Magnetic Fields / JNK Cancer Research Results

MF, Magnetic Fields: Click to Expand ⟱
Features: Therapy

Magnetic Fields — externally applied static or time-varying magnetic fields used to alter cellular signaling, redox state, ion handling, membrane behavior, metabolism, or neural activity without introducing a chemical agent. They are a physical therapeutic modality and include static magnetic fields (SMF), extremely-low-frequency magnetic fields (ELF-MF), pulsed electromagnetic fields (PEMF), and other non-rotating oscillating/time-varying magnetic fields. Common abbreviations include MF, SMF, ELF-MF, EMF, and PEMF. Biological effects are strongly dependent on field strength, frequency, waveform, gradient, duty cycle, exposure duration, and tissue or cell type. Rotating magnetic fields are excluded here because they are represented separately as pid 192; magnetic-nanoparticle-dependent magnetothermal or magnetomechanical effects are also better assigned primarily to the magnetic nanoparticle product.

Primary mechanisms (ranked):

  1. Redox modulation and ROS perturbation, including radical-pair and mitochondrial mechanisms; cancer cells may develop sustained oxidative stress whereas normal cells frequently show adaptive antioxidant responses.
  2. Ca²⁺ and ion-channel modulation, particularly TRPC, voltage-gated channels, intracellular Ca²⁺ handling, and ER–mitochondrial Ca²⁺ communication.
  3. Mitochondrial and bioenergetic modulation, including membrane potential, electron transport, ATP production, mitochondrial permeability, and metabolic reprogramming.
  4. Cell proliferation, cell-cycle, apoptosis, and senescence signaling through pathways including EGFR/PI3K/AKT/mTOR, MAPK/ERK, caspases, PARP, Bax and survivin.
  5. Membrane permeability and drug-uptake modulation, producing context-dependent chemosensitization to agents including doxorubicin, etoposide and methotrexate.
  6. Inflammatory and stress-response modulation including NF-κB, cytokine signaling, HSPs, ER stress and adaptive antioxidant pathways.
  7. Migration, invasion, angiogenesis and tumor-microenvironment modulation; effects are field-parameter and tumor-model dependent.

Bioavailability / PK relevance: Conventional pharmacokinetic concepts do not apply because the intervention is a physical field rather than an absorbed drug. Relevant exposure variables are magnetic flux density, field gradient, frequency, waveform, pulse width, repetition rate, duty cycle, spatial distribution, treatment duration and tissue depth. Magnetic fields can penetrate tissue without the concentration gradients characteristic of drugs, but induced electric fields and biological coupling vary markedly with geometry and frequency.

In-vitro vs systemic exposure relevance: Effects are not concentration-driven. Many experimental results cannot be generalized between devices because apparently small differences in waveform, frequency, flux density, orientation, gradient and exposure duration can change the biological response. Static fields ranging from millitesla to tesla and PEMF/ELF protocols ranging from weak fields to substantially stronger stimulation should therefore be treated as distinct exposure regimens rather than as a single dose-response continuum.

Clinical evidence status: Cancer treatment remains predominantly preclinical, with cell-culture and animal evidence plus limited supportive or adjunctive human use. Evidence supports parameter-dependent anticancer effects and chemosensitization, but non-rotating magnetic-field exposure alone is not an established standard anticancer therapy. PEMF has established clinical use in several musculoskeletal applications and has been studied as supportive therapy in oncology. Repetitive transcranial magnetic stimulation has substantially stronger human evidence in neurological and psychiatric applications, including investigational use in Alzheimer’s disease, but should not be interpreted as evidence that generic magnetic-field exposure is an established systemic cancer treatment.

Magnetic Fields can be Static, or pulsed. The most common therapy is a pulsed magnetic field in the uT or mT range.
The main pathways affected are:
Calcium Signaling: -influence the activity of voltage-gated calcium channels.
Oxidative Stress and Reactive Oxygen Species (ROS) Pathways
Heat Shock Proteins (HSPs) and Cellular Stress Responses
Cell Proliferation and Growth Signaling: MAPK/ERK pathway.
Gene Expression and Epigenetic Modifications: NF-κB
Angiogenesis Pathways: VEGF (improving VEGF for normal cells)
PEMF was found to have a 2-fold increase in drug uptake compared to traditional electrochemotherapy in rat melanoma models

