PEMF and breast cancer

Iversen JN, Tai YK, Yap JLY, Abdul Razar RBB, Sukumar VK, Wu KY, Ooi MG, Kukumberg M, Adam S, Rufaihah AJ, Franco-Obregón A. One Month of Brief Weekly Magnetic Field Therapy Enhances the Anticancer Potential of Female Human Sera: Randomized Double-Blind Pilot Study. Cells. 2025 Feb 23;14(5):331. PMC free paper

This study is based on the observation that those that engage in aerobic exercise are less likely to get breast cancer. Those that do, have better outcomes according to the literature review of Iverson 2025. The problem with all of this is that not everyone can exercise. What if application of PEMF to thigh muscles could release “myokines” that slow growth in a breast cancer cell line. This post provides background to the Iverson 2025 study. The HTRA1 and PEMF post examines background established in Tai 2024 published just one year prior!.

Fig 1 What was done

Serum is blood minus the cells and clotting factors. Serum contains hormone growth factors and nutrients. Biologists use serum when they grow cells in culture. Fetal calf serum is for cells in the growth phase. Adult horse serum might be used for the myoblast cell line C2C12 in the differentiated state. Could our own serum be anti-oncogentic?

See the above Fig 1 link for a flow chart of the study. basically 26 healthy females (ages 30–45) were assigned to either a magnetic therapy group, receiving twice weekly 1 mT magnetic exposures (10 min/session) for 4 weeks, or a control group, who underwent identical sham exposure. Blood sera were evaluated for their capacity to modulate breast cancer-related cellular responses and epithelial–mesenchymal transition. A few males received treatment or sham and donated serum for assays related to the MCF-7 breast cancer cell line and the C1C12 myoblast cell line.

Fig 2 some oncogenic tests

All cultured cells require serum, blood minus cells and clotting factors. The serum contains nutrients and growth factors. As mentioned in a previous post, MCF7 cells differ from the normal breast epithelial cells in that the chromosomal compartments containing Wnt pathway genes has undergone some opening.

• A DNA content, cancer cells Week 8 female volunteer serum gained the ability to decrease the DNA content of MCF7 cells. Cell viability was also by 8week control vs PEMF female serum.
• B None one of the 1c3, 8 week time point sera from the male volunteers had any effect on the DNA content of MCF07 cells. Male serum did little that panned out statistically.
• C an invasion of agar test The triple negative MDA-MB-231 breast cancer cells 48 h following treatment with female sera at the 1 , 5, and 8 week treatment time points. PEMF treatments are cumulative in that 8 week serum leads to less invasion than 1 week serum. PEMF 8 week serum led to less invasion that sham serum after 8 weeks.
• D the scratch test MCF-7 cell line is an estrogen receptor-positive (ER+), progesterone receptor-positive (PR+) and HER2-negative (HER2-) breast cancer cell model representative of a luminal subtype of breast cancer that exhibits the ability to proliferate and form monolayers. This assay is pretty simple: Grow cells in a monolayer, scratch a big gap in the monolayer, and watch the cells grow back. Sera from PEMF treated women
• E DNA content, normal cells The sera from PEMF treated females did not change the DNA content of C2C12 myoblasts or the normal breast epithelial cell line MCF10. This suggests the PEMF treatment will not release compounds into the blood stream that will change the DNA content of normal cells.

The epithelial-mesenchymal transition, prelude to Fig 3

Much of Iverson2025 looks at this common cancer pathway.

Note that TGFβ is one of the inducers.

Fig 3 the Transforming Growth Factor β, TGFβ, pathway

The TGFβ pathway is anything but simple. There are receptor subtypes I, II, and III that work together to bind TGFβ. After this event kinase regions auto phosphorylate. In the canonical pathway SMADs

The intermediate filament vimentin is not in the above cartoon. Wikipedia authors write of its role in maintaining cell shape, linking mitochondria, the nucleus and endoplasmic reticulum. It is linked to EMT.

