[NLE4, D-PHE7]-$aL-MSH: A Superpotent Melanotropin That “Irreversibly” Activates Melanoma Tyrosinase

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Abstract
The superpotent and ultraprolonged melanotropic properties of an α-melanotropin analog, [Nle4, D-Phe]-α-MSH, were investigated in a Cloudman S91 (CCL 53.1) melanoma cell line. [Nle4, D-Phe7]-α-MSH is 100-fold more effective than the native hormone, α-MSH), in stimulating hormone (α-MSH), in stimulating melanoma cell tyrosinase activity, as determined from their minimum effective doses (10−11M and 10−9M, respectively). [Nle4, D-Phe7]-α-MSH also exhibits a more sustained effect than α-MSH on tyrosinase after removal of the melanotropins from the incubation medium. When cells were exposed to α-MSH (10−7M) for 24 h, residual activity after removal of the hormone was minimally significant. In contrast, under the same experimental conditions [Nle4, D-Phe]-α-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, α-MSH failed to elicit significant tyrosinase activity, whereas [Nle4, D-Phe]-α-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.