Pathways:
- most reports have ROS production increasing in cancer cells , while decreasing in normal cells.
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, 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 : NLRP3↓, IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, VEGF↓(mostly regulated up in normal cells),
- cause Cell cycle arrest : TumCCA↑,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓,
- inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, GLUT1↓, LDH↓, HK2↓, PFKs↓, PDKs↓, ECAR↓, OXPHOS↓, GRP78↑, Glucose↓, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, FGF↓, PDGF↓, EGFR↓, Integrins↓,
- Others: PI3K↓, AKT↓, STAT↓, Wnt↓, β-catenin↓, ERK↓, JNK, - SREBP (related to cholesterol).
- Synergies: chemo-sensitization, chemoProtective, cytoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

Magnetic Field Mechanisms in Cancer

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 ROS and redox homeostasis ↑ ROS (context-dependent); ↑ oxidative stress ↑ transient ROS followed by ↔ or ↓ ROS in adaptive protocols P, R, G Redox perturbation One of the most recurrent MF mechanisms. Direction is strongly field- and cell-dependent; sustained ROS elevation is reported in several cancer models and during chemotherapy sensitization.
2 Ca²⁺ and ion-channel signaling ↑ Ca²⁺ signaling or dysregulation; altered TRPC and voltage-sensitive channel activity ↑ transient signaling with homeostatic recovery (context-dependent) P, R Electrophysiological signal transduction Ca²⁺ is a major mechanistic bridge between membrane sensing, mitochondria, ROS, proliferation and apoptosis. Response depends strongly on waveform and frequency.
3 Mitochondrial function and membrane potential ↓ ΔΨm; altered respiration; ↑ mitochondrial stress ↔ or reversible modulation (context-dependent) P, R, G Bioenergetic destabilization Mitochondrial effects can arise downstream of ROS and Ca²⁺ signaling and contribute to apoptotic commitment.
4 Apoptosis and caspase signaling ↑ apoptosis; ↑ caspases; ↑ PARP cleavage; ↑ Bax; ↓ survivin ↔ or substantially weaker response in selective protocols R, G Programmed cell death Reported with several PEMF and time-varying field protocols and can be amplified when combined with chemotherapy.
5 EGFR PI3K AKT mTOR signaling ↓ EGFR/AKT/mTOR signaling (model-dependent) ↔ or mixed R, G Growth-signal suppression Particularly supported in static-field experiments; response varies with cell type, cell density and field intensity.
6 Cell cycle and proliferation ↓ proliferation; ↑ cell-cycle arrest or mitotic disruption ↔ or mixed G Growth suppression Effects are highly protocol-specific. Some exposures are neutral or can stimulate proliferation, so suppression should not be treated as universal.
7 DNA damage and DNA-damage response ↑ DNA damage; ↑ ATM/p53/p21 signaling (context-dependent) ↔ or mixed; protective responses reported with some protocols R, G Genotoxic stress and repair modulation Often secondary to ROS and particularly evident during combination treatment with chemotherapy or radiation. Magnetic fields alone are not consistently genotoxic, and some static-field protocols can reduce radiation-associated DNA damage.
8 Chemosensitization and drug uptake ↑ chemotherapy response; ↑ drug uptake or cytotoxicity ↔ or ↑ toxicity (drug-dependent) R, G Adjunctive anticancer effect Documented with doxorubicin, etoposide and other agents. Selectivity is not guaranteed; normal-cell toxicity must be evaluated for each field-drug combination.
9 Glutathione and antioxidant buffering ↓ GSH reserve or altered GSH/GSSG balance (context-dependent) ↑ GSH or antioxidant adaptation in some protocols R, G Redox buffering modulation GSH depletion is best interpreted as a consequence of oxidative load rather than a universal direct MF target.
10 NRF2 antioxidant response ↔ / mixed; inadequate adaptive response in some oxidative protocols ↑ NRF2 and antioxidant-response signaling in some protective protocols R, G Adaptive antioxidant defense NRF2 direction is not uniform enough to classify MF globally as either an NRF2 activator or inhibitor.
11 ER stress and unfolded protein response ↑ ER stress and UPR (model-dependent) ↑ adaptive stress response or ↔ R, G Proteostasis stress Can develop secondary to ROS, altered Ca²⁺ handling and mitochondrial dysfunction.
12 Mitochondrial permeability transition ↑ MPTP opening propensity ↔ or reversible opening R Mitochondrial death commitment Supported mechanistically for specific ELF-MF exposures through ROS-sensitive pathways; should not be generalized to all magnetic fields.
13 Glycolysis and cellular energetics ↓ glycolytic flux or altered ATP production (model-dependent) ↔ or metabolic adaptation R, G Metabolic reprogramming Some frequency-tuned exposures suppress glycolysis, but this is substantially less universal than ROS or Ca²⁺ modulation.
14 HIF-1α and angiogenic signaling ↓ HIF-1α / VEGF in selected models ↑ VEGF or tissue-repair signaling in some regenerative protocols G Angiogenesis modulation Potential cancer-versus-normal-tissue divergence is attractive but remains highly exposure- and model-specific.
15 NF-κB and inflammatory signaling ↓ NF-κB and inflammatory signaling in selected models ↓ inflammatory cytokines in many regenerative PEMF applications R, G Inflammation modulation Better established as an anti-inflammatory/regenerative PEMF effect than as a universal cancer-cell mechanism.
16 Migration invasion and angiogenesis ↓ migration; ↓ invasion; ↓ angiogenic signaling in selected models ↔ or pro-repair angiogenesis (context-dependent) G Metastatic phenotype modulation Direction varies substantially with field protocol and normal-versus-tumor context.
17 Radiosensitization ↑ radiation-induced ROS and DNA damage in selected protocols Mixed; radioprotection has also been reported with other protocols R, G Modification of radiation response Both radiosensitizing and radioprotective responses have been reported; field parameters and tissue context determine direction.
18 Clinical Translation Constraint Field-specific response; substantial tumor heterogeneity Potential tissue-specific physiological effects G Translation limitation No pharmacokinetic dose metric exists. Field strength, frequency, waveform, geometry, gradients, duration and induced electric fields must be specified. Most anticancer evidence remains preclinical and protocols are poorly standardized.

