Inhibition of Cancer Cell Growth by Exposure to a Specific Time-Varying Electromagnetic Field Involves T-Type Calcium Channels
Buckner CA, Buckner AL, Koren SA, Persinger MA, Lafrenie RM. Inhibition of Cancer Cell Growth by Exposure to a Specific Time-Varying Electromagnetic Field Involves T-Type Calcium Channels.PLoS One. 2015 Apr 14;10(4):e0124136. doi: 10.1371/journal.pone.0124136.
Abstract
Electromagnetic field (EMF) exposures affect many biological systems. The reproducibility of these effects is related to the intensity, duration, frequency, and pattern of the EMF. We have shown that exposure to a specific time-varying EMF can inhibit the growth of malignant cells. Thomas-EMF is a low-intensity, frequency-modulated (25-6 Hz) EMF pattern.
Daily, 1 h, exposures to Thomas-EMF inhibited the growth of malignant cell lines including B16-BL6, MDA-MB-231, MCF-7, and HeLa cells but did not affect the growth of non-malignant cells. Thomas-EMF also inhibited B16-BL6 cell proliferation in vivo. B16-BL6 cells implanted in syngeneic C57b mice and exposed daily to Thomas-EMF produced smaller tumours than in sham-treated controls. In vitro studies showed that exposure of malignant cells to Thomas-EMF for > 15 min promoted Ca2+ influx which could be blocked by inhibitors of voltage-gated T-type Ca2+ channels. Blocking Ca2+ uptake also blocked Thomas-EMF-dependent inhibition of cell proliferation. Exposure to Thomas-EMF delayed cell cycle progression and altered cyclin expression consistent with the decrease in cell proliferation. Non-malignant cells did not show any EMF-dependent changes in Ca2+ influx or cell growth.
These data confirm that exposure to a specific EMF pattern can affect cellular processes and that exposure to Thomas-EMF may provide a potential anti-cancer therapy.
Daily, 1 h, exposures to Thomas-EMF inhibited the growth of malignant cell lines including B16-BL6, MDA-MB-231, MCF-7, and HeLa cells but did not affect the growth of non-malignant cells. Thomas-EMF also inhibited B16-BL6 cell proliferation in vivo. B16-BL6 cells implanted in syngeneic C57b mice and exposed daily to Thomas-EMF produced smaller tumours than in sham-treated controls. In vitro studies showed that exposure of malignant cells to Thomas-EMF for > 15 min promoted Ca2+ influx which could be blocked by inhibitors of voltage-gated T-type Ca2+ channels. Blocking Ca2+ uptake also blocked Thomas-EMF-dependent inhibition of cell proliferation. Exposure to Thomas-EMF delayed cell cycle progression and altered cyclin expression consistent with the decrease in cell proliferation. Non-malignant cells did not show any EMF-dependent changes in Ca2+ influx or cell growth.
These data confirm that exposure to a specific EMF pattern can affect cellular processes and that exposure to Thomas-EMF may provide a potential anti-cancer therapy.
Several studies have shown associations between electromagnetic field (EMF) exposure and health effects, such as cancer incidence; however, the conclusions of these studies are sometimes difficult to reproduce and are therefore controversial. It is difficult to make direct associations between EMF exposure and health effects, since not all EMFs are equivalent [1]. For example, the biological effects of exposure to the 50–60 Hz EMF pattern from electrical power lines cannot simply be compared to the effects of exposure to the megaHz patterns generated by cell phones.
While most studies have focused on the negative effects of EMF, specific EMFs have been shown to accelerate wound healing, enhance musculoskeletal recovery, and disrupt tumor growth [2–4]. The mechanisms by which EMF affects biological processes are not well established. Some investigators have proposed that non-specific processes such as the generation of heat, formation of free-radicals, and promotion of DNA damage are involved [5–7]. However, the energies typically associated with low frequency EMF are not sufficient to cause changes in chemical bonds and other models including ion resonance have been proposed [8,9].
