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

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.

• Authors: 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
• Journal: Experimental dermatology (Exp Dermatol) Vol. 20 Issue 9 Pg. 761-3 (Sep 2011) ISSN: 1600-0625 [Electronic] Denmark
• PMID: 21569106 (Publication Type: Letter, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 John Wiley & Sons A/S.

Chemical References

• Lignans
• Melanins
• Microphthalmia-Associated Transcription Factor
• Mitf protein, mouse
• manassantin A
• Cyclic AMP
• Monophenol Monooxygenase

Topics

• Animals
• Cell Line
• Cell Line, Tumor
• Cyclic AMP (pharmacology)
• Down-Regulation (drug effects)
• Lignans (pharmacology)
• Melanins (biosynthesis)
• Melanocytes (drug effects, metabolism)
• Melanoma, Experimental (drug therapy, genetics, metabolism)
• Mice
• Microphthalmia-Associated Transcription Factor (genetics)
• Monophenol Monooxygenase (genetics)