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
Inflam">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
Non-Static Magnetic Fields (AC / Pulsed / Oscillating MF)
| Rank |
Pathway / Axis |
Cancer Cells |
Normal Cells |
TSF |
Primary Effect |
Notes / Interpretation |
| 1 |
Reactive oxygen species (ROS) |
↑ ROS (P→R); often sustained (G) |
↑ ROS (P); ↔/↓ net ROS (R→G) |
P, R, G |
Upstream redox perturbation |
MF perturbs electron/radical dynamics: normal cells often adapt (ROS setpoint ↓), cancer cells less so |
| 2 |
NRF2 antioxidant response |
↔ / insufficient NRF2 induction (R→G) |
↑ NRF2 activation (R→G) |
R, G |
Adaptive redox defense |
Explains mixed ROS direction in normal cells (initial ↑ then adaptive ↓) |
| 3 |
Glutathione (GSH) homeostasis |
↓ GSH (R→G) |
↔ or transient ↓ (R) with recovery (G) |
R, G |
Redox buffering capacity |
GSH depletion reflects sustained oxidative load; recovery indicates successful adaptation |
| 4 |
Superoxide dismutase (SOD) / antioxidant enzymes |
↔ or inadequate enzyme upshift (G) |
↑ SOD/GPx/CAT capacity (G) |
G |
Longer-term antioxidant remodeling |
Often the “endpoint” readout that correlates with ROS-normalization in normal tissue |
| 5 |
Mitochondrial ETC / respiration |
↓ ETC efficiency; ↑ electron leak (P→R) |
↔ mild, reversible ETC perturbation (P→R) |
P, R |
Bioenergetic destabilization |
ETC perturbation is a mechanistic bridge between MF exposure and ROS/ΔΨm changes |
| 6 |
Mitochondrial membrane potential (ΔΨm / MMP) |
↓ ΔΨm (R); may progress (G) |
↔ preserved or reversible dip (R) |
R, G |
Mitochondrial dysfunction thresholding |
ΔΨm loss typically follows ROS/ETC disruption rather than preceding it |
| 7 |
Ca²⁺ signaling (VGCC / ER–mitochondria Ca²⁺ flux) |
↑ dysregulated Ca²⁺ influx/transfer (P→R); overload may persist (G) |
↑ transient Ca²⁺ signaling (P); homeostasis restored (R→G) |
P, R, G |
Stress signal amplification |
Ca²⁺ dysregulation links ROS/ETC perturbation to ER stress and mitochondrial dysfunction (amplifies ΔΨm loss and UPR commitment) |
| 8 |
Mitochondrial permeability transition pore (MPTP) |
↑ MPTP opening propensity (R); sustained opening possible (G) |
↔ transient or closed (R→G) |
P, R, G |
Commitment point for mitochondrial failure |
MPTP opening integrates ROS, Ca²⁺ overload, and ΔΨm loss; acts as a threshold event converting reversible stress into irreversible mitochondrial dysfunction |
| 9 |
ER stress / UPR |
↑ ER stress (R); CHOP-commitment possible (G) |
↑ adaptive UPR (R); resolves (G) |
R, G |
Proteostasis stress |
Often downstream of ROS + Ca²⁺ handling perturbations |
| 10 |
DNA damage (oxidative) |
↑ damage markers (R→G) |
↔ or repaired (G) |
R, G |
Checkpoint pressure |
Generally secondary to ROS; interpret as stress consequence not “direct genotoxicity” |
| 11 |
LDH / glycolytic flux |
↓ glycolytic performance (R→G) |
↔ flexible substrate switching (R→G) |
R, G |
Metabolic vulnerability |
Redox imbalance can destabilize high-rate glycolysis in cancer-biased contexts |
| 12 |
Thioredoxin system (Trx / TrxR) |
↓ functional reserve / overload (R→G) |
↔ preserved capacity (G) |
R, G |
Parallel antioxidant system stress |
Useful when GSH-only does not explain redox phenotype |
Time-Scale Flag: TSF = P / R / G
P: 0–30 min (physical / electron / radical effects)
R: 30 min–3 hr (redox signaling & stress response)
G: >3 hr (gene-regulatory adaptation)
MPTP: opening represents a mitochondrial commitment event integrating ROS and Ca²⁺ stress; sustained opening indicates irreversible bioenergetic failure.
|