P: 0–30 min     R: 30 min–3 hr     G: >3 hr

MPTP: opening represents a mitochondrial commitment event integrating ROS and Ca²⁺ stress; sustained opening indicates irreversible bioenergetic failure.




Alzheimer’s disease relevance: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive magnetic neuromodulation modality with randomized human evidence for modest improvement in global cognition in mild cognitive impairment and Alzheimer’s disease. The strongest recent evidence supports excitatory stimulation of cortical cognitive-network regions, particularly the dorsolateral prefrontal cortex. The mechanism is principally neural-network and synaptic modulation rather than the systemic ROS-based mechanism often discussed for low-intensity PEMF. Meta-analyses generally report cognitive benefit, but protocol heterogeneity, small trials and uncertain durability remain important limitations. rTMS should therefore be classified as investigational or adjunctive for AD rather than an established disease-modifying treatment.

Clinical evidence status: Multiple RCTs and meta-analyses support a modest short-term cognitive signal. Longer-term benefit remains less certain, optimal frequency/intensity/site protocols are not standardized, and evidence does not establish prevention or reversal of Alzheimer pathology.

Magnetic Stimulation in Alzheimer’s Disease

Rank Pathway / Axis Modulation TSF Primary Effect Notes / Interpretation
1 Cortical network excitability ↑ P, R Neuromodulation High-frequency rTMS and excitatory stimulation of cortical network hubs can increase cortical responsiveness.
2 Synaptic plasticity ↑ R, G Plasticity enhancement Repeated stimulation can produce LTP-like network effects and is a leading explanation for persistence beyond the stimulation session.
3 Cognitive-network connectivity ↑ G Network normalization DLPFC and related cortical networks are the most consistently studied targets.
4 Global cognition ↑ G Clinical cognitive improvement Recent meta-analyses show modest improvement in MMSE, MoCA or ADAS-Cog outcomes, although heterogeneity remains substantial.
5 Neuroinflammation and neurotrophic signaling ↓ inflammation; ↑ neurotrophic signaling (context-dependent) G Secondary neurobiological effects Supported mainly by mechanistic and preclinical studies; less directly established than cortical-network effects in human AD.
6 Clinical Translation Constraint ↔ G Protocol heterogeneity Optimal stimulation site, frequency, intensity, pulse count, session number and maintenance schedule remain unresolved; long-term disease modification has not been demonstrated.

