[Nle4, D-Phe7]-alpha-MSH: a superpotent melanotropin that "irreversibly" activates melanoma tyrosinase.
The superpotent and ultraprolonged melanotropic properties of an alpha-melanotropin analog, [Nle4, D-Phe7]-alpha-MSH, were investigated in a Cloudman S91 (CCL 53.1) melanoma cell line. [Nle4, D-Phe7]-alpha-MSH is 100-fold more effective than the native hormone, alpha-melanocyte stimulating hormone (alpha-MSH), in stimulating melanoma cell tyrosinase activity, as determined from their minimum effective doses (10(-11)M and 10(-9)M, respectively). [Nle4, D-Phe7]-alpha-MSH also exhibits a more sustained effect than alpha-MSH on tyrosinase after removal of the melanotropins from the incubation medium. When cells were exposed to alpha-MSH (10(-7)M) for 24 h, residual activity after removal of the hormone was minimally significant. In contrast, under the same experimental conditions [Nle4, D-Phe7]-alpha-MSH treatment induced tyrosinase activity 2-3 fold above basal level, and maintained remarkable stimulatory effects up to 72 h following melanotropin removal. When the exposure time to melanotropins was reduced to 4 h, alpha-MSH failed to elicit significant tyrosinase activity, whereas [Nle4, D-Phe7]-alpha-MSH stimulated significant tyrosinase activity during the first 24 h subsequent to melanotropin removal. Interestingly, this stimulation by the analog increased at 48 h, reached a maximum at 72 h following removal of the melanotropin analog, and remained significantly stimulated for 6 consecutive days in the absence of the analog.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D004156:Catechol Oxidase / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D009074:Melanocyte-Stimulating Hormones / Q000031:analogs & derivatives* / Q000494:pharmacology; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism*; D051379:Mice; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D011979:Receptors, Pituitary Hormone; D013997:Time Factors; D000521:alpha-MSH / Q000031:analogs & derivatives*
D011956:Receptors, Cell Surface; D011979:Receptors, Pituitary Hormone; D000521:alpha-MSH; C027756:MSH, 4-Nle-7-Phe-alpha-; C029446:MSH receptor; D009074:Melanocyte-Stimulating Hormones; D004156:Catechol Oxidase; D014442:Monophenol Monooxygenase; D000262:Adenylyl Cyclases