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Melanogenesis-inducing effect of cirsimaritin through increases in microphthalmia-associated transcription factor and tyrosinase expression.

Abstract
The melanin-inducing properties of cirsimaritin were investigated in murine B16F10 cells. Cirsimaritin is an active flavone with methoxy groups, which is isolated from the branches of Lithocarpus dealbatus. Tyrosinase activity and melanin content in murine B16F10 melanoma cells were increased by cirsimaritin in a dose-dependent manner. Western blot analysis revealed that tyrosinase, tyrosinase-related protein (TRP) 1, TRP2 protein levels were enhanced after treatment with cirsimaritin for 48 h. Cirsimaritin also upregulated the expression of microphthalmia-associated transcription factor (MITF) after 24 h of treatment. Furthermore, cirsimaritin induced phosphorylation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) in a dose-dependent manner after treatment for 15 min. The cirsimaritin-mediated increase of tyrosinase activity was significantly attenuated by H89, a cAMP-dependent protein kinase A inhibitor. These findings indicate that cirsimaritin stimulates melanogenesis in B16F10 cells by activation of CREB as well as upregulation of MITF and tyrosinase expression, which was activated by cAMP signaling. Finally, the melanogenic effect of cirsimaritin was confirmed in human epidermal melanocytes. These results support the putative application of cirsimaritin in ultraviolet photoprotection and hair coloration treatments.
AuthorsHyo Jung Kim, Il Soon Kim, Yin Dong, Ik-Soo Lee, Jin Sook Kim, Jong-Sang Kim, Je-Tae Woo, Byung-Yoon Cha
JournalInternational journal of molecular sciences (Int J Mol Sci) Vol. 16 Issue 4 Pg. 8772-88 (Apr 20 2015) ISSN: 1422-0067 [Electronic] Switzerland
PMID25903150 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Creb1 protein, mouse
  • Cyclic AMP Response Element-Binding Protein
  • Flavones
  • Melanins
  • Membrane Glycoproteins
  • Microphthalmia-Associated Transcription Factor
  • Mitf protein, mouse
  • cirsimaritin
  • Cyclic AMP
  • Oxidoreductases
  • Tyrp1 protein, mouse
  • Monophenol Monooxygenase
  • Cyclic AMP-Dependent Protein Kinases
  • Intramolecular Oxidoreductases
  • dopachrome isomerase
Topics
  • Animals
  • Cell Survival
  • Cyclic AMP (metabolism)
  • Cyclic AMP Response Element-Binding Protein (metabolism)
  • Cyclic AMP-Dependent Protein Kinases (metabolism)
  • Flavones (pharmacology)
  • Humans
  • Intramolecular Oxidoreductases (metabolism)
  • Melanins (biosynthesis)
  • Melanocytes (drug effects, metabolism)
  • Melanoma, Experimental
  • Membrane Glycoproteins (metabolism)
  • Mice
  • Microphthalmia-Associated Transcription Factor (metabolism)
  • Monophenol Monooxygenase
  • Oxidoreductases (metabolism)
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Second Messenger Systems
  • Up-Regulation (drug effects)

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