Honokiol / Casp3 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

Rank Pathway / Axis Cancer Cells Normal Cells Label Primary Interpretation Notes
1 Mitochondrial integrity / intrinsic apoptosis ↓ ΔΨm; ↑ cytochrome-c release; ↑ caspases ↔ largely preserved Driver Mitochondria-directed cytotoxicity Honokiol directly accumulates in mitochondria and initiates intrinsic apoptosis in cancer cells
2 Reactive oxygen species (ROS) ↑ ROS (secondary, stress-amplifying) ↔ buffered Secondary Mitochondrial stress amplification ROS elevation follows mitochondrial perturbation rather than acting as the initiating trigger
3 STAT3 signaling ↓ STAT3 activation ↔ minimal Driver Loss of survival and stemness signaling STAT3 suppression contributes to apoptosis, CSC targeting, and reduced proliferation
4 PI3K → AKT → mTOR axis ↓ AKT / ↓ mTOR ↔ adaptive suppression Secondary Growth and anabolic inhibition AKT/mTOR inhibition reinforces mitochondrial and apoptotic stress
5 NF-κB signaling ↓ NF-κB activation ↓ inflammatory NF-κB tone Secondary Suppression of survival transcription NF-κB inhibition contributes to chemosensitization and anti-inflammatory effects
6 Cell cycle regulation ↑ G0/G1 or G2/M arrest ↔ spared Phenotypic Cytostatic growth control Cell-cycle arrest reflects upstream signaling disruption
7 Autophagy ↑ autophagy (context-dependent) ↑ adaptive autophagy Adaptive Stress response vs death cooperation Autophagy may precede apoptosis or act as a transient survival response


