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Inhibition of cancer cell growth by exposure to a specific time-varying electromagnetic field involves T-type calcium channels.

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 Ca(2+) influx which could be blocked by inhibitors of voltage-gated T-type Ca(2+) channels. Blocking Ca(2+) 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 Ca(2+) 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.

SUBMITTER: Buckner CA

PROVIDER: S-EPMC4397079 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Inhibition of cancer cell growth by exposure to a specific time-varying electromagnetic field involves T-type calcium channels.

Buckner Carly A CA Buckner Alison L AL Koren Stan A SA Persinger Michael A MA Lafrenie Robert M RM

PloS one 20150414 4

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 n ...[more]

PMID: 25875081

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Project description:PurposeIn studies of effects of time-varying drug exposures, adequate adjustment for time-varying covariates is often necessary to properly control for confounding. However, the granularity of the available covariate data may not be sufficiently fine, for example when covariates are measured for participants only when their exposure levels change.MethodsTo illustrate the impact of choices regarding the frequency of measuring time-varying covariates, we simulated data for a large target trial and for large observational studies, varying in covariate measurement design. Covariates were measured never, on a fixed-interval basis, or each time the exposure level switched. For the analysis, it was assumed that covariates remain constant in periods of no measurement. Cumulative survival probabilities for continuous exposure and non-exposure were estimated using inverse probability weighting to adjust for time-varying confounding, with special emphasis on the difference between 5-year event risks.ResultsWith monthly covariate measurements, estimates based on observational data coincided with trial-based estimates, with 5-year risk differences being zero. Without measurement of baseline or post-baseline covariates, this risk difference was estimated to be 49% based on the available observational data. With measurements on a fixed-interval basis only, 5-year risk differences deviated from the null, to 29% for 6-monthly measurements, and with magnitude increasing up to 35% as the interval length increased. Risk difference estimates diverged from the null to as low as -18% when covariates were measured depending on exposure level switching.ConclusionOur simulations highlight the need for careful consideration of time-varying covariates in designing studies on time-varying exposures. We caution against implementing designs with long intervals between measurements. The maximum length required will depend on the rates at which treatments and covariates change, with higher rates requiring shorter measurement intervals.

Project description:Background and purposePre-synaptic neurotransmitter release is largely dependent on Ca(2+) entry through P/Q-type (Ca(V)2.1) voltage-gated Ca(2+) channels (PQCCs) at most mammalian, central, fast synapses. Barbiturates are clinical depressants and inhibit pre-synaptic Ca(2+) entry. PQCC barbiturate pharmacology is generally unclear, specifically in man. The pharmacology of the barbiturate pentobarbital (PB) in human recombinant alpha(1A) PQCCs has been characterized.Experimental approachPB effects on macroscopic Ca(2+)(I(Ca)) and Ba(2+)(I(Ba)) currents were studied using whole-cell patch clamp recording in HEK-293 cells heterologously expressing (alpha(1A))(human)(beta(2a)alpha(2)delta-1)(rabbit) PQCCs.Key resultsPB reversibly depressed peak current (I(peak)) and enhanced apparent inactivation (fractional current at 800 ms, r(800)) in a concentration-dependent fashion irrespective of charge carrier (50% inhibitory concentration: I(peak), 656 microM; r(800), 104 microM). Rate of mono-exponential I(Ba) decay was linearly dependent on PB concentration. PB reduced channel availability by deepening non-steady-state inactivation curves without altering voltage dependence, slowed recovery from activity-induced unavailable states and produced use-dependent block. PB (100 microM) induced use-dependent block during physiological, high frequency pulse trains and overall depressed PQCC activity by two-fold.Conclusion and implicationsThe results support a PB pharmacological mechanism involving a modulated receptor with preferential slow, bimolecular, open channel block (K(d)= 15 microM). Clinical PB concentrations (<200 microM) inhibit PQCC during high frequency activation that reduces computed neurotransmitter release by 16-fold and is comparable to the magnitude of Ca(2+)-dependent facilitation, G-protein modulation and intrinsic inactivation that play critical roles in PQCC modulation underlying synaptic plasticity. The results are consistent with the hypothesis that PB inhibition of PQCCs contributes to central nervous system depression underlying anticonvulsant therapy and general anaesthesia.

Project description:Some studies have shown that people living near a mobile phone base station may report sleep disturbances and discomfort. Using a rat model, we have previously shown that chronic exposure to a low-intensity radiofrequency electromagnetic field (RF-EMF) was associated with paradoxical sleep (PS) fragmentation and greater vasomotor tone in the tail. Here, we sought to establish whether sleep disturbances might result from the disturbance of thermoregulatory processes by a RF-EMF. We recorded thermal preference and sleep stage distribution in 18 young male Wistar rats. Nine animals were exposed to a low-intensity RF-EMF (900 MHz, 1 V x m(-1)) for five weeks and nine served as non-exposed controls. Thermal preference was assessed in an experimental chamber comprising three interconnected compartments, in which the air temperatures (Ta) were set to 24°C, 28°C and 31°C. Sleep and tail skin temperature were also recorded. Our results indicated that relative to control group, exposure to RF-EMF at 31°C was associated with a significantly lower tail skin temperature (-1.6°C) which confirmed previous data. During the light period, the exposed group preferred to sleep at Ta?=?31°C and the controls preferred Ta?=?28°C. The mean sleep duration in exposed group was significantly greater (by 15.5%) than in control group (due in turn to a significantly greater amount of slow wave sleep (SWS, +14.6%). Similarly, frequency of SWS was greater in exposed group (by 4.9 episodes.h-1). The PS did not differ significantly between the two groups. During the dark period, there were no significant intergroup differences. We conclude that RF-EMF exposure induced a shift in thermal preference towards higher temperatures. The shift in preferred temperature might result from a cold thermal sensation. The change in sleep stage distribution may involve signals from thermoreceptors in the skin. Modulation of SWS may be a protective adaptation in response to RF-EMF exposure.

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Inhibition of cancer cell growth by exposure to a specific time-varying electromagnetic field involves T-type calcium channels.

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Inhibition of cancer cell growth by exposure to a specific time-varying electromagnetic field involves T-type calcium channels.

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