Combined effect of adenosine 3′, 5′-cyclic monophosphate stimulating agents, vitamin e succinate, and heat on the survival of murine b-16 melanoma cells in culture

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Abstract
An elevation of the intracellular level of cAMP by 4‐(3‐butoxy‐4‐methoxybenzyl)‐2‐imidazolidinone (R020–1724) during heat treatment (41°C for 10 hours) markedly reduced the survival of murine B‐16 melanoma cells in culture; however, heat alone or R020–1724 treatment at 37°C for 10 hours was ineffective. D‐alpha‐tocopheryl succinate (vitamin E succinate), which did not increase cAMP level, reduced the survival of heated cells to a greater degree than with vitamin E succinate alone. The presence of vitamin E succinate for the entire experimental period (during heat and observation period) was necessary for this effect. R020–1724 in combination with vitamin E succinate was more effective in reducing the survival of heated cells than the individual agents. Although prostaglandin (PG) A2 did not increase cAMP level in melanoma cells, it decreased the survival of heated cells when present during heat treatment. Other forms of PG such as PGE1 and PGF2α were ineffective. The combination of R020–1724 with two non‐cAMP stimulating agents, PGA2 and vitamin E succinate, decreased the survival of heated cells by about 94% of control. These results suggest that the heat sensitivity of melanoma cells can be increased by cAMP‐dependent and ‐independent mechanisms.