P: 0–30 min     R: 30 min–3 hr     G: >3 hr
JNK, c-Jun N-terminal kinase (JNK): Click to Expand ⟱
Source:
Type:
JNK acts synergistically with NF-κB, JAK/STAT, and other signaling molecules to exert a survival function. Janus signaling promotes cancer cell survival.
JNK, or c-Jun N-terminal kinase, is a member of the mitogen-activated protein kinase (MAPK) family. It plays a crucial role in various cellular processes, including cell proliferation, differentiation, and apoptosis (programmed cell death). JNK is activated in response to various stress signals, such as UV radiation, oxidative stress, and inflammatory cytokines.
JNK activation can promote apoptosis in cancer cells, acting as a tumor suppressor. However, in other contexts, it can promote cell survival and proliferation, contributing to tumor progression.

JNK is often unregulated in cancers, leading to increased cancer cell proliferation, survival, and resistance to apoptosis. This activation is typically associated with poor prognosis and aggressive tumor behavior.
Scientific Papers found: Click to Expand⟱
3457- MF,    Cellular stress response to extremely low‐frequency electromagnetic fields (ELF‐EMF): An explanation for controversial effects of ELF‐EMF on apoptosis
- Review, Var, NA
Apoptosis↑, Ding et al., 8 it was demonstrated that 24‐h exposure to 60 Hz, 5 mT ELF‐EMF could potentiate apoptosis induced by H2O2 in HL‐60 leukaemia cell lines.
H2O2↑,
ROS↑, One of the main mechanisms proposed for defining anticancer effects of ELF‐EMF is induction of apoptosis through upregulation of reactive oxygen species (ROS) which has also been confirmed by different experimental studies.
eff↑, intermittent 100 Hz, 0.7 mT EMF significantly enhanced rate of apoptosis in human hepatoma cell lines pretreated with low‐dose X‐ray radiation.
eff↑, 50 Hz, 45 ± 5 mT pulsed EMF, significantly potentiated rate of apoptosis induced by cyclophosphamide and colchicine
Ca+2↑, Over the past few years, lots of data have shown that ELF‐EMF exposure regulates intracellular Ca2+ level
MAPK↑, Mitogen‐activated protein kinase (MAPK) cascades are among the other important signalling cascades which are stimulated upon exposure to ELF‐EMF in several types of examined cells
*Catalase↑, ELF‐EMF exposure can upregulate expression of different antioxidant target genes including CAT, SOD1, SOD2, GPx1 and GPx4.
*SOD1↑,
*GPx1↑,
*GPx4↑,
*NRF2↑, Activation and upregulation of Nrf2 expression, the master redox‐sensing transcription factor may be the most prominent example in this regard which has been confirmed in a Huntington's disease‐like rat model.
TumAuto↑, Activation of autophagy, ER stress, heat‐shock response and sirtuin 3 expression are among the other identified cellular stress responses to ELF‐EMF exposure
ER Stress↑,
HSPs↑,
SIRT3↑,
ChemoSen↑, Contrarily, when chemotherapy and ELF‐EMF exposure are performed simultaneously, this increase in ROS levels potentiates the oxidative stress induced by chemotherapeutic agents
UPR↑, In consequence of ER stress, cells begin to initiate UPR to counteract stressful condition.
other↑, Since the only proven effects of ELF‐EMF exposure on cells are cellular adaptive responses, ROS overproduction and intracellular calcium overload
PI3K↓, figure 3
JNK↑,
p38↑,
eff↓, ontrarily, when cells are exposed to ELF‐EMF, a new source of ROS production is introduced in cells which can at least partially reverse anticancer effects observed with cell's treatment with melatonin.
*toxicity?, More importantly, ELF‐EMF exposure to normal cells in most cases has shown to be safe and un‐harmful.

486- MF,    mTOR Activation by PI3K/Akt and ERK Signaling in Short ELF-EMF Exposed Human Keratinocytes
- in-vitro, Nor, HaCaT
*mTOR↑,
*PI3K↑, HaCaT cells exposed for 1h to 50Hz/1mT showed an increased percentage of cells in the S phase, through a significantly activation of the PI3K, JNK and ERK pathways
*Akt↑,
*p‑ERK↑,
*other↑, increases in the percentage of cells in the S phase and decrease in the percentage of cells in G0/G1 phase
*p‑JNK↑,
*p‑P70S6K↑,

