condition found tbRes List
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


EMT, Epithelial-Mesenchymal Transition: Click to Expand ⟱
Source:
Type:
Biological process in which epithelial cells lose their cell polarity and cell-cell adhesion properties and gain mesenchymal traits, such as increased motility and invasiveness. This process is pivotal during embryogenesis and wound healing. Hh signaling pathway is able to regulate the EMT. Snail, E-cadherin and N-cadherin, key components of EMT; EMT-related factors, E-cadherin, N-cadherin, vimentin; The hallmark of EMT is the upregulation of N-cadherin followed by the downregulation of E-cadherin.
EMT is regulated by various signaling pathways, including TGF-β, Wnt, Notch, and Hedgehog pathways. Transcription factors such as Snail, Slug, Twist, and ZEB play critical roles in repressing epithelial markers (like E-cadherin) and promoting mesenchymal markers (like N-cadherin and vimentin).
EMT is associated with increased tumor aggressiveness, enhanced migratory and invasive capabilities, and resistance to apoptosis.
Scientific Papers found: Click to Expand⟱
2877- HNK,    Targeting histone deacetylase-3 blocked epithelial-mesenchymal plasticity and metastatic dissemination in gastric cancer
- in-vitro, GC, AGS
HDAC3↓, Honokiol significantly abolished HDAC3 activity (Y298) via inhibition of NFκBp65/CEBPβ signaling,
NF-kB↓,
CEBPB↓,
ER Stress↑, Honokiol increased ER stress markers and inhibited EMT-associated epithelial markers, but decreased Wnt/β-catenin activity
EMT↓,
Wnt↓,
β-catenin/ZEB1↓,

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

2882- HNK,    Honokiol Suppresses Perineural Invasion of Pancreatic Cancer by Inhibiting SMAD2/3 Signaling
- in-vitro, PC, PANC1
TumCI↓, HNK can inhibit the invasion and migration of pancreatic cancer cells.
TumCMig↓,
p‑SMAD2↓, partially mediated by inhibition of SMAD2/3 phosphorylation.
p‑SMAD3↓,
EMT↓, HNK Inhibits Pancreatic Cancer Malignant Behaviors and EMT
N-cadherin↓, expression of N-cadherin and Vimentin was gradually downregulated, while HNK promoted the expression of E-cadherin in PANC-1
Vim↓,
E-cadherin↑,
Snail↓, HNK can inhibit breast cancer cell metastasis by blocking EMT through downregulating Snail/Slug protein translation
Slug↓,
Rho↓, Honokiol inhibits the migration of renal cell carcinoma through activation of the RhoA/ROCK/MLC signaling pathway
ROCK1↓,

2883- HNK,    Honokiol targets mitochondria to halt cancer progression and metastasis
- Review, Var, NA
ChemoSen↑, Combination of HNK with many traditional chemotherapeutic drugs as well as radiation sensitizes cancer cells to apoptotic death
BBB↓, HNK is also capable of crossing the BBB
Ca+2↑, HNK promotes human glioblastoma cancer cell apoptosis via regulation of Ca(2+) channels
Cyt‑c↑, release of mitochondrial cytochrome c and activation of caspase-3
Casp3↑,
chemoP↑, potent chemopreventive agent against lung SCC development in a carcinogen-induced lung SCC murine model
OCR↓, HNK treatment results in a decreased oxygen consumption rate (OCR) in whole intact cells, rapidly, and persistently inhibiting mitochondrial respiration, which leads to the induction of apoptosis
mitResp↓,
Apoptosis↑,
RadioS↑, Honokiol as a chemo- and radiosensitizer
NF-kB↓, HNK as an anticancer drug is its potential to inhibit multiple important survival pathways, such as NF-B and Akt
Akt↓,
TNF-α↓, by inhibiting TNF-induced nerve growth factor IB expression in breast cancer cells
PGE2↓, reduced prostaglandin E2 (PGE2) and vascular endothelial growth factor (VEGF) secretion levels
VEGF↓,
NO↝, HNK inhibits cancer cell migration by targeting nitric oxide and cyclooxygenase-2 or Ras GTPase-activating-like protein (IQGAP1) [
COX2↓,
RAS↓,
EMT↓, HNK can reverse the epithelial-mesenchymal-transition (EMT) process, which is a key step during embryogenesis, cancer invasion, and metastasis,
Snail↓, HNK reduced the expression levels of Snail, N-cadherin and -catenin, which are mesenchymal markers, but increased E-cadherin,
N-cadherin↓,
β-catenin/ZEB1↓,
E-cadherin↑,
ER Stress↑, induction of ER stress
p‑STAT3↓, HNK inhibited STAT3 phosphorylation
EGFR↓, inhibiting EGFR phosphorylation and its downstream signaling pathways such as the mTOR signaling pathway
mTOR↓,
mt-ROS↑, We demonstrated that HNK treatment suppresses mitochondrial respiration and increases generation of ROS in the mitochondria, leading to the induction of apoptosis in lung cancer cells
PI3K↓, inhibition of PI3K/Akt/ mTOR, EMT, and Wnt signaling pathways.
Wnt↓,

