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


MMP9, MMP9: Click to Expand ⟱
Source: HalifaxProj(suppress)
Type:
Matrix metalloproteinase-9 (MMP-9) is an enzyme that plays a significant role in the degradation of extracellular matrix components.
MMP-9 facilitates the breakdown of the extracellular matrix, which can enable cancer cells to invade surrounding tissues and spread to distant sites (metastasis).
Elevated levels of MMP-9 have been associated with poor prognosis in several cancers, including breast, lung, and colorectal cancers.
MMP2 and MMP9: two enzymes are critical to tumor invasion.
Scientific Papers found: Click to Expand⟱
2878- HNK,    Suppressing migration and invasion of H1299 lung cancer cells by honokiol through disrupting expression of an HDAC6-mediated matrix metalloproteinase 9
- in-vitro, Lung, H1299
TumCMig↓, migration and invasion ability of H1299 lung cancer was suppressed by noncytotoxic concentrations of honokiol treatment.
TumCI↓,
MMP9↓, proteolytic activity of MMP-9, rather than MMP-2, was inhibited in honokiol-treated H1299 cells.
α-tubulin↑, Furthermore, the expression of specific histone deacetylases 6 (HDAC6) substrate, acetyl-α-tubulin, was accumulated after honokiol incubation
HDAC6↓, suppression of migration and invasion activities by honokiol was through inhibiting HDAC6-mediated Hsp90/MMP-9 interaction and followed by MMP-9 degradation in lung cancer.
HSP90↓, Honokiol-suppressed MMP-9 expression was through the inhibition of HDAC6/Hsp90 signaling pathway

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↑,

2897- HNK,    Honokiol Inhibits Proliferation, Invasion and Induces Apoptosis Through Targeting Lyn Kinase in Human Lung Adenocarcinoma Cells
- in-vitro, Lung, PC9 - in-vitro, Lung, A549
TumCP↓, Honokiol Inhibits Cell Proliferation in Both A549 Cells and PC-9 Cells
Apoptosis↑, Honokiol Induces Apoptosis in PC-9 Cells
EGFR↓, Honokiol Suppresses Lyn Kinase and EGFR Signaling Pathway in PC-9 Cells
PI3K↓, led to a reduction of EGFR/PI3K/AKT and STAT3, and their phosphorylation status.
Akt↓,
STAT3↓,
TumCI↓, honokiol inhibits PC-9 cell proliferation, invasion and induces apoptosis through targeting Lyn kinase and Lyn-mediated EGFR signaling pathway.
TNF-α↑, Honokiol has efficacy to enhance the activation of TNF-α, in this way, honokiol inhibits activation of NF-κB and Akt. As a result, honokiol dramatically decreases expression level of NF-κB target genes, such as VEGF, MMP-9, and COX-2.
NF-kB↓,
VEGF↓,
MMP9↓,
COX2↓,

2898- HNK,    Honokiol Suppression of Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Gastric Cancer Cell Biological Activity and Its Mechanism
- in-vitro, GC, AGS - in-vitro, GC, NCI-N87 - in-vitro, BC, MGC803 - in-vitro, GC, SGC-7901
TumCP↓, 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

1087- HNK,    Honokiol Inhibits Non-Small Cell Lung Cancer Cell Migration by Targeting PGE2-Mediated Activation of β-Catenin Signaling
- in-vitro, Lung, A549 - in-vitro, Lung, H1299 - in-vitro, Lung, H460 - in-vitro, Lung, H226
TumCMig↓,
COX2↓,
PGE2↓,
NF-kB↓,
p65↓,
β-catenin/ZEB1↓,
MMP2↓,
MMP9↓,

2874- HNK,    Suppressing migration and invasion of H1299 lung cancer cells by honokiol through disrupting expression of an HDAC6‐mediated matrix metalloproteinase 9
- in-vitro, Lung, H1299
MMP9↓, Honokiol‐inhibited MMP‐9 expression was through promoting MMP‐9 protein degradation rather than suppressing transcription mechanism
α-tubulin↑, Furthermore, the expression of specific histone deacetylases 6 (HDAC6) substrate, acetyl‐α‐tubulin, was accumulated after honokiol incubation.
TumCI↓, honokiol‐suppressed MMP‐9 expression and invasion ability of H1299 lung cancer cells
HDAC6↓, Honokiol‐suppressed MMP‐9 expression was through the inhibition of HDAC6/Hsp90 signaling pathway
HSP90↓,
TumCMig↓, Honokiol inhibited lung cancer cell migration and invasion
EGFR↓, Honokiol has been verified to inhibit the EGFR‐mediated signaling pathwa


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 6

Results for Effect on Cancer/Diseased Cells:
Akt↓,2,   AntiCan↑,1,   antiOx↑,1,   Apoptosis↑,2,   Ca+2↑,1,   CDK2↓,1,   CDK4↓,1,   COX2↓,3,   cycD1↓,1,   cycE↓,1,   E-cadherin↑,1,   EGFR↓,3,   EMT↓,1,   EZH2↓,1,   HDAC6↓,2,   HER2/EBBR2↓,1,   HSP90↓,2,   Inflam↓,1,   MMP2↓,2,   MMP9↓,6,   p‑mTOR↓,1,   N-cadherin↓,1,   NADPH↓,1,   NF-kB↓,3,   P21↑,1,   p65↓,1,   PGE2↓,1,   PI3K↓,2,   ROS↑,1,   selectivity↑,1,   SIRT1↑,1,   SIRT3↑,1,   Snail↓,1,   STAT3↓,1,   TNF-α↑,1,   TumCCA↑,1,   TumCI↓,4,   TumCMig↓,4,   TumCP↓,2,   TumMeta↓,1,   VEGF↓,1,   Vim↓,1,   α-tubulin↑,2,   β-catenin/ZEB1↓,1,  
Total Targets: 44

Results for Effect on Normal Cells:
ROS↓,1,   toxicity↓,1,  
Total Targets: 2

Scientific Paper Hit Count for: MMP9, MMP9
6 Honokiol
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:94  Target#:203  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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