• panel h is a very similar cartoon to this one but is not being used because of a likely copyright. The SMADs get phosphorylated by the TGFβ, receptor, a receptor tyrosine kinase. SMADs are transcription factors. Iverson 2025 brings in Slug to join Twist and Snail transcription factors.
• panel a The TGFβ receptor transcripts, control vs PEMF, decreased with serum from 8 weeks of PEMF treatment females.
• panel b The twist transcription factor, using week 1 serum as a bench mark, was less when breast cancer cells were grown in serum from PEMF treated women for five and eight weeks. These levels are protein levels. A decrease can be to moreproduction or less degradation.
• panel c and d Snail and Slug transcription factor protein levels decreased when the MCF7 cells were grown serum from women treated with PEMF for eight weeks.
• panel e There’s a slight decrease in β-catenin in response to the 8 PEMF week sera. Phosphorylation targets β-catenin for degradation.
• panel f Vimentin was less with 8 week PEMFtreatment sera.

Fig 4 angiogenic factors

Fig 4 covers angiogenic factors. The trend is for PEMF to cause serum angiogenic factors was to go down or to not change. These changes were statistically significant but generally not very large in magnitude, except Vascular Endothelial Growth Factor A (VEGFA)is a contributor to angiogenesis

Fig 5, myokines using a commercial kit

Iverson 2025 found a commercial kit for measuring protein levels of these so called myokines in biological fluids. Many of these “myokines” that changed in response to PEMF, are also adipokines. It is the female thigh that is a reserve of fat. I made a short video putting some of the significant changes in perspective of the published literature.

Not all of the four significant changes in a very targeted population of “myokines” point towards treating breast cancer. It should be remembered that these same sera inhibit cell culture model of carcinogenesis.

aa independent look at TGFβ and Wnt

To be honest, Iverson 2025 did not even look at the Wnt pathways covered in the Wnt and cancer post that explored the differences between MCF7 (carcinogenic) and MCF10 (normal) breast cells. To be honest, there is not a lot of evidence in the literature to justify measuring Wnt isoforms that might have been secreted by adipocytes and/or myocytes in the volunteers.

The TGFβ receptor, a tyrosine kinase receptor TKR, or tyrosine kinase receptor. Note that many of the transcription factors in this cartoon obtained from Wikimedia Commons were also addressed by Iverson 2025.

Schematic representation of cell signaling pathways involved in autophagy and epithelial-mesenchymal-transition (EMT).The following text was associated with the Wikimedia Commons image.

1. In the canonical WNT signaling, β-catenin stabilizes and translocates to the nucleus after binding of WNT to Frizzled and low-density lipoprotein receptor-related protein 5/6 (LRP5/6) receptors. GSK3 is sequestered together with proteins of the destruction complex of β-catenin (DVL, axin, CK1).
2. In the nucleus, β-catenin binds to TCF/LEF transcriptional factors, activating its target genes. β-catenin also stimulates transcription of important EMT transcriptional factors such as ZEB1/ZEB2, Twist and Snail/slug. ZEB1 and Twist may be involved with breast cancer.
3. EMT is also induced by the mammalian Target of Rapamycin Complex 1 (mTORC1) signaling, through activation of the transcriptional factors ZEB1/ZEB2, Twist and Snail/Slug. mTORC1 and mTORC2 are activated by tyrosine kinase receptor (TKR) signaling through PI3K/AKT. mTORC2 also stimulates AKT. Fig 4 of Iverson 2025 shows mostly decreases in serum content of angiogenic factors Angiopoietin-2, BMP-9, Endoglin, PLGF, VEGF-A, , most of which bind to receptor tyrosine kinases. Leptin was increased in the 5-8 week window.
4. Depending on the energy status of the cell, activation of AMP Kinase (AMPK) inhibits mTORC1 and induces macroautophagy (MA).
5. Chaperone-mediated autophagy (CMA) degrades cytosolic proteins that possess the KFERQ or KFERQ-like motif through recognition and binding of the heat shock-cognate chaperone of 71 kDa (HSC70) and a cochaperone complex. HSC70 targets the substrate protein to the lysosomal membrane, where it binds monomeric lysosome-associated membrane protein type 2A (LAMP2A) and induces its multimerization and stabilization. The substrate protein is unfolded and translocated into the lysosome for degradation through multimerized LAMP2A.
6. In mammals, microautophagy (mA) occurs in the late endosome, in a process called endosomal microautophagy. It can degrade cytosolic proteins, and some are recognized by HSC70. Some proteins, such as GSK3, are targeted for mA through arginine methylation (meArg) by protein arginine methyltransferases (PRMTs). After entering the late endosome, this organelle fuses with lysosomes to complete the mA cycle.
7. In the noncanonical WNT signaling, WNTs bind to Frizzled receptors and DVL1 is recruited to the membrane. c-Jun N-terminal kinases (JNKs), RhoA and phosphoinositide phospholipase C (PLC) can be activated by noncanonical WNT. JNK and RhoA further regulate the cytoskeleton, and JNK induces gene transcription through activator protein 1 (AP1). PLC increases cytosolic Ca²⁺ levels, leading to activation of Ca²⁺/calmodulin-dependent protein kinase II (CAM-KII) and calcineurin, which activate nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nuclear factor of activated T cells (NFAT), respectively. Solid black lines represent activation, while solid red lines represent inhibition. Double black lines represent indirect activation. Dashed lines indicate protein interactions when the WNT/β-catenin and mTOR signaling are not activated.

