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


RadioS, RadioSensitizer: Click to Expand ⟱
Source:
Type:
A radiosensitizer is an agent that makes cancer cells more sensitive to the damaging effects of radiation therapy. By using a radiosensitizer, clinicians aim to enhance the effectiveness of radiation treatment by either increasing the damage incurred by tumor cells or by interfering with the cancer cells’ repair mechanisms. This can potentially allow for lower doses of radiation, reduced side effects, or improved treatment outcomes.
Pathways that help Radiosensitivity: downregulating HIF-1α, increase SIRT1, Txr

List of Natural Products with radiosensitizing properties:
-Curcumin:modulate NF-κB, STAT3 and has been shown in preclinical studies to enhance the effects of radiation by inhibiting cell survival pathways.
-Resveratrol:
-EGCG:
-Quercetin:
-Genistein:
-Parthenolide:

How radiosensitizers inhibit the thioredoxin (Trx) system in cellular contexts. Notable radiosensitizers, including:
-gold nanoparticles (GNPs),
-gold triethylphosphine cyanide ([Au(SCN) (PEt3)]),
-auranofin, ceria nanoparticles (CONPs),
-curcumin and its derivatives,
-piperlongamide,
-indolequinone derivatives,
-micheliolide,
-motexafin gadolinium, and
-ethane selenide selenidazole derivatives (SeDs)
Scientific Papers found: Click to Expand⟱
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↓,

2885- HNK,    Honokiol: a novel natural agent for cancer prevention and therapy
NF-kB↓, Honokiol targets multiple signaling pathways including nuclear factor kappa B (NF-κB), signal transducers and activator of transcription 3 (STAT3), epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (m-TOR)
STAT3↓,
EGFR↓,
mTOR↓,
BioAv↝, honokiol has revealed a desirable spectrum of bioavailability after intravenous administration in animal models, thus making it a suitable agent for clinical trials
Inflam↓, inflammation, proliferation, angiogenesis, invasion and metastasis.
TumCP↓,
angioG↓,
TumCI↓,
TumMeta↓,
cSrc↓, STAT3 inhibition by honokiol has also been correlated with the repression of upstream protein tyrosine kinases c-Src, JAK1 and JAK2
JAK1↓,
JAK2↓,
ERK↓, by inhibiting ERK and Akt pathways (31) or by upregulation of PTEN
Akt↓,
PTEN↑,
ChemoSen↑, Chemopreventive/ chemotherapeutic effects of honokiol in various malignancies: preclinical studies
chemoP↑,
COX2↓, honokiol was found to inhibit UVB-induced expression of cyclooxygenase-2, prostaglandin E2, proliferating cell nuclear antigen and pro-inflammatory cytokines, such as TNF-α, interleukin (IL)-1β and IL-6 in the skin
PGE2↓,
TNF-α↓,
IL1β↓,
IL6↓,
Casp3↑, release of caspases-3, -8 and -9as well as poly (ADP-ribose) polymerase (PARP) cleavage and p53 activation upon honokiol treatment that led to DNA fragmentation
Casp8↑,
Casp9↑,
cl‑PARP↑,
DNAdam↑,
Cyt‑c↑, translocation of cytochrome c to cytosol in human melanoma cell lines
RadioS↑, liposomal honokiol for 24 h showed a higher radiation enhancement ratio (~ two-fold) as compared to the radiation alone,
RAS↓, Honokiol also caused suppression of Ras activation
BBB↑, honokiol could effectively cross BBB and BCSFB and inhibit brain tumor growth
BioAv↓, Due to the concerns about poor aqueous solubility, liposomal formulations of honokiol have been developed and tested for their pharmacokinetics
Half-Life↝, In another comparative study, plasma honokiol concentrations was maintained above 30 and 10 μg/mL for 24 and 48 hours, respectively, in liposomal honokiol-treated mice, whereas it fell quickly (less than 5 μg/mL) by 12 hours in free honokiol-treated
Half-Life↝, free honokiol has poor GIT absorption, bio-transformed in liver to mono-glucuronide honokiol and sulphated mono-hydroxyhonokiol, ~ 50% is secreted in bile, ~ 60-65% plasma protein bound with elimination half life of (t1/2) of 49.05 – 56.24 minutes.
toxicity↓, These studies suggest that honokiol either alone or as a part of magnolia bark extract does not induce toxicity in animal models and thus could be clinically safe

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


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 3

Results for Effect on Cancer/Diseased Cells:
Akt↓,2,   angioG↓,1,   Apoptosis↑,1,   BBB↓,1,   BBB↑,1,   BioAv↓,1,   BioAv↝,1,   Ca+2↑,1,   Casp3↑,2,   Casp8↑,1,   Casp9↑,1,   chemoP↑,2,   ChemoSen↑,2,   COX2↓,2,   cSrc↓,1,   Cyt‑c↑,2,   DNAdam↑,1,   E-cadherin↑,1,   EGFR↓,2,   EMT↓,1,   ER Stress↑,1,   ERK↓,1,   Half-Life↝,2,   Hif1a↓,1,   IL1β↓,1,   IL6↓,1,   Inflam↓,1,   JAK1↓,1,   JAK2↓,1,   mitResp↓,1,   mTOR↓,2,   N-cadherin↓,1,   NF-kB↓,2,   NO↝,1,   OCR↓,1,   cl‑PARP↑,1,   PGE2↓,2,   PI3K↓,1,   PTEN↑,1,   RadioS↑,3,   RAS↓,2,   mt-ROS↑,1,   Snail↓,1,   STAT3↓,1,   p‑STAT3↓,1,   TNF-α↓,2,   toxicity↓,1,   TumCI↓,1,   TumCP↓,1,   TumMeta↓,1,   VEGF↓,1,   Wnt↓,1,   β-catenin/ZEB1↓,1,  
Total Targets: 53

Results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: RadioS, RadioSensitizer
3 Honokiol
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:94  Target#:1107  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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