP/ATP ratio, leading to activation of the AMPK
AMP↑,
AMPK↑,


Showing Research Papers: 1 to 12 of 12

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 12

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

Ferroptosis↑, 1,   GPx4∅, 1,   HO-1↑, 1,   lipid-P↑, 1,   NRF2↑, 1,   ROS↑, 4,   mt-ROS↑, 1,   SIRT3↑, 2,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↓, 1,   mitResp↓, 1,   MMP↓, 3,   mtDam↑, 1,   OCR↓, 1,   c-Raf↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

AMP↑, 1,   AMPK↑, 3,   ATG7↑, 1,   cMyc↓, 1,   GlucoseCon↓, 1,   Glycolysis↓, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 1,   Apoptosis↑, 8,   BAX↑, 1,   Bcl-2↓, 4,   Bcl-xL↓, 2,   Casp3↑, 5,   Casp7↑, 1,   Casp9↑, 4,   Cyt‑c↑, 3,   DR5↑, 1,   Ferroptosis↑, 1,   cl‑GSDME↑, 1,   JNK↑, 1,   MAPK↓, 1,   Mcl-1↓, 1,   Mcl-1↑, 1,   Pyro↑, 1,   survivin↓, 2,   TumCD↑, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

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

Transcription & Epigenetics(tgid=7) ⓘ

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

Protein Folding & ER Stress(tgid=8) ⓘ

cl‑CHOP/DDIT3↑, 1,   ER Stress↑, 2,   GRP78/BiP↑, 2,   HSP27↓, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

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

DNA Damage & Repair(tgid=10) ⓘ

P53↑, 1,   cl‑PARP↑, 3,   PCNA↓, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

CDK2↓, 2,   CDK4↓, 3,   cycD1/CCND1↓, 4,   P21?, 1,   P21↑, 1,   p‑RB1↓, 1,   TumCCA↓, 1,   TumCCA↑, 11,  

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

CD133↓, 1,   CSCs↓, 2,   EMT↓, 3,   p‑ERK↑, 1,   Gli1↓, 1,   HDAC↓, 2,   HH↓, 1,   miR-34a↑, 1,   p‑mTOR↓, 1,   mTORC1↓, 1,   Nanog↓, 1,   Nestin↓, 1,   NOTCH1↓, 1,   NOTCH3↓, 1,   OCT4↓, 1,   PI3K↓, 2,   PTCH1↓, 1,   Shh↓, 1,   SOX2↓, 1,   STAT3↓, 1,   p‑STAT3↓, 1,   TumCG↓, 2,  

Migration(tgid=13) ⓘ

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

Angiogenesis & Vasculature(tgid=14) ⓘ

Hif1a↓, 2,   VEGFR2/KDR/Flk1↓, 1,  

Barriers & Transport(tgid=15) ⓘ

P-gp/ABCB1↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 1,   IFN-γ↓, 1,   IKKα↓, 1,   IL6↓, 1,   NF-kB↓, 2,   p65↓, 1,   PD-L1↓, 1,   PGE2↓, 1,   TNF-α↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 3,   BioAv↑, 1,   ChemoSen↑, 2,   Dose↝, 1,   eff↓, 1,   eff↑, 2,   Half-Life↓, 1,   Half-Life↝, 2,   selectivity↑, 5,  

Clinical Biomarkers(tgid=22) ⓘ

HER2/EBBR2↓, 1,   IL6↓, 1,   PD-L1↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1,   OS↑, 1,   TumVol↓, 1,   TumW↓, 1,  
Total Targets: 128

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1,   ROS↓, 2,  

Barriers & Transport(tgid=15) ⓘ

BBB↑, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

Inflam↓, 2,  

Functional Outcomes(tgid=23) ⓘ

neuroP↑, 1,  
Total Targets: 5

Scientific Paper Hit Count for: TumCCA, Tumor cell cycle arrest
12 Honokiol
1 Magnolol
1 Baicalin
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#:%
  wNotes=on  sortOrder:rid,rpid

 

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