We hypothesize that the ability of EMFs to interact with biological processes is dependent on the temporal patterns of the fields, similar to the way pharmaceuticals are dependent on their structures [10]. Therefore, the information contained in a specific time-varying pattern, conveyed at low intensities (5–10 μT), could influence biological processes. The characteristics of an EMF that elicit biological responses should be specific for wave pattern, field strength, and exposure configuration ....
The cultured cells or mice were exposed to Thomas-EMF, a weak 2–10 μT, frequency-modulated pattern ... Thomas-EMF is a digital file composed of 849 points each programmed for 3 msec (each cycle lasts 2.55 s) (Fig 2). It is composed of 18 doublet peaks (each singlet is 6 ms) with gradually increasing intervals; a 3 ms interval for the first 5 repeats (25Hz) to a 120 ms interval (6 Hz) for the last 5 repeats. The reverse Thomas-EMF shows the same pattern except that it proceeds from 6 Hz to 25 Hz ...
Much attention has focused on the ability of low-frequency (<300 18="" 20="" a="" activation="" affect="" been="" being="" br="" ca2="" calmodulin="" camp="" can="" cell="" cells="" cellular="" channels="" commonly="" effects="" emf="" exposure="" fields="" frequency="" has="" have="" hz="" inhibits="" kinase="" levels="" low="" magnetic="" map="" most="" of="" on="" or="" others="" pathways="" pattern="" patterns="" processes="" proliferation="" promote="" reported="" shown="" signal="" simple="" sine-="" some="" square-wave="" studies="" symmetrical="" that="" the="" to="" transduction="" while="" with="">
Studies using asymmetrical EMF patterns, designed to mimic biologically-relevant processes, have shown that these complex EMF can influence specific biological processes [4, 21–23]. For example, the “Thomas” EMF pattern, a frequency modulated pattern designed to affect membrane activity associated with epileptic seizures, has been shown to have several biological effects. In particular, exposure of rodents to the Thomas-EMF pattern for 3 h/day has been associated with an increased analgesic response and to impaired memory performance on simple behavioral tasks [21, 24]. In these studies we showed that exposure to Thomas-EMF can also inhibit the growth of malignant cells by promoting Ca2+ uptake through T—type Ca2+ channels.
The results of these studies showed that exposure to a low intensity, time varying EMF, Thomas-EMF, for 1 h/day inhibited the proliferation of malignant cells by 30–50% over 5 days. Several studies have shown that exposure of cells to symmetrical (sine-wave), low intensity EMF can inhibit cell proliferation [14–17]. These studies have usually involved exposure to a specific frequency of EMF between 20 and 100Hz [17, 34]; studies using 50 and 60 Hz EMF are most common because they correlate to environmental exposures [35]. It has been proposed that these exposures decrease the growth of cell cultures by enhancing cellular apoptosis as a result of EMF-dependent increases in reactive oxygen species, rapid influx of Ca2+, or activation of specific signaling pathways [5–7, 36]. A variety of models to explain these changes in cellular responses have been proposed involving changes in temperature, flux density, or energy input [37–40]. Some studies have shown increased expression of HSP70, a marker of cellular stress responses, in response to EMF exposures [12, 41]. Exposure to EMF (or electrical fields) has been shown to compromise plasma membrane integrity to allow influx of Ca2+ or chemotherapeutics to enhance cell death [42, 43]. The Thomas-EMF pattern is quite different from a symmetrical EMF and the mechanism by which it affects cell proliferation also appears to be quite different from some of those proposed ...
The observation that Thomas-EMF can only impact proliferation of malignant cells may be related to the observation that many malignant cell lines and tumours aberrantly express T-type Ca2+ channels while non-malignant cells and HEK293 cells do not [53, 54]. For example, MCF-7 and MDA-MB-231 breast cancer cells have been shown to express T-type Ca2+ channel subunits while non-malignant breast cells do not [55, 56]. It is not clear why cancer cells express T-type Ca2+ channels although it has been correlated with increased malignant behaviour [56, 57]. Thus, exposure to Thomas-EMF might affect any cell that expresses the T type Ca2+ channel, such as sensory neurons, and may explain why Thomas-EMF inhibits pain responses in animal experiments [21, 24, 58].
