NMR exposure sensitizes tumor cells to apoptosis
NMR technology has dramatically contributed to the revolution of image diagnostic. NMR apparatuses use combinations of microwaves over a homogeneous strong (1 Tesla) static magnetic field. We had previously shown that low intensity (0.3–66 mT) static magnetic fields deeply affect apoptosis in a Ca2+ dependent fashion (Fanelli et al., 1999 FASEBJ., 13;95–102). The rationale of the present study is to examine whether exposure to the static magnetic fields of NMR can affect apoptosis induced on reporter tumor cells of haematopoietic origin. The impressive result was the strong increase (1.8–2.5 fold) of damage-induced apoptosis by NMR. This potentiation is due to cytosolic Ca2+ overload consequent to NMR-promoted Ca2+ influx, since it is prevented by intracellular (BAPTA-AM) and extracellular (EGTA) Ca2+ chelation or by inhibition of plasma membrane L-type Ca2+ channels. Three-days follow up of treated cultures shows that NMR decrease long term cell survival, thus increasing the efficiency of cytocidal treatments. Importantly, mononuclear white blood cells are not sensitised to apoptosis by NMR, showing that NMR may increase the differential cytotoxicity of antitumor drugs on tumor vs normal cells. This strong, differential potentiating effect of NMR on tumor cell apoptosis may have important implications, being in fact a possible adjuvant for antitumor therapies.
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Effects of Pulsed Magnetic Stimulation onTumor Development and Immune Functions in Mice
We investigated the effects of pulsed magnetic stimulation on tumor development processes and immune functions in mice. A circular coil (inner diameter¼15 mm, outer diameter¼75 mm) was used in the experiments. Stimulus conditions were pulse width¼238 ms, peak magnetic field¼0.25 T
(at the center of the coil), frequency¼25 pulses/s, 1000 pulses/sample/day and magnetically induced eddy currents in mice¼0.79–1.54 A/m2. In an animal study, B16-BL6 melanoma model mice were exposed to the pulsed magnetic stimulation for 16 days from the day of injection of cancer cells. A tumor growth study revealed a significant tumor weight decrease in the stimulated group (54%
of the sham group). In a cellular study, B16-BL6 cells were also exposed to the magnetic field (1000 pulses/sample, and eddy currents at the bottom of the dish¼2.36–2.90 A/m2); however, the magnetically induced eddy currents had no effect on cell viabilities. Cytokine production in mouse spleens was measured to analyze the immunomodulatory effect after the pulsed magnetic stimulation.
Tumor necrosis factor (TNF-a) production in mouse spleens was significantly activated after the exposure of the stimulus condition described above. These results showed the first evidence of the antitumor effect and immunomodulatory effects brought about by the application of repetitive magnetic stimulation and also suggested the possible relationship between anti-tumor effects and the increase of TNF-a levels caused by pulsed magnetic stimulation.
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Increased Mouse Survival, Tumor Growth Inhibition and Decreased Immunoreactive p53 After Exposure to Electromagnetic Fields
The possibility that magnetic fields (MF) cause antitumor activity in vivo has been investiated. Two different experiments have been carried out on nude mice bearing a subcutaneous human colon adenocarcinoma (WiDR). In the first experiment, significant increase in survival time (31%) was obtained in mice exposed daily to 70 min modulated MF (static with a superimposition of 50 Hz) having a time average total intensity of 5.5 mT. In the second independent experiment, when mice bearing tumors were exposed to the same treatment for four consecutive weeks, significant inhibition of tumor growth (40%) was reported, together with a decrement in tumor cell mitotic index and proliferative activity. A significant increase in apoptosis was found in tumors of treated animals, together with a reduction in immunoreactive p53 expression. Gross pathology at necroscopy, hematoclinical/hematological and histological examination did not show any adverse or abnormal effects. Since pharmacological rescue of mutant p53 conformation has been recently demonstrated, the authors suggest that MF exposure may obtain a similar effect by acting on redox chemistry connected to metal ions which control p53 folding and its DNA-binding activity. These findings support further investigation aimed at the potential use of magnetic fields as anti-cancer agents.
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Extremely Low Frequency (ELF) Pulsed-gradient Magnetic Fields Inhibit Malignant Tumour Growth at Different Biological Levels
Extremely low frequency (ELF) pulsed-gradient magnetic field (with the maximum intensity of
0.6–2.0 T, gradient of 10–100 T · M_1, pulse width of 20–200 ms and frequency of 0.16–1.34 Hz treatment of mice can inhibit murine malignant tumour growth, as seen from analyses at
different hierarchical levels, from organism, organ, to tissue, and down to cell and macromolecules.
Such magnetic fields induce apoptosis of cancer cells, and arrest neoangiogenesis,
preventing a supply developing to the tumour. The growth of sarcomas might be amenable to such new method of treatment.
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