8-Methoxybutin inhibits α-MSH induced melanogenesis and proliferation of skin melanoma by suppression of the transactivation activity of microphthalmia-associated transcription factor - 18/06/22
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Abstract |
Microphthalmia-associated transcription factor (MITF) is highly expressed in melanocytes and is the main regulator of melanogenesis and melanocyte cell fate. Although MITF is important for the differentiation and development of melanocytes, it is also considered an oncogene of skin melanoma. Based on these findings, MITF could be an attractive therapeutic target for skin cancer intervention. This study identified 8-methoxybutin as an inhibitor of MITF and investigated the underlying mechanism. 8-Methoxybutin inhibited α-MSH-induced melanogenesis in murine melanoma cells (B16F10) and skin melanoma proliferation by reducing melanogenic gene expression via blockade of the transactivation activity of MITF. In silico docking analysis and pull-down analysis suggested that 8-methoxybutin binds to the DNA-binding domain of MITF and further inhibits its binding to the E-box in the promoter of target genes, including tyrosinase. In addition, 8-methoxybutin suppressed growth of skin melanoma in a xenograft mouse model. These results indicate that 8-methoxybutin has potential as a therapeutic agent for hyperpigmentation disorder and skin cancer.
Significance statement |
8-Methoxybutin inhibits MITF transactivation activity resulting suppression of melanogenesis and skin melanoma growth.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
● | 8-Methoxybutin inhibited α-MSH-induced melanogenesis in murine melanoma cells by reducing the target gene expression of MITF. |
● | DNA-binding domain of MITF is blocked by directly binding of 8-methoxybutin and transactivation activity is decreased. |
● | 8-methoxybutin suppressed proliferation of murine melanoma cell line and growth of skin melanoma in a xenograft mouse model. |
Keywords : 8-methoxybutin, Anti-melanogenic effect, Flavonoid, MITF, Skin melanoma
Plan
Vol 152
Article 113272- août 2022 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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