Magnolol / Apoptosis Cancer Research Results

MAG, Magnolol: Click to Expand ⟱
Features:
Lignan found in bark of some magnolia species.
Magnolol (MAG) — a bioactive biphenolic compound from Magnolia officinalis
derived from the bark (roots and branches) of Magnolia species such as M. officinalis, M. obovata, and M. grandiflora
The two main bioactive compounds isolated from these plants are MAG (5,5ʹ-diallyl-2,2ʹ-dihydroxybiphenyl) and Honokiol (3,5ʹ-diallyl-4,2ʹ-dihydroxybiphenyl) (Fig. 1) which are phenolic regioisomers.
In the bark extracts of Magnolia plants, the composition of MAG ranges from 1 to 10%, while Honokiol comprises 1 to 5%
Magnolol is a biphenolic neolignan isolated from the bark of Magnolia officinalis. It is structurally related to honokiol and is studied for anti-inflammatory, antioxidant, antimicrobial, and neuroactive effects. In preclinical oncology models, magnolol is reported to modulate NF-κB, STAT3, PI3K/AKT, MAPK, Wnt/β-catenin, and redox pathways, with downstream effects on cell-cycle arrest, apoptosis, invasion/EMT, and angiogenesis. Oral bioavailability is limited and many cytotoxic concentrations reported in vitro are in the tens of µM range, often above typical systemic levels from standard supplementation.

major pathways and molecular targets involved in magnolol’s anticancer actions:
-Apoptosis: ↑ Bax, ↓ Bcl-2, ↑ cytochrome c, ↑ caspase-9, ↑ caspase-3
-Arrests cell cycle at G0/G1 or G2/M phase:↓ Cyclin D1, CDK4, CDK6, Cyclin B1, CDK1
-Inhibits NF-κB activation: ↓ IκBα, COX-2, TNF-α
-Inhibits PI3K, Akt, and mTOR phosphorylation
-Suppresses angiogenesis: ↓ Bcl-XL, Mcl-1, VEGF, cyclin D1
-Inhibits β-catenin nuclear translocation
-increase ROS production in tumor cells → triggers mitochondrial apoptosis
-Magnolol activates Nrf2 in normal cells → upregulates HO-1, NQO1: Protects normal tissue from oxidative stress during chemotherapy or inflammation.

Most in-vitro IC50 values fall in the 10–100 µM range, often above typical systemic exposure.

Rank Pathway / Axis Cancer / Tumor Context Normal Tissue Context TSF Primary Effect Notes / Interpretation
1 NF-κB inflammatory / survival transcription NF-κB ↓; COX-2, cytokines, Bcl-2 family ↓ (reported) Inflammation tone ↓ R, G Anti-inflammatory + anti-survival transcription One of the most consistently reported mechanisms in both inflammatory and tumor models.
2 STAT3 signaling STAT3 phosphorylation ↓ (reported) R, G Oncogenic transcription suppression Reported in several cancer cell systems; contributes to reduced proliferation and survival signaling.
3 PI3K → AKT → mTOR pathway PI3K/AKT signaling ↓ (model-dependent) R, G Growth/survival modulation Frequently described as downstream of inflammatory pathway suppression; context-dependent strength.
4 Nrf2 / ARE antioxidant response Modulation context-dependent; may decrease oxidative stress or alter redox tone Nrf2 ↑; HO-1 ↑; GSH ↑ (cytoprotective) R, G Redox regulation Magnolol activates Nrf2 in non-malignant oxidative stress models; tumor direction varies and may influence therapy sensitivity.
5 MAPK pathways (ERK / JNK / p38) MAPK modulation (stress activation or ERK suppression; context-dependent) P, R, G Signal reprogramming JNK/p38 activation and ERK modulation reported variably depending on cell type and dose.
6 Cell-cycle arrest (G0/G1 or G2/M) Cell-cycle arrest ↑ (reported) G Cytostasis Associated with Cyclin D1/CDK modulation and checkpoint protein regulation.
7 Intrinsic apoptosis (mitochondrial pathway) Apoptosis ↑; caspases ↑; Bax/Bcl-2 ratio ↑ (reported) ↔ (generally less activation) G Cell death execution Often downstream of survival pathway inhibition and ROS signaling shifts.
8 ROS / redox modulation ROS ↑ in some tumor models; antioxidant effects in non-tumor systems Oxidative stress ↓ in inflammatory models P, R, G Context-dependent redox modulation Biphasic redox behavior similar to other polyphenols; not a universally tumor-selective pro-oxidant.
9 Wnt/β-catenin signaling β-catenin signaling ↓ (reported) G Proliferation/invasion modulation Reported particularly in colorectal and hepatocellular carcinoma models; keep model-qualified.
10 Invasion / metastasis (MMPs / EMT) MMP2/MMP9 ↓; EMT markers ↓; migration ↓ (reported) G Anti-invasive phenotype Often secondary to NF-κB/STAT3 pathway suppression.
11 Bioavailability constraint Limited oral bioavailability; rapid metabolism Translation constraint Plasma levels after oral dosing are typically lower than many in-vitro cytotoxic concentrations.

