title: Stimulation of tyrosinase activity and melanin formation of cultured melanoma cells by serum deprivation alone or in combination with dibutyryl cyclic AMP and theophylline.
abstract: Serum removal from the media of serial monolayer cultures of the Harding-Passey melanoma during an incubation period of 3 days resulted in an exponentially declining DNA synthesis rate (measured by the incorporation of [14C]thymidine) and in an inhibition of cell proliferation. Protein synthesis, as measured by the incorporation of radioactive leucine, was less affected than DNA synthesis. Incubation in serum-free culture medium resulted in significant rises of tyrosinase activity and cellular melanin content. Addition of dibutyryl adenosine 3':5' monophosphate (Bu2cAMP, 5X10(-4) M) and theophylline (5X10(-4) M) to serum-free cultures caused a further striking increase of tyrosinase activity and melanin formation, while treatment of serum containing cultures with Bu2cAMP and theophylline showed only a slight rise in melanogenesis. It is suggested that these stimulatory effects are mediated by an increased intracellular cAMP level, since a correlation between the degree of melanogenesis and cellular cAMP content was indicated. Treatment of serum-free or serum-containing cultures with the phosphodiesterase inhibitor theophylline (5X10(-4)--10(-3)M) alone revealed only a slight enhancement (about 20%) of melanogenesis. Because augmentation of melanogenesis by serum-free medium alone or together with Bu2cAMP and theophylline was prevented by cycloheximide (or actinomycin D), de novo protein synthesis seems to be required for these stimulatory effects.
mesh_terms: D001769:Blood; D003994:Bucladesine / Q000494:pharmacology*; D004156:Catechol Oxidase / Q000378:metabolism*; D002460:Cell Line; D003470:Culture Media; D004273:DNA, Neoplasm / Q000096:biosynthesis; D007930:Leucine / Q000378:metabolism; D008543:Melanins / Q000096:biosynthesis*; D008545:Melanoma / Q000378:metabolism*; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000096:biosynthesis; D013806:Theophylline / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
chemical_list: D003470:Culture Media; D004273:DNA, Neoplasm; D008543:Melanins; D009363:Neoplasm Proteins; D014443:Tyrosine; D003994:Bucladesine; D013806:Theophylline; D004156:Catechol Oxidase; D014442:Monophenol Monooxygenase; D007930:Leucine; D013936:Thymidine