Sargaquinoic acid ameliorates hyperpigmentation through cAMP and ERK-mediated downregulation of MITF in α-MSH-stimulated B16F10 cells

[Display omitted] •Sargaquinoic acid (SQA) inhibits melanin synthesis in B16F10 mouse melanoma cells.•SQA inhibits cAMP production and block cAMP binding to protein kinase A.•SQA suppresses tyrosinase and TRPs via cAMP/CREB-mediated downregulation of MITF.•SQA activates ERK1/2 leading to the proteas...

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Bibliographic Details
Published in:Biomedicine & pharmacotherapy 2018-08, Vol.104, p.582-589
Main Authors: Azam, Mohammed Shariful, Kwon, Misung, Choi, Jinkyung, Kim, Hyeung-Rak
Format: Article
Language:English
Subjects:
cAMP
ERK
Hyperpigmentation
MITF
Sargaquinoic acid
Tyrosinase
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Summary:[Display omitted] •Sargaquinoic acid (SQA) inhibits melanin synthesis in B16F10 mouse melanoma cells.•SQA inhibits cAMP production and block cAMP binding to protein kinase A.•SQA suppresses tyrosinase and TRPs via cAMP/CREB-mediated downregulation of MITF.•SQA activates ERK1/2 leading to the proteasomal degradation of MITF.•SQA could be used for cosmetic therapy against skin hyperpigmentation disorders. Hyperpigmentation disorders of the skin adversely influence the quality of life. We previously demonstrated the hypopigmenting properties of the ethanolic extract from Sargassum serratifolium and identified sargaquinoic acid (SQA) as an active component. The current study aims to investigate the hypopigmenting action of SQA in α-melanocyte stimulating hormone (α-MSH)-stimulated B16F10 cells. SQA attenuated cellular melanin synthesis by inhibiting the expression of the melanogenic enzymes, including tyrosinase (TYR), tyrosinase-related protein 1 (TRP1), and TRP2. SQA also inhibited cellular TYR activity in a dose-dependent manner. Reduced intracellular cAMP accumulation by SQA treatment resulted in the suppressed phosphorylation of cAMP-responsive element-binding protein (CREB), leading to the downregulation of microphthalmia-associated transcription factor (MITF) in α-MSH-stimulated B16F10 cells. SQA increased the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and MITF (Ser73), inducing proteasomal degradation of MITF. SQA showed high binding affinity to the cAMP binding domain of PKA; the direct binding of SQA to PKA may exert an additional inhibitory effect on the PKA-dependent CREB activation. Our data demonstrated that SQA suppressed melanin production through the cAMP/CREB- and ERK1/2-mediated downregulation of MITF in α-MSH-stimulated B16F10 cells and SQA has a potential therapeutic agent for the treatment of skin hyperpigmentation disorders.
ISSN:0753-3322
1950-6007
DOI:10.1016/j.biopha.2018.05.083