204- MFrot,  MF,    Rotating magnetic field improved cognitive and memory impairments in a sporadic ad model of mice by regulating microglial polarization
- in-vivo, AD, NA
*NF-kB↓, RMF improves memory and cognitive impairments in a sporadic AD model, potentially by promoting the M1 to M2 transition of microglial polarization through inhibition of the NF-кB/MAPK signaling pathway.
*MAPK↓,
*TLR4↓,
*memory↑,
*cognitive↑,
*TGF-β1↑, RMF treatment promoted the expression of anti-inflammatory cytokines (TGF-β1, Arg-1, IL-4, IL-10)
*ARG1/2↑, Arg-1
*IL4↑,
*IL10↑,
*IL6↓,
*IL1↓, IL-1β
*TNF-α↓,
*iNOS↓,
*ROS↓, in mice brain
*NO↓, in serum
*MyD88↓,
*p‑IKKα↓, phosphorylated IKKα/β, IкBα, NF-кB p65, JNK, p38,
*p‑IκB↓, IкBα
*p‑p65↓,
*p‑JNK↓,
*p‑p38↓,
*ERK↓,
*neuroP↑, RMF treatment resulted in reduced aluminum deposition in the brains of AD mice.
*Aβ↓, RMF treatment reduced Aβ deposition in the AD model mice

218- MFrot,  MF,    Extremely low frequency magnetic fields inhibit adipogenesis of human mesenchymal stem cells
- in-vitro, Nor, NA
*PPARγ↓, PPARg2
*p‑JNK↑, p-JNK
*Wnt↑,
*ALP∅, ELF-MF had no effects on the expression of ALP, COL1a1, Runx2, and OCN
*COL1∅,
*RUNX2∅,
*OCN∅,
*FABP4↓, ELF-MF exposure for 15 days resulted in a decrease in PPARg2 and FABP4
*p‑JNK↑, p-JNK was increased after ELF-MF exposure
*Diff↓, adipogenic differentiation of MSCs could be inhibited by ELF-MF of 7.5 Hz, 0.4 T, suggesting the inhibitory effect of ELF-MF on obesity may be attributed to the inhibition of differentiation of MSCs into adipocytes.


Showing Research Papers: 1 to 4 of 4

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 4

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

H2O2↑, 1,   ROS↑, 1,   SIRT3↑, 1,  

Cell Death(tgid=5) ⓘ

Apoptosis↑, 1,   JNK↑, 1,   MAPK↑, 1,   p38↑, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

other↑, 1,  

Protein Folding & ER Stress(tgid=8) ⓘ

ER Stress↑, 1,   HSPs↑, 1,   UPR↑, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

TumAuto↑, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

PI3K↓, 1,  

Migration(tgid=13) ⓘ

Ca+2↑, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

ChemoSen↑, 1,   eff↓, 1,   eff↑, 2,  
Total Targets: 17

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

Catalase↑, 1,   GPx1↑, 1,   GPx4↑, 1,   NRF2↑, 1,   ROS↓, 1,   SOD1↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

FABP4↓, 1,   PPARγ↓, 1,  

Cell Death(tgid=5) ⓘ

Akt↑, 1,   iNOS↓, 1,   p‑JNK↓, 1,   p‑JNK↑, 3,   MAPK↓, 1,   p‑p38↓, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

OCN∅, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

other↑, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

Diff↓, 1,   ERK↓, 1,   p‑ERK↑, 1,   mTOR↑, 1,   p‑P70S6K↑, 1,   PI3K↑, 1,   RUNX2∅, 1,   Wnt↑, 1,  

Migration(tgid=13) ⓘ

ARG1/2↑, 1,   COL1∅, 1,   TGF-β1↑, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

NO↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

p‑IKKα↓, 1,   IL1↓, 1,   IL10↑, 1,   IL4↑, 1,   IL6↓, 1,   p‑IκB↓, 1,   MyD88↓, 1,   NF-kB↓, 1,   p‑p65↓, 1,   TLR4↓, 1,   TNF-α↓, 1,  

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 1,  

Clinical Biomarkers(tgid=22) ⓘ

ALP∅, 1,   IL6↓, 1,  

Functional Outcomes(tgid=23) ⓘ

cognitive↑, 1,   memory↑, 1,   neuroP↑, 1,   toxicity?, 1,  
Total Targets: 46

Scientific Paper Hit Count for: JNK, c-Jun N-terminal kinase (JNK)
4 Magnetic Fields
2 Magnetic Field Rotating
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#:172  Target#:168  State#:%  Dir#:%
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