Isolation and characterization of high molecular weight melanogenic inhibitors naturally occurring in melanoma cells.
Intrinsic melanogenic inhibitors with high molecular weights have been isolated from Greene's amelanotic hamster melanoma by DEAE ion-exchange and gel filtration chromatographies. The native molecular weights of two partially purified inhibitors have been determined to be 15 kDa (beta-type) and 67 kDa (gamma-type), respectively, using HPLC gel filtration. Both types of inhibitors, despite their inability to directly inhibit isolated tyrosinase, have been shown to markedly inhibit melanin formation in cultured B16 cells. In contrast to the beta-type inhibitor, the gamma-type inhibitor can induce depigmentation in B16 cells without abolishing their internal tyrosinase activity. Further, it has been determined that both inhibitors contain various amounts of unsaturated fatty acids, C15:1, C18:1, C18:2, C18:3, C20:3, and C20:4, which exhibit depigmentary activities on cultured B16 cells. C15:1 is low in the beta-type, but high in the gamma-type whereas C18:3 is high in the beta-type but low in the gamma-type. These results suggest that the differential action of these inhibitors is most likely due to the composition of the unsaturated fatty acids.
Mishima Institute for Dermatological Research, Kobe, Japan.
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Ohyama
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Mishima
D000818:Animals; D002460:Cell Line / Q000187:drug effects; D006224:Cricetinae; D005227:Fatty Acids / Q000032:analysis / Q000494:pharmacology; D008074:Lipoproteins / Q000302:isolation & purification / Q000494:pharmacology*; D008543:Melanins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008546:Melanoma, Experimental / Q000737:chemistry*; D008647:Mesocricetus; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000302:isolation & purification*; D010858:Pigmentation / Q000187:drug effects
D005227:Fatty Acids; D008074:Lipoproteins; D008543:Melanins; D009363:Neoplasm Proteins