Manassantin A inhibits cAMP-induced melanin production by down-regulating the gene expressions of MITF and tyrosinase in melanocytes.

College of Pharmacy, Yeungnam University, Kyungsan, Korea College of Pharmacy, Chungbuk National University, Cheongju, Korea College of Pharmacy, Chungnam National University, Daejeon, Korea.
Experimental Dermatology (Impact Factor: 4.12). 05/2011; 20(9):761-3. DOI: 10.1111/j.1600-0625.2011.01296.x
Source: PubMed

ABSTRACT Microphthalmia-associated transcription factor (MITF) is inducible in response to cAMP through the cAMP-responsive element-binding protein (CREB) and plays a pivotal role in the melanocyte-specific expression of tyrosinase or tyrosinase-related proteins (TRPs) for melanin biosynthesis. Manassantin A from Saururus chinensis inhibits cAMP-induced melanin production in B16 melanoma cells. Here, we focused on molecular basis of the antimelanogenic activity. Manassantin A consistently inhibited the cAMP elevator 3-isobutyl-1-methylxanthine (IBMX)- or dibutyryl cAMP-induced melanin production in B16 cells or in melan-a melanocytes by down-regulating the expression of tyrosinase or TRP1 gene. Moreover, manassantin A suppressed MITF induction through IBMX-activated CREB pathway, directly inhibiting the Ser-133 phosphorylation of CREB. However, manassantin A did not affect IBMX-increased cAMP levels in these cells but also other cAMP-dependent melanogenic pathways through post-translational modifications of MITF. This putative molecular mechanism of manassantin A in the inhibition of melanin production suggests its pharmacological potential in skin hyperpigmentation.

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    ABSTRACT: Objectives : The purpose of this study was to investigate the melanogenesis inhibition effect of Saururus chinensis BAILL (SC) on in B16F10 melanoma cells. Methods : SC was fractionated ethanol extract by the hexane, ethyl acetate, butanol and water. We confirmed the inhibitory effect of tyrosinase activity and melanogenesis of all fraction samples. Results : Hexane fraction of Saururus chinensis BAILL (HSC), ethyl acetate of SC (ESC), and butanol of SC (BSC) were discovered to inhibit tysoinase activity and melanogenesis in the absence or presence of -MSH. However, water fraction of SC (WSC) did not affect tyrosinase activity and melanogenesis. In addition, all fractions did not inhibit the catalytic activity of cell-free tyrosinase from B16F10 melanoma cell lines. Conclusions : These results suggest that HSC, ESC and BSC reduce pigmentation by indirectly regulating tyrosinase.
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    ABSTRACT: The dineolignan manassantin A from Saururaceae was recently identified as a hypoxia-inducible factor 1 (HIF-1) inhibitor, but its in-vivo anti-tumor effect has not been explored. We synthesized a series of manassantin A derivatives, and found that replacing the central tetrahydrofuran moiety with a cyclopentane ring yielded a compound (LXY6006) with increased HIF-1-inhibitory activity yet decreased stereochemically complexity amenable to a simplified synthesis scheme. LXY6006 inhibited HIF-1α nuclear accumulation induced by hypoxia, and inhibited cancer cell growth as a consequence of G2/M arrest. Oral administration of LXY6006 significantly inhibited growth of breast, lung, and pancreatic tumors implanted in nude mice. These results indicate that LXY6006 represents a novel class of agents targeting a broad range of human cancers.
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    ABSTRACT: We investigated the in vitro effects of p-coumaric acid on melanogenesis. The melanin content in B16F1 cells stimulated with p-coumaric acid significantly decreased (68 % vs. control) through inhibition of tyrosinase enzyme activity assessed using both cell-free and cell-based assays (46 and 27 % compared with control, respectively). In addition, stimulating B16F1 cells with p-coumaric acid reduced cyclic adenosine monophosphate (cAMP)—responsive element-binding protein (CREB) protein phosphorylation (26 % vs. control), which in turn downregulated the expression of the microphthalmia-associated transcription factor (MITF) and its target gene tyrosinase (27 and 20 % vs. control, respectively). p-Coumaric acid has a hypopigmentation effect in melanocytes by both directly inhibiting tyrosinase enzyme activity and reducing CREB phosphorylation, which inhibits MITF and tyrosinase expression.
    European Food Research and Technology 12/2012; 235(6). DOI:10.1007/s00217-012-1830-8 · 1.39 Impact Factor

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