Casp3, CPP32, Cysteinyl aspartate specific proteinase-3: Click to Expand ⟱
Source:
Type:
Also known as CP32.
Cysteinyl aspartate specific proteinase-3 (Caspase-3) is a common key protein in the apoptosis and pyroptosis pathways, and when activated, the expression level of tumor suppressor gene Gasdermin E (GSDME) determines the mechanism of tumor cell death.
As a key protein of apoptosis, caspase-3 can also cleave GSDME and induce pyroptosis. Loss of caspase activity is an important cause of tumor progression.
Many anticancer strategies rely on the promotion of apoptosis in cancer cells as a means to shrink tumors. Crucial for apoptotic function are executioner caspases, most notably caspase-3, that proteolyze a variety of proteins, inducing cell death. Paradoxically, overexpression of procaspase-3 (PC-3), the low-activity zymogen precursor to caspase-3, has been reported in a variety of cancer types. Until recently, this counterintuitive overexpression of a pro-apoptotic protein in cancer has been puzzling. Recent studies suggest subapoptotic caspase-3 activity may promote oncogenic transformation, a possible explanation for the enigmatic overexpression of PC-3. Herein, the overexpression of PC-3 in cancer and its mechanistic basis is reviewed; collectively, the data suggest the potential for exploitation of PC-3 overexpression with PC-3 activators as a targeted anticancer strategy.
Caspase 3 is the main effector caspase and has a key role in apoptosis. In many types of cancer, including breast, lung, and colon cancer, caspase-3 expression is reduced or absent.
On the other hand, some studies have shown that high levels of caspase-3 expression can be associated with a better prognosis in certain types of cancer, such as breast cancer. This suggests that caspase-3 may play a role in the elimination of cancer cells, and that therapies aimed at activating caspase-3 may be effective in treating certain types of cancer.
Procaspase-3 is a apoptotic marker protein.
Prognostic significance:
• High Cas3 expression: Associated with good prognosis and increased sensitivity to chemotherapy in breast, gastric, lung, and pancreatic cancers.
• Low Cas3 expression: Linked to poor prognosis and increased risk of recurrence in colorectal, hepatocellular carcinoma, ovarian, and prostate cancers.
Scientific Papers found: Click to Expand⟱
2881- HNK,    Honokiol Suppressed Pancreatic Cancer Progression via miR-101/Mcl-1 Axis
- in-vitro, PC, PANC1
tumCV↓, Casp3↑, Apoptosis↑, TumCCA↑, TumCI↓, Mcl-1↓, EMT↓,
2883- HNK,    Honokiol targets mitochondria to halt cancer progression and metastasis
- Review, Var, NA
ChemoSen↑, BBB↓, Ca+2↑, Cyt‑c↑, Casp3↑, chemoPv↑, OCR↓, mitResp↓, Apoptosis↑, RadioS↑, NF-kB↓, Akt↓, TNF-α↓, PGE2↓, VEGF↓, NO↝, COX2↓, RAS↓, EMT↓, Snail↓, N-cadherin↓, β-catenin/ZEB1↓, E-cadherin↑, ER Stress↑, p‑STAT3↓, EGFR↓, mTOR↓, mt-ROS↑, PI3K↓, Wnt↓,
2885- HNK,    Honokiol: a novel natural agent for cancer prevention and therapy
NF-kB↓, STAT3↓, EGFR↓, mTOR↓, BioAv↝, Inflam↓, TumCP↓, angioG↓, TumCI↓, TumMeta↓, cSrc↓, JAK1↓, JAK2↓, ERK↓, Akt↓, PTEN↑, ChemoSen↑, chemoP↑, COX2↓, PGE2↓, TNF-α↓, IL1β↓, IL6↓, Casp3↑, Casp8↑, Casp9↑, cl‑PARP↑, DNAdam↑, Cyt‑c↑, RadioS↑, RAS↓, BBB↑, BioAv↓, Half-Life↝, Half-Life↝, toxicity↓,
2894- HNK,    Pharmacological features, health benefits and clinical implications of honokiol
- Review, Var, NA - Review, AD, NA
*BioAv↓, *neuroP↑, *BBB↑, *ROS↓, *Keap1↑, *NRF2↑, *Casp3↓, *SIRT3↑, *Rho↓, *ERK↓, *NF-kB↓, angioG↓, RAS↓, PI3K↓, Akt↓, mTOR↓, *memory↑, *Aβ↓, *PPARγ↑, *PGC-1α↑, NF-kB↓, Hif1a↓, VEGF↓, HO-1↓, FOXM1↓, p27↑, P21↑, CDK2↓, CDK4↓, CDK6↓, cycD1/CCND1↓, Twist↓, MMP2↓, Rho↑, ROCK1↑, TumCMig↓, cFLIP↓, BMPs↑, OCR↑, ECAR↓, *AntiAg↑, *cardioP↑, *antiOx↑, *ROS↓, P-gp↓,
4238- HNK,    Neuropharmacological potential of honokiol and its derivatives from Chinese herb Magnolia species: understandings from therapeutic viewpoint
- Review, AD, NA - NA, Park, NA
*BDNF↑, *hepatoP↑, *ALAT↓, *AST↓, *TNF-α↓, *SIRT3↑, *Aβ↓, *Apoptosis↓, *ROS↓, *MMP↑, *Ca+2↓, *Casp3↓, *Ach↑, *PPARγ↑, *PGC-1α↑, *motorD↑, *TNF-α↓, *IL1β↓,
4659- HNK,    Honokiol Eliminates Human Oral Cancer Stem-Like Cells Accompanied with Suppression of Wnt/β-Catenin Signaling and Apoptosis Induction
- in-vitro, Oral, NA
cl‑Casp3↑, survivin↓, Bcl-2↓, CD44↓, Wnt↓, β-catenin/ZEB1↑, EMT↓, Slug↓, Snail↓, CSCs↓, Apoptosis↑,
1153- HNK,    Honokiol Eliminates Glioma/Glioblastoma Stem Cell-Like Cells via JAK-STAT3 Signaling and Inhibits Tumor Progression by Targeting Epidermal Growth Factor Receptor
- in-vitro, GBM, U251 - in-vitro, GBM, U87MG - in-vivo, NA, NA
tumCV↓, Apoptosis↑, TumCMig↓, TumCI↓, Bcl-2↓, EGFR↓, CD133↓, Nestin↓, Akt↓, ERK↓, Casp3↑, p‑STAT3↓, TumCG↓,
1286- HNK,    The natural product honokiol induces caspase-dependent apoptosis in B-cell chronic lymphocytic leukemia (B-CLL) cells
- in-vitro, CLL, NA
Apoptosis↑, Casp3↑, Casp8↑, Casp9↑, cl‑PARP↑, Bcl-2↓, BAX↑,
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↑, TumAuto↑, Apoptosis↑, TumCCA↑, GRP78/BiP↑, ROS↑, eff↓, p‑ERK↑, selectivity↑, Ca+2↑, MMP↓, Casp3↑, Casp9↑, cl‑PARP↑, Bcl-2↓, Bcl-xL↓, survivin↓, LC3B-II↑, ATG5↑, TumVol↓, TumW↓, ER Stress↑,
2879- HNK,    Honokiol Inhibits Lung Tumorigenesis through Inhibition of Mitochondrial Function
- in-vitro, Lung, H226 - in-vivo, NA, NA
tumCV↓, selectivity↑, TumCP↓, TumCCA↑, Apoptosis↑, mt-ROS↑, Casp3↑, Casp7↑, OCR↓, Cyt‑c↑, ATP↓, mitResp↓, AMP↑, AMPK↑,
2868- HNK,    Honokiol: A review of its pharmacological potential and therapeutic insights
- Review, Var, NA - Review, Sepsis, NA
*P-gp↓, *ROS↓, *TNF-α↓, *IL10↓, *IL6↓, eIF2α↑, CHOP↑, GRP78/BiP↑, BAX↑, cl‑Casp9↑, p‑PERK↑, ER Stress↑, Apoptosis↑, MMPs↓, cFLIP↓, CXCR4↓, Twist↓, HDAC↓, BMPs↑, p‑STAT3↓, mTOR↓, EGFR↓, NF-kB↓, Shh↓, VEGF↓, tumCV↓, TumCMig↓, TumCI↓, ERK↓, Akt↓, Bcl-2↓, Nestin↓, CD133↓, p‑cMET↑, RAS↑, chemoP↑, *NRF2↑, *NADPH↓, *p‑Rac1↓, *ROS↓, *IKKα↑, *NF-kB↓, *COX2↓, *PGE2↓, *Casp3↓, *hepatoP↑, *antiOx↑, *GSH↑, *Catalase↑, *RenoP↑, *ALP↓, *AST↓, *ALAT↓, *neuroP↑, *cardioP↑, *HO-1↑, *Inflam↓,
2867- HNK,    Honokiol ameliorates oxidative stress-induced DNA damage and apoptosis of c2c12 myoblasts by ROS generation and mitochondrial pathway
- in-vitro, Nor, C2C12
*antiOx↑, *ROS↓, *Bcl-2↑, *BAX↓, Casp9∅, Casp3∅, cl‑PARP∅, Cyt‑c?,
2865- HNK,    Liposomal Honokiol induces ROS-mediated apoptosis via regulation of ERK/p38-MAPK signaling and autophagic inhibition in human medulloblastoma
- in-vitro, MB, DAOY - vitro+vivo, NA, NA
BioAv↓, BioAv↓, TumCP↓, selectivity↑, P53↑, P21↑, CDK4↓, cycD1/CCND1↓, mtDam↑, ROS↑, eff↓, Casp3↑, BAX↑, LC3II↑, Beclin-1↑, ATG7↑, p62↑, eff↑, ChemoSen↑, *toxicity↓,
2864- HNK,    Honokiol: A Review of Its Anticancer Potential and Mechanisms
- Review, Var, NA
TumCCA↑, CDK2↓, EMT↓, MMPs↓, AMPK↑, TumCI↓, TumCMig↓, TumMeta↓, VEGFR2↓, *antiOx↑, *Inflam↓, *BBB↑, *neuroP↑, *ROS↓, Dose↝, selectivity↑, Casp3↑, Casp9↑, NOTCH1↓, cycD1/CCND1↓, cMyc↓, P21?, DR5↑, cl‑PARP↑, P53↑, Mcl-1↑, p65↓, NF-kB↓, ROS↑, JNK↑, NRF2↑, cJun↑, EF-1α↓, MAPK↓, PI3K↓, mTORC1↓, CSCs↓, OCT4↓, Nanog↓, SOX4↓, STAT3↓, CDK4↓, p‑RB1↓, PGE2↓, COX2↓, β-catenin/ZEB1↑, IKKα↓, HDAC↓, HATs↑, H3↑, H4↑, LC3II↑, c-Raf↓, SIRT3↑, Hif1a↓, ER Stress↑, GRP78/BiP↑, cl‑CHOP↑, MMP↓, PCNA↓, Zeb1↓, NOTCH3↓, CD133↓, Nestin↓, ATG5↑, ATG7↑, survivin↓, ChemoSen↑, SOX2↓, OS↑, P-gp↓, Half-Life↓, Half-Life↝, eff↑, BioAv↓,

