4-(Phenylsulfanyl)butan-2-One Suppresses Melanin Synthesis and Melanosome Maturation In Vitro and In Vivo

In this study, we screened compounds with skin whitening properties and favorable safety profiles from a series of marine related natural products, which were isolated from Formosan soft coral Cladiella australis. Our results indicated that 4-(phenylsulfanyl)butan-2-one could successfully inhibit pigment generation processes in mushroom tyrosinase platform assay, probably through the suppression of tyrosinase activity to be a non-competitive inhibitor of tyrosinase. In cell-based viability examinations, it demonstrated low cytotoxicity on melanoma cells and other normal human cells. It exhibited stronger inhibitions of melanin production and tyrosinase activity than arbutin or 1-phenyl-2-thiourea (PTU). Also, we discovered that 4-(phenylsulfanyl)butan-2-one reduces the protein expressions of melanin synthesis-related proteins, including the microphthalmia-associated transcription factor (MITF), tyrosinase-related protein-1 (Trp-1), dopachrome tautomerase (DCT, Trp-2), and glycoprotein 100 (GP100). In an in vivo zebrafish model, it presented a remarkable suppression in melanogenesis after 48 h. In summary, our in vitro and in vivo biological assays showed that 4-(phenylsulfanyl)butan-2-one possesses anti-melanogenic properties that are significant in medical cosmetology.

[1]  C. Cohen,et al.  Key Regulatory Role of Dermal Fibroblasts in Pigmentation as Demonstrated Using a Reconstructed Skin Model: Impact of Photo-Aging , 2014, PloS one.

[2]  M. Baptista,et al.  Melanin Photosensitization and the Effect of Visible Light on Epithelial Cells , 2014, PloS one.

[3]  D. Hwang,et al.  Hyperosmotic Stress Reduces Melanin Production by Altering Melanosome Formation , 2014, PloS one.

[4]  Shi-Ying Huang,et al.  Flexibilide Obtained from Cultured Soft Coral Has Anti-Neuroinflammatory and Analgesic Effects through the Upregulation of Spinal Transforming Growth Factor-β1 in Neuropathic Rats , 2014, Marine drugs.

[5]  Shi-Ying Huang,et al.  Effects of 6-hydroxydopamine exposure on motor activity and biochemical expression in zebrafish (Danio rerio) larvae. , 2014, Zebrafish.

[6]  M. Ho,et al.  Correction: Novel Biodegradable Porous Scaffold Applied to Skin Regeneration , 2013, PLoS ONE.

[7]  A. Giordano,et al.  The zebrafish as a model for nociception studies , 2013, Journal of cellular physiology.

[8]  C. Chiu,et al.  Alpinia oxyphylla Miq. bioactive extracts from supercritical fluid carbon dioxide extraction , 2013 .

[9]  Chao-Ling Yao,et al.  Inhibitory effect of ectoine on melanogenesis in B16-F0 and A2058 melanoma cell lines , 2013 .

[10]  Po-Len Liu,et al.  Antimelanoma and Antityrosinase from Alpinia galangal Constituents , 2013, TheScientificWorldJournal.

[11]  Z. Wen,et al.  Biofunctional Constituents from Liriodendron tulipifera with Antioxidants and Anti-Melanogenic Properties , 2013, International journal of molecular sciences.

[12]  Shi-Ying Huang,et al.  Sinularin from Indigenous Soft Coral Attenuates Nociceptive Responses and Spinal Neuroinflammation in Carrageenan-Induced Inflammatory Rat Model , 2012, Marine drugs.

[13]  Blazej Zbytek,et al.  Sensing the environment: regulation of local and global homeostasis by the skin's neuroendocrine system. , 2012, Advances in anatomy, embryology, and cell biology.

[14]  Hui-Chun Wang,et al.  Biological Properties of Acidic Cosmetic Water from Seawater , 2012, International journal of molecular sciences.

[15]  Chien-Chih Chiu,et al.  Bio-Functional Constituents from the Stems of Liriodendron tulipifera , 2012, Molecules.

[16]  A. Slominski,et al.  L‐tyrosine and L‐dihydroxyphenylalanine as hormone‐like regulators of melanocyte functions , 2012, Pigment cell & melanoma research.

[17]  Shi-Ying Huang,et al.  Neuroprotection by marine-derived compound, 11-dehydrosinulariolide, in an in vitro Parkinson’s model: a promising candidate for the treatment of Parkinson’s disease , 2012, Naunyn-Schmiedeberg's Archives of Pharmacology.

[18]  Shi-Ying Huang,et al.  Intrathecal lemnalol, a natural marine compound obtained from Formosan soft coral, attenuates nociceptive responses and the activity of spinal glial cells in neuropathic rats , 2011, Behavioural pharmacology.

[19]  Yu-chen Chang,et al.  Bioconstituents from stems of Synsepalum dulcificum Daniell (Sapotaceae) inhibit human melanoma proliferation, reduce mushroom tyrosinase activity and have antioxidant properties , 2011 .

[20]  Z. Wen,et al.  Identifying melanogenesis inhibitors from Cinnamomum subavenium with in vitro and in vivo screening systems by targeting the human tyrosinase , 2011, Experimental dermatology.

[21]  Z. Wen,et al.  A neuroprotective sulfone of marine origin and the in vivo anti-inflammatory activity of an analogue. , 2010, European journal of medicinal chemistry.

[22]  Chung-Yi Chen,et al.  (-)-N-Formylanonaine from Michelia alba as a human tyrosinase inhibitor and antioxidant. , 2010, Bioorganic & medicinal chemistry.

[23]  M. V. Schiaffino Signaling pathways in melanosome biogenesis and pathology. , 2010, The international journal of biochemistry & cell biology.

[24]  Jo-Shu Chang,et al.  Tyrosinase inhibition, free radical scavenging, antimicroorganism and anticancer proliferation activities of Sapindus mukorossi extracts , 2010 .

[25]  Shi-Ying Huang,et al.  Capnellene, a natural marine compound derived from soft coral, attenuates chronic constriction injury‐induced neuropathic pain in rats , 2009, British journal of pharmacology.

[26]  D. Tobin,et al.  The silver locus product (Silv/gp100/Pmel17) as a new tool for the analysis of melanosome transfer in human melanocyte–keratinocyte co‐culture , 2008, Experimental dermatology.

[27]  Woo-Sik Kim,et al.  Design of optimal solvent for extraction of bio-active ingredients from mulberry leaves , 2007 .

[28]  Cheol‐Hee Kim,et al.  Zebrafish as a new model for phenotype-based screening of melanogenic regulatory compounds. , 2007, Pigment cell research.

[29]  M. Ichihashi,et al.  Approaches to identify inhibitors of melanin biosynthesis via the quality control of tyrosinase. , 2007, The Journal of investigative dermatology.

[30]  I. Jackson,et al.  Regulation of pigmentation in zebrafish melanophores. , 2006, Pigment cell research.

[31]  Sun-Long Cheng,et al.  Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. , 2006, Biological & pharmaceutical bulletin.

[32]  G. Raposo,et al.  The Silver locus product Pmel17/gp100/Silv/ME20: controversial in name and in function. , 2005, Pigment cell research.

[33]  V. Hearing,et al.  MART-1 Is Required for the Function of the Melanosomal Matrix Protein PMEL17/GP100 and the Maturation of Melanosomes* , 2005, Journal of Biological Chemistry.

[34]  Donald R Love,et al.  Technology for high-throughput screens: the present and future using zebrafish. , 2004, Current opinion in biotechnology.

[35]  D. Tobin,et al.  Melanin pigmentation in mammalian skin and its hormonal regulation. , 2004, Physiological reviews.

[36]  R. Kelsh Genetics and evolution of pigment patterns in fish. , 2004, Pigment cell research.

[37]  S. Kitajima,et al.  Effects of kojic acid on thyroidal functions in rats by single-dose administration and in cultured rat thyroid cells (FRTL-5 cells). , 2002, The Journal of toxicological sciences.

[38]  D. Fisher,et al.  Microphthalmia Gene Product as a Signal Transducer in cAMP-Induced Differentiation of Melanocytes , 1998, The Journal of cell biology.

[39]  K Takahashi,et al.  Functional Analysis of Microphthalmia-associated Transcription Factor in Pigment Cell-specific Transcription of the Human Tyrosinase Family Genes* , 1997, The Journal of Biological Chemistry.

[40]  C. Nüsslein-Volhard,et al.  Zebrafish pigmentation mutations and the processes of neural crest development. , 1996, Development.

[41]  James A. Vaught,et al.  microphthalmia, a critical factor in melanocyte development, defines a discrete transcription factor family. , 1994, Genes & development.

[42]  M. K. Jacobsohn,et al.  Incorporation and binding of estrogens into melanin: comparison of mushroom and mammalian tyrosinases. , 1992, Biochimica et biophysica acta.

[43]  A. Slominski,et al.  L-tyrosine, L-dopa, and tyrosinase as positive regulators of the subcellular apparatus of melanogenesis in Bomirski Ab amelanotic melanoma cells. , 1989, Pigment cell research.

[44]  G. Schütz,et al.  Functional analysis of alternatively spliced tyrosinase gene transcripts. , 1988, The EMBO journal.

[45]  A. Slominski,et al.  Positive regulation of melanin pigmentation by two key substrates of the melanogenic pathway, L-tyrosine and L-dopa. , 1988, Journal of cell science.