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DC electrical field-induced c-fos expression and growth stimulation in multicellular prostate cancer spheroids
1Department of Neurophysiology, University of Cologne, Germany.
Abstract:
The effects of electrical direct current (DC) field pulses on c-fos expression, growth kinetics and vitality patterns of multicellular tumour spheroids (MCSs) were studied. Monitoring the membrane potential of MCSs by di-8-ANNEPS staining and confocal microscopy during DC electrical field treatment revealed a hyperpolarization at the anode-facing side and a depolarization at the cathode-facing side. When a single 500 V m(-1) electrical field pulse with a duration of 60 s was applied to MCSs (150-350 microm in diameter) an enhancement of the growth kinetics within a period of 6 days post pulse was observed. Whereas the volume doubling time amounted to 4-5 days in control samples, it was reduced to 1-2 days in electropulsed MCSs. At day 6 post pulse the diameter of the necrotic core was significantly smaller than the control. The critical diameter for the first appearance of central necrosis amounted to 350 +/- 50 microm in the control and 450 +/- 50 microm in the electropulsed MCSs. Coincidentally, the proliferating rim was increased to 107 +/- 11 microm in electropulsed MCSs as compared with 60 +/- 6 microm in the control. The growth stimulation may be mediated by the proto-oncogene c-fos as its expression increased by a factor of 2.5 within 2 h post pulse. c-fos expression declined towards control values within 8 h post pulse.
Insights
Electrical direct current (DC) field pulses enhance multicellular tumor spheroid (MCS) growth kinetics and reduce necrosis. This growth stimulation is linked to increased c-fos expression following electropulsation.
Area of Science:
- Biophysics
- Cell Biology
- Oncology
Background:
- Multicellular tumor spheroids (MCSs) are used to model tumor microenvironments.
- Understanding cellular responses to electrical fields is crucial for developing novel cancer therapies.
Purpose of the Study:
- To investigate the effects of direct current (DC) electrical field pulses on MCS growth, vitality, and gene expression.
- To determine the impact of electropulsation on c-fos expression and its relation to growth kinetics.
Main Methods:
- MCSs were treated with single DC electrical field pulses (500 V m(-1), 60 s).
- Membrane potential was monitored using di-8-ANNEPS staining and confocal microscopy.
- Growth kinetics, necrotic core size, and proliferating rim were assessed post-treatment.
- c-fos gene expression was quantified at various time points.
Main Results:
- Electropulsation induced membrane potential changes (hyperpolarization/depolarization).
- A significant enhancement in MCS growth kinetics was observed, with reduced volume doubling time (1-2 days vs. 4-5 days).
- Electropulsed MCSs showed a smaller necrotic core and an increased proliferating rim.
- c-fos expression increased 2.5-fold within 2 hours post-pulse, returning to baseline by 8 hours.
Conclusions:
- DC electrical field pulses can stimulate MCS growth and alter tumor spheroid architecture.
- The proto-oncogene c-fos may mediate the observed growth stimulation following electropulsation.
- These findings suggest potential applications of electrical stimulation in cancer research and therapy.