Showing Research Papers: 1 to 14 of 14

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 14

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

HO-1↓, 1,   NRF2↑, 1,   ROS↑, 3,   mt-ROS↑, 2,   SIRT3↑, 1,  

Mitochondria & Bioenergetics ⓘ

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

Core Metabolism/Glycolysis ⓘ

AMP↑, 1,   AMPK↑, 2,   ATG7↑, 2,   cMyc↓, 1,   ECAR↓, 1,  

Cell Death ⓘ

Akt↓, 5,   Apoptosis↑, 8,   BAX↑, 3,   Bcl-2↓, 5,   Bcl-xL↓, 1,   Casp3↑, 9,   Casp3∅, 1,   cl‑Casp3↑, 1,   Casp7↑, 1,   Casp8↑, 2,   Casp9↑, 4,   Casp9∅, 1,   cl‑Casp9↑, 1,   cFLIP↓, 2,   Cyt‑c↑, 3,   Cyt‑c?, 1,   DR5↑, 1,   JNK↑, 1,   MAPK↓, 1,   Mcl-1↓, 1,   Mcl-1↑, 1,   p27↑, 1,   survivin↓, 3,   TumCD↑, 1,  

Kinase & Signal Transduction ⓘ

cSrc↓, 1,   EF-1α↓, 1,  

Transcription & Epigenetics ⓘ

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

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   cl‑CHOP↑, 1,   eIF2α↑, 1,   ER Stress↑, 4,   GRP78/BiP↑, 3,   p‑PERK↑, 1,  