Time-Scale Flag (TSF): P / R / G

  • P: 0–30 min (rapid signaling/redox interactions)
  • R: 30 min–3 hr (acute transcription and stress-response signaling shifts)
  • G: >3 hr (gene-regulatory adaptation and phenotype outcomes)


Apoptosis, Apoptosis: Click to Expand ⟱
Source:
Type: type of cell death
Situation in which a cell actively pursues a course toward death upon receiving certain stimuli.
Cancer is one of the scenarios where too little apoptosis occurs, resulting in malignant cells that will not die.


Scientific Papers found: Click to Expand⟱
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↑, eff↑, TumCP↓, TumCCA↓, cycD1/CCND1↓, Pyro↑, Apoptosis↑, cl‑GSDME↑, Bcl-2↓, Cyt‑c↑, Casp9↑, TumCG↓,
4531- MAG,    Magnolol-induced apoptosis in HCT-116 colon cancer cells is associated with the AMP-activated protein kinase signaling pathway
- in-vitro, CRC, HCT116
Apoptosis↑, DNAdam↑, Casp3↑, cl‑PARP↑, p‑AMPK↑, Bcl-2↓, P53↑, BAX↑, Cyt‑c↑, TumCMig↓, TumCI↓,
4526- MAG,  HNK,    Targeting apoptosis pathways in cancer with magnolol and honokiol, bioactive constituents of the bark of Magnolia officinalis
- Review, Var, NA
*antiOx↑, *Inflam↓, *Bacteria↓, *toxicity↓, AntiTum↑, Apoptosis↑, DR5↝,
4527- MAG,    Magnolol inhibits growth and induces apoptosis in esophagus cancer KYSE-150 cell lines via the MAP kinase pathway
- in-vitro, ESCC, TE1 - in-vitro, ESCC, Eca109 - vitro+vivo, SCC, KYSE150
TumCP↓, TumCMig↓, MMP2↓, Apoptosis↑, cl‑Casp3↑, cl‑Casp9↑, BAX↑, Bcl-2↓, p‑p38↓, TumCG↓,
4528- MAG,    Pharmacology, Toxicity, Bioavailability, and Formulation of Magnolol: An Update
- Review, Nor, NA
*Inflam↑, *cardioP↑, *angioG↓, *antiOx↑, *neuroP↑, *Bacteria↓, AntiTum↑, TumCG↓, TumCMig↓, TumCI↓, Apoptosis↑, E-cadherin↑, NF-kB↓, TumCCA↑, cycD1/CCND1↓, PCNA↓, Ki-67↓, MMP2↓, MMP7↓, MMP9↓, TumCG↓, Casp3↑, NF-kB↓, Akt↓, mTOR↓, LDH↓, Ca+2↑, eff↑, *toxicity↓, *BioAv↝, *PGE2↓, *TLR2↓, *TLR4↓, *MAPK↓, *PPARγ↓,
5252- MAG,    Insights on the Multifunctional Activities of Magnolol
- Review, Var, NA
BioAv↓, *Inflam↓, *Bacteria↓, *antiOx↑, *neuroP↑, *cardioP↑, CYP1A1↓, *PPARγ↑, *NF-kB↓, *COX2↓, *iNOS↓, *ROS↓, Apoptosis↑, TumCCA↑, cycD1/CCND1↓, cycA1/CCNA1↓, CDK2↓, P21↑, TumCG↓, TumCMig↓, TumCI↓, Ki-67↓, PCNA↓, MMP2↓, MMP9↓, MMP7↓, DNAdam↑, MMP↓, TumCP↓, selectivity↑, PI3K↓, Akt↓, H2O2↓, Hif1a↓, *BDNF↑, *NRF2↑, *AChE↑,
4533- MAG,    Magnolol, a natural compound, induces apoptosis of SGC-7901 human gastric adenocarcinoma cells via the mitochondrial and PI3K/Akt signaling pathways
- in-vitro, GC, SGC-7901
AntiCan↑, DNAdam↑, Apoptosis↑, TumCCA↑, Bax:Bcl2↑, MMP↓, Casp3↑, PI3K↓, Akt↓,
4534- MAG,    Molecular mechanisms of apoptosis induced by magnolol in colon and liver cancer cells
- in-vitro, Liver, HepG2 - in-vitro, CRC, COLO205
AntiCan↑, Apoptosis↑, selectivity↑, Ca+2↑, Cyt‑c↑, Casp3↑, Casp8↑, Casp9↑, Bcl-2↓,
4536- MAG,    Magnolol suppresses proliferation of cultured human colon and liver cancer cells by inhibiting DNA synthesis and activating apoptosis
- in-vitro, Liver, HepG2 - in-vivo, CRC, COLO205
AntiCan↑, selectivity↑, TumCCA↑, P21↑, Apoptosis↑,
4537- MAG,    Effects of magnolol on UVB-induced skin cancer development in mice and its possible mechanism of action
- in-vivo, Melanoma, NA - in-vitro, Melanoma, A431
*cl‑Casp8↑, *PARP↑, *P21↑, tumCV↓, TumCP↓, TumCCA↑, CycB/CCNB1↓, cycA1/CCNA1↓, CDK4↓, CDC2↓, P21↑, Apoptosis↑,
4517- MAG,    Mitochondrion-targeted magnolol derivatives exert synergistic anticancer activity by modulating energy metabolism and tumor microenvironment
- vitro+vivo, Var, NA
eff↑, AntiCan↑, ROS↑, ER Stress↑, Apoptosis↑,
4516- MAG,    Magnolol Induces Apoptosis and Suppresses Immune Evasion in Non-small Cell Lung Cancer Xenograft Models
- in-vivo, NSCLC, NA
selectivity↑, Apoptosis↑, TumCCA↑, Casp3↑, cycD1/CCND1↓, CDK4↓, VEGF↓, FOXP3↓, IDO1↓,
4515- MAG,    Magnolol as a Potential Anticancer Agent: A Proposed Mechanistic Insight
- Review, Var, NA
AntiCan↑, TumCP↓, TumCCA↑, Apoptosis↑, TumCMig↑, angioG↓, PI3K↓, Akt↓, mTOR↓, MAPK↓, NF-kB↓,