The idea that Thomas-EMF can slow cell proliferation via changes in cytoplasmic Ca2+ is supported by studies that show Ca2+ is linked to changes in cell cycle progression and cyclin expression [59, 60]. Thomas-EMF delayed S phase entry for up to 8 h after the B16-BL6 cells were exposed as shown by a decrease in BrdU incorporation and consistent with the 12 h delay in cyclin E expression [61] compared to sham controls. Further, exposure to Thomas-EMF also altered cyclins A, B, and D, expression suggesting a delay at the G2/M cell cycle transition. An elevation in cyclin D levels 8 h after exposure and in cyclin B levels [62] 8–12 h after exposure are consistent with a delay in cell cycle progression through G2. Thus, the changes in cyclin expression indicate that the Thomas-EMF treated cells are delayed by 4–8 h in passing through G1/S and M phases which could account for the decreased levels of cell proliferation seen in the treated cultures.
These observations are consistent with the idea that exposure to specific EMF patterns can affect biological systems by a mechanism consistent with molecular resonance. In this case, exposure to Thomas-EMF was able to alter T-type Ca2+ channel permeability to allow an inappropriate influx of Ca2+ which was able to disrupt proliferation of malignant cells. These observations suggest that the Thomas-EMF could provide a potential anti-cancer therapy.
--
Joel M. Moskowitz, Ph.D., Director
Center for Family and Community Health
School of Public Health
University of California, Berkeley
Electromagnetic Radiation Safety
Website: http://www.saferemr.com
Facebook: http://www.facebook.com/SaferE
News Releases: http://pressroom.prlog.org/
Twitter: @berkeleyprc
While most studies have focused on the negative effects of EMF, specific EMFs have been shown to accelerate wound healing, enhance musculoskeletal recovery, and disrupt tumor growth [2–4]. The mechanisms by which EMF affects biological processes are not well established. Some investigators have proposed that non-specific processes such as the generation of heat, formation of free-radicals, and promotion of DNA damage are involved [5–7]. However, the energies typically associated with low frequency EMF are not sufficient to cause changes in chemical bonds and other models including ion resonance have been proposed [8,9].
We hypothesize that the ability of EMFs to interact with biological processes is dependent on the temporal patterns of the fields, similar to the way pharmaceuticals are dependent on their structures [10]. Therefore, the information contained in a specific time-varying pattern, conveyed at low intensities (5–10 μT), could influence biological processes. The characteristics of an EMF that elicit biological responses should be specific for wave pattern, field strength, and exposure configuration ....
The cultured cells or mice were exposed to Thomas-EMF, a weak 2–10 μT, frequency-modulated pattern ... Thomas-EMF is a digital file composed of 849 points each programmed for 3 msec (each cycle lasts 2.55 s) (Fig 2). It is composed of 18 doublet peaks (each singlet is 6 ms) with gradually increasing intervals; a 3 ms interval for the first 5 repeats (25Hz) to a 120 ms interval (6 Hz) for the last 5 repeats. The reverse Thomas-EMF shows the same pattern except that it proceeds from 6 Hz to 25 Hz ...
Much attention has focused on the ability of low-frequency (<300 18="" 20="" a="" activation="" affect="" been="" being="" br="" ca2="" calmodulin="" camp="" can="" cell="" cells="" cellular="" channels="" commonly="" effects="" emf="" exposure="" fields="" frequency="" has="" have="" hz="" inhibits="" kinase="" levels="" low="" magnetic="" map="" most="" of="" on="" or="" others="" pathways="" pattern="" patterns="" processes="" proliferation="" promote="" reported="" shown="" signal="" simple="" sine-="" some="" square-wave="" studies="" symmetrical="" that="" the="" to="" transduction="" while="" with="">
Studies using asymmetrical EMF patterns, designed to mimic biologically-relevant processes, have shown that these complex EMF can influence specific biological processes [4, 21–23]. For example, the “Thomas” EMF pattern, a frequency modulated pattern designed to affect membrane activity associated with epileptic seizures, has been shown to have several biological effects. In particular, exposure of rodents to the Thomas-EMF pattern for 3 h/day has been associated with an increased analgesic response and to impaired memory performance on simple behavioral tasks [21, 24]. In these studies we showed that exposure to Thomas-EMF can also inhibit the growth of malignant cells by promoting Ca2+ uptake through T—type Ca2+ channels.
