Terrein: a new melanogenesis inhibitor and its mechanism

Abstract

Terrein is a bioactive fungal metabolite whose effects are almost unknown. In this study, we found for the first time that terrein has a strong hypopigmentary effect in a spontaneously immortalized mouse melanocyte cell line, Mel-Ab. Treatment of Mel-Ab cells with terrein (10-100 microM) for 4 days significantly reduced melanin levels in a dose-dependent manner. In addition, terrein at the same concentration also reduced tyrosinase activity. We then investigated whether terrein influences the extracellular signal-regulated protein kinase (ERK) pathway and the expression of microphthalmia-associated transcription factor (MITF), which is required for tyrosinase expression. Terrein was found to induce sustained ERK activation and MITF down-regulation, and luciferase assays showed that terrein inhibits MITF promoter activity in a dose-dependent manner. To elucidate the correlation between ERK pathway activation and a decreased MITF transcriptional level, PD98059, a specific inhibitor of the ERK pathway, was applied before terrein treatment and found to abrogate the terrein-induced MITF attenuation. Terrein also reduced the tyrosinase protein level for at least 72 h. These results suggest that terrein reduces melanin synthesis by reducing tyrosinase production via ERK activation, and that this is followed by MITF down-regulation.

A New Terrein Glucoside, a Novel Inhibitor of Angiogenin Secretion in Tumor Angiogenesis

“…However, the biological effects of 2 have been almost unknown. Recently, 2 was reported to inhibit the melanogenesis [20] and the epidermal proliferation of skin equivalents [21]. Although whether 2 affects the angiogenesis-related factors has been unknown before, we have shown here that 1 and 2 inhibited angiogenin secretion from LNCaP-CR cells with IC 50 values of 13 mM, respectively (Table 3).…”

Effects of wogonin on the mechanism of melanin synthesis in A375 cells

“…Park et al (18) indicated that the activated ERK pathway may inhibit melanin synthesis through decreasing the expression of the microphthalmia-associated transcription factor gene, and an alternative study suggested the p38 MAPK pathway may promote melanin synthesis through increasing the expression of the tyrosinase gene (19). Furthermore the JNK pathway may be implicated in the inhibition of melanin synthesis (20).…”

A Novel Melanin Inhibitor: Hydroperoxy Traxastane-Type Triterpene from Flowers of Arnica montana

“…The melanin inhibition effect of compound [1] was not due to cytotoxicity, because the melanin assay was performed by adjusting the number of cells and the inhibition of cell growth was observed at the concentration of 0.25 mg/ml (0.53 mM). Several other melanin biosynthesis inhibitors that do not inhibit tyrosinase activity have been isolated from plants; these include 4,5-dihydroxy-3-propenyl-2-cyclopenten-1-one (terrein; IC 50 Լ30 mM) from Penicillium species, 21) piperlonguminine (IC 50 Լ10 mM) from Piper longum (Piperaceae), 12) and coumarin compounds such as soimperatorin and imperatorin (IC 50 Ͼ100 mM) from Angelica dahurica. 22) Thus, compound [1] is one of the most potent melanin Total RNA was extracted from cells were cultured for 1 d in medium containing 0.125 mg/ml of 3b,16b-dihydroxy-21a-hydroperoxy-20(30)-taraxastene [1].…”