Autophagy & Lysosomes ⓘ

ATG5↑, 2,   Beclin-1↑, 1,   LC3B-II↑, 1,   LC3II↑, 2,   p62↑, 1,   TumAuto↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   P53↑, 2,   cl‑PARP↑, 4,   cl‑PARP∅, 1,   PCNA↓, 1,  

Cell Cycle & Senescence ⓘ

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

Proliferation, Differentiation & Cell State ⓘ

CD133↓, 3,   CD44↓, 1,   p‑cMET↑, 1,   CSCs↓, 2,   EMT↓, 4,   ERK↓, 3,   p‑ERK↑, 1,   FOXM1↓, 1,   HDAC↓, 2,   mTOR↓, 4,   mTORC1↓, 1,   Nanog↓, 1,   Nestin↓, 3,   NOTCH1↓, 1,   NOTCH3↓, 1,   OCT4↓, 1,   PI3K↓, 3,   PTEN↑, 1,   RAS↓, 3,   RAS↑, 1,   Shh↓, 1,   SOX2↓, 1,   STAT3↓, 2,   p‑STAT3↓, 3,   TumCG↓, 1,   Wnt↓, 2,  

Migration ⓘ

Ca+2↑, 2,   E-cadherin↑, 1,   MMP2↓, 1,   MMPs↓, 2,   N-cadherin↓, 1,   Rho↑, 1,   ROCK1↑, 1,   Slug↓, 1,   Snail↓, 2,   SOX4↓, 1,   TumCI↓, 5,   TumCMig↓, 4,   TumCP↓, 3,   TumMeta↓, 2,   Twist↓, 2,   Zeb1↓, 1,   β-catenin/ZEB1↓, 1,   β-catenin/ZEB1↑, 2,  

Angiogenesis & Vasculature ⓘ

angioG↓, 2,   EGFR↓, 4,   Hif1a↓, 2,   NO↝, 1,   VEGF↓, 3,   VEGFR2↓, 1,  

Barriers & Transport ⓘ

BBB↓, 1,   BBB↑, 1,   P-gp↓, 2,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 3,   CXCR4↓, 1,   IKKα↓, 1,   IL1β↓, 1,   IL6↓, 1,   Inflam↓, 1,   JAK1↓, 1,   JAK2↓, 1,   NF-kB↓, 5,   p65↓, 1,   PGE2↓, 3,   TNF-α↓, 2,  

Hormonal & Nuclear Receptors ⓘ

CDK6↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 4,   BioAv↝, 1,   ChemoSen↑, 4,   Dose↝, 1,   eff↓, 2,   eff↑, 2,   Half-Life↓, 1,   Half-Life↝, 3,   RadioS↑, 2,   selectivity↑, 4,  

Clinical Biomarkers ⓘ

BMPs↑, 2,   EGFR↓, 4,   FOXM1↓, 1,   IL6↓, 1,  

Functional Outcomes ⓘ

chemoP↑, 2,   chemoPv↑, 1,   OS↑, 1,   toxicity↓, 1,   TumVol↓, 1,   TumW↓, 1,  
Total Targets: 158

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 4,   Catalase↑, 1,   GSH↑, 1,   HO-1↑, 1,   Keap1↑, 1,   NRF2↑, 2,   ROS↓, 7,   SIRT3↑, 2,  

Mitochondria & Bioenergetics ⓘ

MMP↑, 1,   PGC-1α↑, 2,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 2,   NADPH↓, 1,   PPARγ↑, 2,  

Cell Death ⓘ

Apoptosis↓, 1,   BAX↓, 1,   Bcl-2↑, 1,   Casp3↓, 3,  

Transcription & Epigenetics ⓘ

Ach↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 1,  

Migration ⓘ

AntiAg↑, 1,   Ca+2↓, 1,   p‑Rac1↓, 1,   Rho↓, 1,  

Barriers & Transport ⓘ

BBB↑, 2,   P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IKKα↑, 1,   IL10↓, 1,   IL1β↓, 1,   IL6↓, 1,   Inflam↓, 2,   NF-kB↓, 2,   PGE2↓, 1,   TNF-α↓, 3,  

Synaptic & Neurotransmission ⓘ

BDNF↑, 1,  

Protein Aggregation ⓘ

Aβ↓, 2,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 2,   ALP↓, 1,   AST↓, 2,   IL6↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 2,   hepatoP↑, 2,   memory↑, 1,   motorD↑, 1,   neuroP↑, 3,   RenoP↑, 1,   toxicity↓, 1,  
Total Targets: 48

Scientific Paper Hit Count for: Casp3, CPP32, Cysteinyl aspartate specific proteinase-3
14 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#:42  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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