The results of these studies showed that exposure to a low intensity, time varying EMF, Thomas-EMF, for 1 h/day inhibited the proliferation of malignant cells by 30–50% over 5 days. Several studies have shown that exposure of cells to symmetrical (sine-wave), low intensity EMF can inhibit cell proliferation [14–17]. These studies have usually involved exposure to a specific frequency of EMF between 20 and 100Hz [17, 34]; studies using 50 and 60 Hz EMF are most common because they correlate to environmental exposures [35]. It has been proposed that these exposures decrease the growth of cell cultures by enhancing cellular apoptosis as a result of EMF-dependent increases in reactive oxygen species, rapid influx of Ca2+, or activation of specific signaling pathways [5–7, 36]. A variety of models to explain these changes in cellular responses have been proposed involving changes in temperature, flux density, or energy input [37–40]. Some studies have shown increased expression of HSP70, a marker of cellular stress responses, in response to EMF exposures [12, 41]. Exposure to EMF (or electrical fields) has been shown to compromise plasma membrane integrity to allow influx of Ca2+ or chemotherapeutics to enhance cell death [42, 43]. The Thomas-EMF pattern is quite different from a symmetrical EMF and the mechanism by which it affects cell proliferation also appears to be quite different from some of those proposed ...
The observation that Thomas-EMF can only impact proliferation of malignant cells may be related to the observation that many malignant cell lines and tumours aberrantly express T-type Ca2+ channels while non-malignant cells and HEK293 cells do not [53, 54]. For example, MCF-7 and MDA-MB-231 breast cancer cells have been shown to express T-type Ca2+ channel subunits while non-malignant breast cells do not [55, 56]. It is not clear why cancer cells express T-type Ca2+ channels although it has been correlated with increased malignant behaviour [56, 57]. Thus, exposure to Thomas-EMF might affect any cell that expresses the T type Ca2+ channel, such as sensory neurons, and may explain why Thomas-EMF inhibits pain responses in animal experiments [21, 24, 58].
The idea that Thomas-EMF can slow cell proliferation via changes in cytoplasmic Ca2+ is supported by studies that show Ca2+ is linked to changes in cell cycle progression and cyclin expression [59, 60]. Thomas-EMF delayed S phase entry for up to 8 h after the B16-BL6 cells were exposed as shown by a decrease in BrdU incorporation and consistent with the 12 h delay in cyclin E expression [61] compared to sham controls. Further, exposure to Thomas-EMF also altered cyclins A, B, and D, expression suggesting a delay at the G2/M cell cycle transition. An elevation in cyclin D levels 8 h after exposure and in cyclin B levels [62] 8–12 h after exposure are consistent with a delay in cell cycle progression through G2. Thus, the changes in cyclin expression indicate that the Thomas-EMF treated cells are delayed by 4–8 h in passing through G1/S and M phases which could account for the decreased levels of cell proliferation seen in the treated cultures.
These observations are consistent with the idea that exposure to specific EMF patterns can affect biological systems by a mechanism consistent with molecular resonance. In this case, exposure to Thomas-EMF was able to alter T-type Ca2+ channel permeability to allow an inappropriate influx of Ca2+ which was able to disrupt proliferation of malignant cells. These observations suggest that the Thomas-EMF could provide a potential anti-cancer therapy.
--
Joel M. Moskowitz, Ph.D., Director
Center for Family and Community Health
School of Public Health
University of California, Berkeley
Electromagnetic Radiation Safety
Website: http://www.saferemr.com
Facebook: http://www.facebook.com/SaferE
News Releases: http://pressroom.prlog.org/
Twitter: @berkeleyprc
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