DC electrical field-induced c-fos expression and growth stimulation in multicellular prostate cancer spheroids.
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.
Sauer
H
H
Department of Neurophysiology, University of Cologne, Germany.
Hescheler
J
J
Reis
D
D
Diedershagen
H
H
Niedermeier
W
W
Wartenberg
M
M
D002021:Buffers; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D004553:Electric Conductivity; D004574:Electromagnetic Fields; D015870:Gene Expression; D016762:Genes, fos; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009336:Necrosis; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D018874:Spheroids, Cellular; D014407:Tumor Cells, Cultured
D002021:Buffers; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos