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

Abstract

hair fibre, as protein extracts of the hair shaft analysed by mass spectroscopy following separation by gel electrophoresis showed certain age-dependent differences in the peptide pattern (data not shown). Further studies will show whether those alterations can explain the macroscopic changes of mature hair and how they influence the mechanical behaviour. Acknowledgements We thank Ms. Sabine Gruedl for her technical assistance and the analysis of parts of the data sets. Mr. Olaf Holtkoetter contributes to the analysis of the microarray data sets. Mr. Guido Fuhrmann supported the sample collection and preparation of the samples. Mrs. Andrea Koerner was responsible for the analysis of hair fibres using mass spectroscopy techniques and Mr. Dirk Petersohn revised and approved the manuscript. Mrs. Melanie Giesen designed the study, analysed parts of the data sets and wrote the paper. Conflict of interest The authors state no conflict of interest. References 1 Trü eb R M. J Cosmet Dermatol 2005: 4: 60-72. 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.

A Synthetic Manassantin A Derivative Inhibits Hypoxia-Inducible Factor 1 and Tumor Growth

“…Indeed, manassantin A has been reported to affect expression of a variety of genes ( e.g. , ICAM-1, MITF), and is also known to suppress the NF-κB transcriptional activity [23], [24]. Interestingly, manassantin A was also reported to inhibit activation of multiple signaling pathways such as pathways mediated by ERK, p38, JNK and STAT3 [25], [26].…”

Inhibitory effect of liposome-encapsulated anthocyanin on melanogenesis in human melanocytes

“…In mammals, skin pigmentation results from the transfer of melanosomes from melanocytes to neighboring keratinocytes, which eventually darkens the skin color (Hearing, 2005;Yamaguchi & Hearing, 2009). Melanin synthesis is regulated by melanogenic enzymes, including tyrosinase and the microphthalmia-associated transcription factor (MITF) (Lee et al, 2011). Tyrosinase is a rate-limiting enzyme that catalyzes the hydroxylation of tyrosine to 3,4-dihydroxyphenylalanine (DOPA) and the oxidation of DOPA to DOPAquinone (Kim et al, 2006).…”

Discovery of Manassantin A Protein Targets Using Large-Scale Protein Folding and Stability Measurements

“…1 In cell-based assays manassantin A has been shown to possess therapeutic potential for the treatment of diseases involving melanin production, 5,6 atherosclerosis, 7–9 and cancer. 1,10–12 Manassantin A exhibits cytotoxicity against a wide range of cancer cell lines including HT-29, HepG2, PC-3, and MDA-MB-231, but weak cytotoxicity against non-cancer cell lines.…”