2884- HNK,    Honokiol inhibits EMT-mediated motility and migration of human non-small cell lung cancer cells in vitro by targeting c-FLIP
- in-vitro, Lung, A549 - in-vitro, Lung, H460
EMT↓, HNK inhibits EMT-mediated motility and migration of human NSCLC cells in vitro by targeting c-FLIP,
cFLIP↓,
N-cadherin↓, increased c-FLIP, N-cadherin (a mesenchymal marker), snail (a transcriptional modulator) and p-Smad2/3 expression, and decreased IκB levels in the cells; these changes were abrogated by co-treatment with HNK (30 μmol/L)
Snail↓,
p‑SMAD2↓,
p‑SMAD3↓,
IKKα↑,
TumCMig↓, HNK inhibits the migration of A549 and H460 cells induced by TNF-α+TGF-β1
NA↑,

2891- HNK,    Honokiol, an Active Compound of Magnolia Plant, Inhibits Growth, and Progression of Cancers of Different Organs
- Review, Var, NA
AntiCan↑, honokiol possesses anti-carcinogenic, anti-inflammatory, anti-oxidative, anti-angiogenic as well as inhibitory effect on malignant transformation of papillomas to carcinomas in vitro and in vivo animal models without any appreciable toxicity.
Inflam↓,
antiOx↑,
selectivity↑,
*toxicity↓,
cycD1↓, honokiol resulted in inhibition of UVB-induced expression levels of cyclins (cyclins D1, D2, and E) and CDKs in skin tumors
cycE↓,
CDK2↓,
CDK4↓,
TumMeta↓, Honokiol Inhibits Metastatic Potential of Melanoma Cells
NADPH↓, Honokiol not only reduces the NADPH oxidase activity
MMP2↓, honokiol treatment reduces the expression of MMP-2 and MMP-9
MMP9↓,
p‑mTOR↓, honokiol caused significant downregulation of mTOR phosphorylation
EGFR↓, honokiol decreases the expression levels of total EGFR
EMT↓, honokiol effectively inhibits EMT in breast cancer cells
SIRT1↑, onokiol increases the expressions of SIRT1 and SIRT3,
SIRT3↑,
EZH2↓, depletion of EZH2 by honokiol treatment inhibited cell proliferation
Snail↓, significantly down regulates Snail, vimentin, N-cadherin expression, and upregulates cytokeratin-18 and E-cadherin expression
Vim↓,
N-cadherin↓,
E-cadherin↑,
COX2↓, honokiol as an inhibitor of COX-2 expression
NF-kB↓, inhibited transcriptional activity of NF-jB,
*ROS↓, Inhibition of UVR-induced inflammatory mediators as well as ROS by honokiol treatment contributes to the prevention of UVR-induced skin tumor development
Ca+2↑, excessive influx of cytosolic calcium ion into the mitochondria triggers dysfunction of the mitochon- drial membrane permeabilization with mitochondrial ROS induction
ROS↑,

1119- HNK,    Honokiol inhibits epithelial—mesenchymal transition in breast cancer cells by targeting signal transducer and activator of transcription 3/Zeb1/E‐cadherin axis
- vitro+vivo, BC, NA
EMT↓,
MSCmark↓,
EM↑,
STAT3↓,
Zeb1↓,
E-cadherin↑,

1120- 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, NA
EMT↓,
CSCs↓, cancer stem cell (CSC) properties
TumCG↓,
miR-141↑,

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↓,
*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↓, ↓ 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↓,
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↑, ↑ 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↓, 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.

