Magnetic fields modulate metabolism and gut microbiome in correlation with
            <i>Pgc‐1α</i>
            expression: Follow‐up to an in vitro magnetic mitohormetic study

Tai, Yee Kit; Ng, Charmaine; Purnamawati, Kristy; Yap, Jasmine Lye Yee; Yin, Jocelyn Naixin; Wong, Craig Jun Kit; Patel, Bharati; Soong, Poh Loong; Pelczar, Pawel; Fröhlich, Jürg; Beyer, Christian; Fong, Charlene Hui Hua; Ramanan, S.V.; Casarosa, Marco; Cerrato, Carmine Pasquale; Foo, Zi Ling; Selvan, Rina Malathi Pannir; Grishina, Elina; Degirmenci, Ufuk; Toh, Shi Jie; Richards, Pete J.; Mirsaidi, Ali; Wuertz‐Kozak, Karin; Chong, Suet Yen; Ferguson, Stephen J.; Aguzzi, Adriano; Monici, Monica; Sun, Li; Drum, Chester L.; Wang, Jiong‐Wei; Franco‐Obregón, Alfredo

doi:10.1096/fj.201903005rr

Cited by 21 publications

(30 citation statements)

References 119 publications

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“…TRPC1 is a mitohormetic determinant governing cellular inflammatory status and survival ( 5 , 6 , 11 ). Elevated TRPC1 expression defines numerous types of cancers ( 15 , 37 ).…”

Section: Discussionmentioning

confidence: 99%

“…Brief exposure (10 min) to low amplitude (1 mT) pulsing magnetic fields (PEMFs) has been shown capable of stimulating mitochondrial respiration and ROS production ( 5 ), thereby promoting both in vitro ( 5 ) and in vivo ( 6 ) myogeneses via a process of Magnetic Mitohormesis. Obeying a mitohormetic mechanism of operation ( 7 ), brief and low amplitude PEMF exposure would produce sufficiently low levels of ROS to instill mitochondrial survival adaptations, whereas exaggerated PEMF exposure might be expected to produce detrimental oxidative stress that would instead stymie cell survival.…”

Section: Introductionmentioning

confidence: 99%

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Modulated TRPC1 Expression Predicts Sensitivity of Breast Cancer to Doxorubicin and Magnetic Field Therapy: Segue Towards a Precision Medicine Approach

et al. 2022

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Chemotherapy is the mainstream treatment modality for invasive breast cancer. Unfortunately, chemotherapy-associated adverse events can result in early termination of treatment. Paradoxical effects of chemotherapy are also sometimes observed, whereby prolonged exposure to high doses of chemotherapeutic agents results in malignant states resistant to chemotherapy. In this study, potential synergism between doxorubicin (DOX) and pulsed electromagnetic field (PEMF) therapy was investigated in: 1) MCF-7 and MDA-MB-231 cells in vitro; 2) MCF-7 tumors implanted onto a chicken chorioallantoic membrane (CAM) and; 3) human patient-derived and MCF-7 and MDA-MB-231 breast cancer xenografts implanted into NOD-SCID gamma (NSG) mice. In vivo, synergism was observed in patient-derived and breast cancer cell line xenograft mouse models, wherein PEMF exposure and DOX administration individually reduced tumor size and increased apoptosis and could be augmented by combined treatments. In the CAM xenograft model, DOX and PEMF exposure also synergistically reduced tumor size as well as reduced Transient Receptor Potential Canonical 1 (TRPC1) channel expression. In vitro, PEMF exposure alone impaired the survival of MCF-7 and MDA-MB-231 cells, but not that of non-malignant MCF10A breast cells; the selective vulnerability of breast cancer cells to PEMF exposure was corroborated in human tumor biopsy samples. Stable overexpression of TRPC1 enhanced the vulnerability of MCF-7 cells to both DOX and PEMF exposure and promoted proliferation, whereas TRPC1 genetic silencing reduced sensitivity to both DOX and PEMF treatments and mitigated proliferation. Chronic exposure to DOX depressed TRPC1 expression, proliferation, and responses to both PEMF exposure and DOX in a manner that was reversible upon removal of DOX. TRPC1 channel overexpression and silencing positively correlated with markers of epithelial-mesenchymal transition (EMT), including SLUG, SNAIL, VIMENTIN, and E-CADHERIN, indicating increased and decreased EMT, respectively. Finally, PEMF exposure was shown to attenuate the invasiveness of MCF-7 cells in correlation with TRPC1 expression. We thus demonstrate that the expression levels of TRPC1 consistently predicted breast cancer sensitivity to DOX and PEMF interventions and positively correlated to EMT status, providing an initial rationale for the use of PEMF-based therapies as an adjuvant to DOX chemotherapy for the treatment of breast cancers characterized by elevated TRPC1 expression levels.

