Effect of hyperthermia in combination with vitamin E and cyclic AMP on neuroblastoma cells in culture

The effect of heat in combination with DL-alpha-tocopheryl (vitamin E) succinate and adenosine 3', 5'-cyclic monophosphate (cAMP) stimulating agents on mouse neuroblastoma cells ( NBP2 ) in culture on the criterion of growth inhibition (due to cell death and inhibition of cell division) was studied. Heat (41 degrees-40 degrees) alone inhibited growth; however, the extent of growth inhibition was dependent upon the temperature and the time of heat treatment. Heat (41 degrees-40 degrees) in combination with vitamin E succinate (5 micrograms/ml) produced an additive effect on the criterion of growth inhibition. Vitamin C (100 micrograms/ml) failed to modify the effect of heat. Prostaglandin A2, a stimulator of adenylate cyclase, and 4 - (3-butoxy-4-methoxybenzyl)-2-imidazolidinone ( R020 -1724), an inhibitor of cyclic nucleotide phosphodiesterase, are known to induce irreversible differentiation in mouse neuroblastoma cells in culture. These agents, in combination with heat (40 degrees) produced a synergistic effect on the criterion of growth inhibition. These data suggest that the addition of vitamin E and cAMP stimulating agents may increase the effectiveness of hyperthermia protocol.