2866- HNK,    Honokiol and its analogues as anticancer compounds: Current mechanistic insights and structure-activity relationship
- Review, Var, NA
EMT↓, Honokiol regulates oncogenic pathways, inhibits EMT, and prevents metastasis.
TumMeta↓,
BioAv↑, The hydrophobicity of honokiol enables its rapid dissolution in lipids
BBB↑, crossing of physiological barriers, including the blood-brain barrier and cerebrospinal fluid


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 10

Results for Effect on Cancer/Diseased Cells:
Akt↓,1,   AMPK↑,1,   AntiCan↑,1,   antiOx↑,1,   Apoptosis↑,2,   ATG5↑,1,   ATG7↑,1,   BBB↓,1,   BBB↑,1,   BioAv↓,1,   BioAv↑,1,   Ca+2↑,2,   Casp3↑,3,   Casp9↑,1,   CD133↓,1,   CDK2↓,2,   CDK4↓,2,   CEBPB↓,1,   cFLIP↓,1,   chemoP↑,1,   ChemoSen↑,2,   cl‑CHOP↑,1,   cJun↑,1,   cMyc↓,1,   COX2↓,3,   CSCs↓,2,   cycD1↓,2,   cycE↓,1,   Cyt‑c↑,1,   Dose↝,1,   DR5↑,1,   E-cadherin↑,4,   EF-1α↓,1,   eff↑,1,   EGFR↓,2,   EM↑,1,   EMT↓,10,   ER Stress↑,3,   EZH2↓,1,   GRP78/BiP↑,1,   H3↑,1,   H4↑,1,   Half-Life↓,1,   Half-Life↝,1,   HATs↑,1,   HDAC↓,1,   HDAC3↓,1,   Hif1a↓,1,   IKKα↓,1,   IKKα↑,1,   Inflam↓,1,   JNK↑,1,   LC3II↑,1,   MAPK↓,1,   Mcl-1↓,1,   Mcl-1↑,1,   miR-141↑,1,   mitResp↓,1,   MMP↓,1,   MMP2↓,1,   MMP9↓,1,   MMPs↓,1,   MSCmark↓,1,   mTOR↓,1,   p‑mTOR↓,1,   mTORC1↓,1,   N-cadherin↓,4,   NA↑,1,   NADPH↓,1,   Nanog↓,1,   Nestin↓,1,   NF-kB↓,4,   NO↝,1,   NOTCH1↓,1,   NOTCH3↓,1,   NRF2↑,1,   OCR↓,1,   OCT4↓,1,   OS↑,1,   P-gp↓,1,   P21?,1,   P53↑,1,   p65↓,1,   cl‑PARP↑,1,   PCNA↓,1,   PGE2↓,2,   PI3K↓,2,   RadioS↑,1,   c-Raf↓,1,   RAS↓,1,   p‑RB1↓,1,   Rho↓,1,   ROCK1↓,1,   ROS↑,2,   mt-ROS↑,1,   selectivity↑,2,   SIRT1↑,1,   SIRT3↑,2,   Slug↓,1,   p‑SMAD2↓,2,   p‑SMAD3↓,2,   Snail↓,4,   SOX2↓,1,   SOX4↓,1,   STAT3↓,2,   p‑STAT3↓,1,   survivin↓,1,   TNF-α↓,1,   TumCCA↑,2,   TumCG↓,1,   TumCI↓,3,   TumCMig↓,3,   tumCV↓,1,   TumMeta↓,3,   VEGF↓,1,   VEGFR2↓,1,   Vim↓,2,   Wnt↓,2,   Zeb1↓,2,   β-catenin/ZEB1↓,2,   β-catenin/ZEB1↑,1,  
Total Targets: 121

Results for Effect on Normal Cells:
antiOx↑,1,   BBB↑,1,   Inflam↓,1,   neuroP↑,1,   ROS↓,2,   toxicity↓,1,  
Total Targets: 6

Scientific Paper Hit Count for: EMT, Epithelial-Mesenchymal Transition
10 Honokiol
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:94  Target#:96  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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