Melanotropic Peptides: more than Just 'Barbie Drugs' and 'Sun-tan Jabs'?

E.A. Langan; Z. Nie; L.E. Rhodes

Disclosures

The British Journal of Dermatology. 2010;163(3):451-455. 

In This Article

Unregulated Use and Cutaneous Concerns

Langan et al.[29] first raised concerns in 2009 about the impact in the dermatological context of the use of illegally advertised and sold chemicals labelled melanotan I and II. Two women presented to the dermatology clinic after noticing changes in the appearance of their pre-existing melanocytic naevi, which markedly darkened in colour after using courses of self-injected melanotan I and/or II.[29] They both had a past history of sun-seeking behaviour and sunbed use. After removal, the histology of these naevi ranged from benign broad acral naevi to a compound dysplastic naevus with histological features of concern, including dermal expansile nests and dermal melanocytic atypia. Both patients were phototype I/II (sunburn easily, suntan with difficulty) but presented with conspicuous tans. Thus, unregulated use of chemicals labelled melanotan I and/or II may be associated with changes in the clinical appearance of naevi that distort the clinical presentation, and an unexpected tan can be a clue to their use.

Subsequently, Cardones and Grichnik[30] reported the development of new pigmented naevi, exhibiting atypical clinical and histological features, in a 40-year-old man with a past history of melanoma, who had used a product labelled melanotan II. With cessation of the agent the naevi lightened and lost their growth features. The patient's history of sun exposure and sunbed use was not reported. Cousen et al.[31] also recently reported a 19-year-old woman who developed eruptive melanocytic naevi following the use of melanotan II. Furthermore, Ellis et al.[32] reported a case of malignant melanoma in a melanotan I user. While the authors did not suggest there was a causal link between the use of melanotan and the development of melanoma, they again stressed the difficulties in assessing melanocytic lesions in users of melanotan, who typically are or have been sun seekers.

Both in vitro and in vivo studies have failed to demonstrate a carcinogenic potential of α-MSH analogues.[33] In fact, in cultured melanoma cell lines, [Nle4-D-Phe7]-α-MSH inhibited melanoma cell proliferation in vitro.[34] Normal human melanocytes, treated with [Nle4-D-Phe7]-α-MSH and injected into SCID mice, were unable to grow, suggesting no malignant transformation had taken place.[35] It has also been observed that α-MSH analogues enhance repair of DNA photoproducts in melanocytes exposed to UVR.[35,36] The parent α-MSH molecule has shown conflicting effects, on the one hand being associated with immunosuppressive properties in experimental models,[37] while on the other, recent work provides evidence that α-MSH augments antitumoral activity, through induction of cytolytic activity in human tumour-specific CD8+ cells.[14] Further studies are evaluating these properties in α-MSH analogues.

Presently, it is unknown whether regulated α-MSH analogue treatment will decrease the risk of skin cancers in people prone to these. Clinical studies in healthy humans uphold the assumption that the resultant melanization conveys protection against the sunburn and DNA damage associated with UVR exposure. These and other properties of the analogues and natural α-MSH as explored in experimental systems largely support their protective effects, although further in vitro and in vivo study is required. The analogues increase pigmentation of both healthy skin and melanocytic naevi, and reports of dysplastic changes in moles of tan-seeking individuals using unregulated melanotropic chemicals are interpreted to be a consequence of the risk profile, i.e. UVR-exposure behaviour, of these individuals. Nevertheless, the question has been posed as to whether α-MSH analogues may in some circumstances bear a negative influence on melanocytes/melanoma cells.

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