The cancer-fighting potential of muscles has taken a major step forward with the discovery of a new method that uses low-amplitude, low-frequency pulsed magnetic fields (PEMF) to safely stimulate muscle cells. This novel approach aims to harness the natural secretions of muscle cells, which have been found to contain potent anti-cancer properties. By harnessing these secretions, researchers hope to develop a noninvasive strategy to reduce the growth and invasiveness of cancer cells, particularly in breast cancer.
This pioneering research, led by Professor Alfredo Franco-Obregón and Dr. Yee Kit Tai of the National University of Singapore, was published in the open access journal CellsThe research team demonstrated that a single 10-minute exposure to low-energy PEMF could induce muscle cells to release a secretome with potent anticancer properties. The study further highlights the critical role of the protein High-Temperature Requirement A1 (HTRA1), which was shown to be necessary and sufficient for the observed anticancer effects. “The secretome’s ability to suppress tumor growth and vascularization was markedly enhanced by magnetic stimulation of the muscle cells that donated the secretome,” noted Professor Franco-Obregón.
In experiments, conditioned media from muscle cells exposed to PEMF reduced the proliferation and invasion of several breast cancer cell lines, including the more malignant human breast cancer cell lines MCF-7 and MDA-MB-231. When administered to breast cancer microtumors implanted in the chorioallantoic membrane of chicken eggs, PEMF-conditioned media significantly reduced the size of the microtumors and reduced the formation of new blood vessels that would otherwise support tumor growth. Dr. Tai explained, “Our results indicate that the secretome produced by magnetically stimulated muscle cells can effectively target and decrease the growth and spread of cancer cells.”
A surprising aspect of this study is the adaptability and increased potency of the secretome after repeated exposure to PEMF. By preconditioning muscle cells in tissue culture with PEMF-generated pCM, the researchers were able to stimulate the production of the muscle cell anti-cancer secretome response. in vitro and live“This preconditioning paradigm shows a new in vitro “A methodology has been developed to recreate the way exercise adapts skeletal muscles to constitutively produce anti-cancer factors, but now in isolated cultured muscle cells for clean purification of the generated anti-cancer factors for therapeutic exploitation. Furthermore, when our magnetic therapeutic platform is employed in the context of a person with cancer, it can amplify the body’s natural anti-cancer defenses, similar to exercise, but without the need for strenuous exercise, which may not be feasible for many cancer patients,” added Professor Franco-Obregón.
He BICEPS Laboratory The research team also explored the underlying mechanisms responsible for the observed anti-cancer effects. They identified HTRA1 as a key player in mediating these effects, as its upregulation in pCM was essential for reducing cancer cell viability. The study further demonstrated that recombinant HTRA1 could mimic the anti-cancer properties of pCM, while removal of HTRA1 from PEMF-conditioned medium abolished these effects. “The role of HTRA1 in this process is crucial and highlights its potential as a therapeutic target,” commented Dr. Tai.
These provocative in vitro and ex vivo The results were validated in mice that had either exercised (twice a week) or received magnetic stimulation (once a week for 10 minutes) for 8 weeks. Blood from both groups of mice was shown to inhibit breast cancer cell growth and invasion, and also showed elevated levels of HTRA1 relative to control mice that had neither exercised nor received magnetic therapy.
The implications of this research are truly profound and offer a promising non-invasive strategy to harness the muscle secretome in cancer therapy. The findings could pave the way for new clinical applications, particularly for patients who are unable to engage in regular physical exercise. Professor Franco-Obregón concluded: “Our study opens up new avenues for cancer treatment by safely releasing and utilizing natural bioactive agents released by muscle cells, providing a novel approach to cancer prevention and treatment.”
Journal reference
Tai, YK, Iversen, JN, Chan, KKW, Fong, CHH, Abdul Razar, RB, Ramanan, S., Yap, LYJ, Yin, JN, Toh, SJ, Wong, CJK, Koh PEA, Huang RYJ, Franco-Obregón A (2024). Magnetically stimulated muscle secretome exhibits anticancer potency: novel preconditioning methodology highlighting HTRA1 action. Cells, 13, 460. DOI: https://doi.org/10.3390/cells13050460
Wong CJK, Tai YK, Jasmine Lye Yee Yap, Fong CHH, Loo LSW, Kukumberg M, Fröhlich J, Zhang S, Jing Ze Li, Wang JW, Rufaihah AJ, Franco-Obregón A (2022). Brief exposure to directionally specific pulsed electromagnetic fields stimulates extracellular vesicle release and is antagonized by streptomycin: a potential paradigm for regenerative medicine and the food industry. Biomaterials, 287, 121658. DOI: https://doi.org/10.1016/j.biomaterials.2022.121658
About the authors
Associated Professor Alfredo Franco Obregon Professor Alfredo Franco-Obregón approaches tissue engineering and regeneration from a biophysical perspective, as an alternative to conventional pharmacological interventions. He is particularly interested in how electromagnetic and mechanical forces drive tissue regeneration. BICEPS Laboratory (Bioionic Currents Electromagnetic Pulse Systems) under the combined auspices of the Department of Surgery and iHealthtech (Institute of Health Innovation and Technology) at the National University of Singapore (NUS) and is actively investigating how magnetic fields promote mitochondrial respiration and subsequent developmental and survival adaptations through a process known as magnetic mitohormesis. His main areas of interest are skeletal muscle development, stem cell biology and cancer and he is a thought leader and innovator in the application of electromagnetic and mechanical forces for tissue engineering and regenerative medicine, clinical applications related to human health and longevity as well as sustainable food production.
National University of Singapore Profile: https://discovery.nus.edu.sg/4445-alfredo-francoobregon/about
Dr. Tai Yee's Kit He obtained his PhD from the National University of Singapore (NUS). In 2016 he joined the BICEPS Laboratory As a lead scientist, in collaboration with a team of expert scientists, Dr. Tai has been instrumental in the development and validation of cutting-edge magnetic devices designed to activate skeletal muscle. This pioneering research has demonstrated the mobilization of beneficial muscle factors, significantly advancing our understanding of muscle physiology and therapy. Furthermore, Dr. Tai’s work has revealed the remarkable efficacy of electromagnetic fields in stimulating a specific class of cation channels and thus presents a transformative opportunity to target cancer types marked by overexpression of these magnetic field-sensitive channels. This discovery has the potential to revolutionize cancer treatment and offer new avenues for targeted therapies. Dr. Tai’s contributions to electromagnetics, cancer, and regenerative medicine highlight his dedication to advancing medical innovation and commitment to improving patient care.
National University of Singapore Profile: https://discovery.nus.edu.sg/9228-yee-kit-alex-tai/about
Learn more about the BICEPS (Bio-Current Electromagnetic Pulse Systems) lab here: https://medicine.nus.edu.sg/biceps-lab/
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