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

Hwa Dong Lee, Won Hee Lee, Eunmiri Roh, Chang Seob Seo, Jong Keun Son, Seung Ho Lee, Bang Yeon Hwang, Sang Hun Jung, Sang Bae Han, Youngsoo Kim

Research output: Contribution to journalLetterpeer-review

20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)761-763
Number of pages3
JournalExperimental Dermatology
Volume20
Issue number9
DOIs
StatePublished - Sep 2011

Keywords

  • Antimelanogenic activity
  • CAMP-responsive element binding protein
  • Manassantin A
  • Microphthalmia-associated transcription factor
  • Tyrosinase

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