the endocannabionoid factor

Running releases endocannabinoids. This is a personal favorite of my that would have been grossly impractical for Iverson 2025 to address. If PEMF is like exercise and releases endocannabinoids from muscle, they could potentially be part of the process.

Matei D, Trofin D, Iordan DA, Onu I, Condurache I, Ionite C, Buculei I. The Endocannabinoid System and Physical Exercise. Int J Mol Sci. 2023 Jan 19;24(3):1989. PEMF free paper

This is a really nice review on, as the name suggests, exercise and the endocannabinoid system. Fig 1 describes the location of cannabinoid 1 and 2 receptors. Fig 2 lists the positive effects of exercise. Fig 3 links positive effects of exercise to organ specific aspects of the endocannabinoid system. increased adiponectin from adipocytes.

Akimov MG, Gretskaya NM, Gorbacheva EI, Khadour N, Chernavskaya VS, Sherstyanykh GD, Kovaleko TF, Fomina-Ageeva EV, Bezuglov VV. The Interaction of the Endocannabinoid Anandamide and Paracannabinoid Lysophosphatidylinositol during Cell Death Induction in Human Breast Cancer Cells. Int J Mol Sci. 2024 Feb 14;25(4):2271. PMC free paper

Extracellular vesicles, PEMF, cancer, and exercise

QuantumTx has shown their technology promotes the release of extracellular vesicles from muscle cells.

Wong CJK, Tai YK, Yap JLY, Fong CHH, Loo LSW, Kukumberg M, Fröhlich J, Zhang S, Li JZ, Wang JW, Rufaihah AJ, Franco-Obregón A. Brief exposure to directionally-specific pulsed electromagnetic fields stimulates extracellular vesicle release and is antagonized by streptomycin: A potential regenerative medicine and food industry paradigm. Biomaterials. 2022 Aug;287:121658. free paper

What is the link between exercise, EV release, and cancer prevention?

Llorente A, Brokāne A, Mlynska A, Puurand M, Sagini K, Folkmane S, Hjorth M, Martin-Gracia B, Romero S, Skorinkina D, Čampa M, Cešeiko R, Romanchikova N, Kļaviņa A, Käämbre T, Linē A. From sweat to hope: The role of exercise-induced extracellular vesicles in cancer prevention and treatment. J Extracell Vesicles. 2024 Aug;13(8):e12500. PMC free paper

This review covers several triggers for ecercise induced EV release

1. mechanical stress
2. acidosis
3. small amounts of reactive oxygen species
4. increased intracellular Ca²⁺

All but the first two have been established to occur with QuantumTx PEMF treated muscle cells. Fig 1 of the Llorente 2024 has a cartoon of the process. Fig 2 of the Llorente 2024 review stresses that EV can come from multiple cell types and may have cargos other than micro RNA. The gender may make a difference, as per Iverson 2025. The Lolorente 2024 also mentions the angiogenic switch. Much of the discussion in this review covered micro RNA but left the impression that though a lot of research as been done, much is left unkown.

Concluding thoughts

The use of actual human sera for cell culture assays yielded encouraging results. Pinning those encouraging results to changes in protein factors is a bit difficult. QuantumTx seems to have a history with extracellular vesicle release in response to PEMF. In a previous job I extracted miRNA from serum and subjected it to high throughput miRNA array analysis with a company HTG Diagnostics. Characterization of the contents of EVs released from actual human volunteers or cultured cells could be interesting.