Showing Research Papers: 1 to 13 of 13

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 13

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress

CYP1A1↓, 1,   H2O2↓, 1,   ROS↑, 1,  

Mitochondria & Bioenergetics

CDC2↓, 1,   MMP↓, 2,  

Core Metabolism/Glycolysis

p‑AMPK↑, 1,   IDO1↓, 1,   LDH↓, 1,  

Cell Death

Akt↓, 4,   Apoptosis↑, 13,   BAX↑, 2,   Bax:Bcl2↑, 1,   Bcl-2↓, 4,   Casp3↑, 5,   cl‑Casp3↑, 1,   Casp8↑, 1,   Casp9↑, 2,   cl‑Casp9↑, 1,   Cyt‑c↑, 3,   DR5↝, 1,   cl‑GSDME↑, 1,   MAPK↓, 1,   p‑p38↓, 1,   Pyro↑, 1,  

Transcription & Epigenetics

tumCV↓, 1,  

Protein Folding & ER Stress

ER Stress↑, 1,  

DNA Damage & Repair

DNAdam↑, 3,   P53↑, 1,   cl‑PARP↑, 1,   PCNA↓, 2,  

Cell Cycle & Senescence

CDK2↓, 1,   CDK4↓, 2,   cycA1/CCNA1↓, 2,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 4,   P21↑, 3,   TumCCA↓, 1,   TumCCA↑, 7,  

Proliferation, Differentiation & Cell State

mTOR↓, 2,   PI3K↓, 3,   TumCG↓, 5,  

Migration

Ca+2↑, 2,   E-cadherin↑, 1,   Ki-67↓, 2,   MMP2↓, 3,   MMP7↓, 2,   MMP9↓, 2,   TumCI↓, 3,   TumCMig↓, 4,   TumCMig↑, 1,   TumCP↓, 5,  

Angiogenesis & Vasculature

angioG↓, 1,   Hif1a↓, 1,   VEGF↓, 1,  

Immune & Inflammatory Signaling

FOXP3↓, 1,   NF-kB↓, 3,  

Drug Metabolism & Resistance

BioAv↓, 1,   eff↑, 3,   selectivity↑, 4,  

Clinical Biomarkers

Ki-67↓, 2,   LDH↓, 1,  

Functional Outcomes

AntiCan↑, 6,   AntiTum↑, 2,  
Total Targets: 63

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

antiOx↑, 3,   NRF2↑, 1,   ROS↓, 1,  

Core Metabolism/Glycolysis

PPARγ↓, 1,   PPARγ↑, 1,  

Cell Death

cl‑Casp8↑, 1,   iNOS↓, 1,   MAPK↓, 1,  

DNA Damage & Repair

PARP↑, 1,  

Cell Cycle & Senescence

P21↑, 1,  

Angiogenesis & Vasculature

angioG↓, 1,  

Immune & Inflammatory Signaling

COX2↓, 1,   Inflam↓, 2,   Inflam↑, 1,   NF-kB↓, 1,   PGE2↓, 1,   TLR2↓, 1,   TLR4↓, 1,  

Synaptic & Neurotransmission

AChE↑, 1,   BDNF↑, 1,  

Drug Metabolism & Resistance

BioAv↝, 1,  

Functional Outcomes

cardioP↑, 2,   neuroP↑, 2,   toxicity↓, 2,  

Infection & Microbiome

Bacteria↓, 3,  
Total Targets: 25

Scientific Paper Hit Count for: Apoptosis, Apoptosis
13 Magnolol
2 Honokiol
1 Baicalin
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#:121  Target#:14  State#:%  Dir#:2
wNotes=0 sortOrder:rid,rpid

 

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