MSH receptor expression and the relationship to melanogenesis and metastatic activity in B16 melanoma.
Lunec. J J; Pieron. C C; Thody. A J AJ
Key Findings
- Melanotan‑I (Nle4DPhe7‑alpha‑MSH) strongly stimulates both melanin production and metastatic activity in B16 melanoma cells.
- The order of potency for melanogenesis matches that for metastasis, except ACTH[1‑24] which boosts metastasis more than expected.
- Binding affinity to the MSH receptor does not fully predict how much the peptide will trigger pigment or metastasis.
Practical Outcomes
- For biohackers using melanotan‑I for tanning, the data suggest a potential risk of promoting cancer cell spread, especially in people with existing skin lesions or a history of melanoma. It’s wise to avoid melanotan‑I if you have any skin cancer risk factors and to monitor skin health closely if you choose to use it. This study reinforces the need for caution rather than providing a new dosing protocol.
Summary
The study looked at how different hormone-like peptides, including melanotan‑I (a synthetic version of alpha‑MSH), affect skin pigment production and the spread of melanoma cells in the lab. All the peptides boosted pigment, but they also increased the cells' ability to spread, with melanotan‑I being the most potent. The researchers found that the strength of the effect isn’t just about how tightly the peptide binds to its receptor.
Abstract
In this study we have compared the effects of different pro-opiomelanocortin (POMC) peptides on melanogenesis and metastasis and their relationship to MSH receptor expression in B16F1 melanoma cells. All peptides, apart from beta-endorphin, increased melanogenesis and the order of potency was Nle4DPhe7-alpha-MSH greater than alpha-MSH greater than ACTH[1-39] greater than des-acetyl alpha-MSH greater than ACTH[1-24]. A similar order of potency was found for metastasis, except for ACTH [1-24], which had a relatively greater effect on metastasis. These findings suggest that the effects on melanogenesis and metastasis are mediated via the same receptor. The results of ligand binding studies also indicated the presence of a single receptor with a KD value for Nle4DPhe7-alpha-MSH of 62 +/- 16pM. This was consistent with crosslinking studies using [125I] Nle4DPhe7-alpha-MSH which produced a single 50-55 kD band on analysis by SDS-PAGE. However, the relative binding affinities of the different peptides, measured by displacement of [125I]-Nle4DPhe7-alpha-MSH, did not closely correlate with the relative potencies in stimulating melanogenesis and metastasis. This suggests that receptor activation and the subsequent biological response is not determined solely by binding affinity.
Study Information
pubmed
1992
1992-05-01T00:00:00.000Z
10.1097/00008390-199205000-00002
43