Induction of differentiated phenotypes in melanoma cells by a combination of an adenosine 3',5'-cyclic monophosphate stimulating agent and D-alpha tocopheryl succinate.
The purpose of this investigation was to identify those agents and combinations of agents that help convert murine melanoma cells to cells of differentiated (normal-like) phenotype in culture. The agents used were 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (R020-1724), which is an adenosine 3',5'-cyclic monophosphate (cAMP) phosphodiesterase inhibitor that has never been tested on melanoma cells in culture, and d-alpha tocopheryl succinate (vitamin E succinate), which has previously been shown to inhibit growth and induce morphological differentiation in melanoma cells. The results indicated that R020-1724 by itself inhibited growth, reduced survival, caused morphological differentiation and increased the melanin content (one of the biochemical differentiated functions) in melanoma cells. Vitamin E succinate had a similar effect on the melanoma cells, which supports past research on this vitamin. A combination of R20-1724 and vitamin E succinate had a significantly greater effect on the melanoma cells than either of the agents by themselves. The agents identified in this study may provide useful tools for studying the mechanisms of differentiation in melanoma cells.
Prasad
K C
KC
Department of Radiology, University of Colorado Health Sciences Center, School of Medicine, Denver 80262.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D008543:Melanins / Q000032:analysis; D008546:Melanoma, Experimental / Q000032:analysis / Q000473:pathology*; D051379:Mice; D010641:Phenotype; D024505:Tocopherols; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology
D007093:Imidazoles; D008543:Melanins; C048819:4-(3,4-dibutoxybenzyl)-2-imidazolidinone; D014810:Vitamin E; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D024505:Tocopherols