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“…TRPC1 is a mitohormetic determinant governing cellular inflammatory status and survival ( 5 , 6 , 11 ). Elevated TRPC1 expression defines numerous types of cancers ( 15 , 37 ).…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Modulated TRPC1 Expression Predicts Sensitivity of Breast Cancer to Doxorubicin and Magnetic Field Therapy: Segue Towards a Precision Medicine Approach

et al. 2022

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“…TRPC1 is a mitohormetic determinant governing cellular inflammatory status and survival (5,6,9), whose elevated expression defines numerous cancers (13,50). We demonstrate that the vulnerability of breast cancer to PEMF and DOX therapies is correlated with TRPC1 expression, conferring a heightened level of specificity for such TRPC1-characterized cancers (Fig.…”

Section: Discussionmentioning

confidence: 68%

“…Brief exposure (10 min) to low amplitude (1 mT) pulsing magnetic fields (PEMFs) has been shown capable of stimulating mitochondrial respiration and ROS production (5), thereby promoting both in vitro (5) and in vivo (6) myogeneses via a process of magnetic mitohormesis. Obeying a mitohormetic mechanism of operation (7), brief and low amplitude PEMF exposure would produce low levels of ROS sufficient to instill mitochondrial survival adaptations, whereas exaggerated PEMF exposure might be expected to produce detrimental levels of oxidative stress that instead stymie cell survival.…”

Section: Introductionmentioning

confidence: 99%

Modulated TRPC1 expression predicts sensitivity of breast cancer to doxorubicin and magnetic field therapy: segue towards a precision medicine approach

Tai

Fong

et al. 2021

Preprint

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BackgroundChemotherapy is the mainstream treatment modality for invasive breast cancer. Nonetheless, chemotherapy-associated adverse events can result in a patient terminating treatment. We show that transient receptor potential channel 1 (TRPC1) expression level predicts breast cancer sensitivity to doxorubicin (DOX) and pulsed electromagnetic field (PEMF) therapies.MethodsThe effects of PEMFs were examined with respect to: 1) the growth of MCF-7 cells in vitro; 2) MCF-7 tumors implanted into a chicken chorioallantoic membrane (CAM) model and; 3) patient-derived and MCF-7 breast cancer xenografts in mice.Potential synergisms between DOX and PEMF therapies were examined in these model systems and under conditions of TRPC1 overexpression or silencing in vitro.ResultsPEMF exposure impaired the survival of MCF-7 cells, but not that of nonmalignant MCF10A breast cells. The effects of PEMF- and DOX-therapies synergized in vitro at compromising MCF-7 cell growth. Synergism could be corroborated in vivo with patient-derived xenograft mouse models, wherein PEMF exposure alone or in combination with DOX reduced tumor size. Stable overexpression of TRPC1 enhanced the vulnerability of MCF-7 cells to both DOX and PEMF exposure and promoted proliferation, whereas chronic DOX exposure reduced TRPC1 expression, induced chemoresistance, precluded response to PEMF exposure and mitigated proliferation. Markers of metastasis including SLUG, SNAIL, VIMENTIN, and E-CADHERIN as well as invasiveness were also positively correlated with TRPC1 channel expression.ConclusionThe presented data supports a potential role of PEMF-therapy as an effective companion therapy to DOX-based chemotherapy for the treatment of breast cancers characterized by elevated TRPC1 expression levels.

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“…Among other hypotheses, it is suggested that electromagnetic stimuli interact with cells via either ion channels or transmembrane receptors, thereby initiating signal transduction cascades or modifying cellular functions [ 5 , 36 ]. Brief exposure to low millitesla-range PEMF was recently shown to enhance mitochondriogenesis [ 37 ] and modulate metabolism and gut microbiome [ 38 ] in a cell study and animal experiment. The gut microbiome–immune system–brain axis is, in turn, sensitive to stress and plays an important role in the development of stress-related symptoms such as a major depressive disorder [ 39 ], which might explain the benefit of the PEMF application on certain psychological parameters.…”

Section: Discussionmentioning

confidence: 99%

Successful application of pulsed electromagnetic fields in a patient with post-COVID-19 fatigue: a case report

Wagner

Steiner

Markovic

et al. 2022

Wien Med Wochenschr

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Summary Background Post-COVID-19 fatigue is a frequent symptom in COVID-19 survivors, which substantially limits patients to achieve full recovery and potentially restrains return to work. The previous literature has not yet reported the use of pulsed electromagnetic fields in this indication. Methods Over the course of 5 weeks, 10 sessions of pulsed electromagnetic field treatment with a high magnetic flux density were applied to a patient suffering from post-COVID-19 fatigue syndrome. Fatigue, work ability, quality of life as well as anxiety, depression, stress level, and resilience were evaluated using validated patient-reported outcome measures. Results Fatigue, work ability, quality of life, and psychological well-being improved clearly over the course of the treatment and showed stable results 6 weeks later. Conclusion The use of pulsed electromagnetic field therapy with a device that allows sufficient penetration of the body tissue might be a promising physical modality to manage post-COVID-19 fatigue syndrome, which could reduce clinical and economic health consequences. Clinical sham-controlled studies are needed to evaluate the effect of pulsed electromagnetic fields in this indication.

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Magnetic fields modulate metabolism and gut microbiome in correlation with Pgc‐1α expression: Follow‐up to an in vitro magnetic mitohormetic study

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 21 publications

References 119 publications

Modulated TRPC1 Expression Predicts Sensitivity of Breast Cancer to Doxorubicin and Magnetic Field Therapy: Segue Towards a Precision Medicine Approach

Modulated TRPC1 Expression Predicts Sensitivity of Breast Cancer to Doxorubicin and Magnetic Field Therapy: Segue Towards a Precision Medicine Approach

Modulated TRPC1 expression predicts sensitivity of breast cancer to doxorubicin and magnetic field therapy: segue towards a precision medicine approach

Successful application of pulsed electromagnetic fields in a patient with post-COVID-19 fatigue: a case report

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