title: 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.forename: Hwa Dong
authors.initials: HD
authors.lastname: Lee
authors.forename: Won-Hee
authors.initials: WH
authors.lastname: Lee
authors.forename: Eunmiri
authors.initials: E
authors.lastname: Roh
authors.forename: Chang-Seob
authors.initials: CS
authors.lastname: Seo
authors.forename: Jong-Keun
authors.initials: JK
authors.lastname: Son
authors.forename: Seung Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Bang Yeon
authors.initials: BY
authors.lastname: Hwang
authors.forename: Sang-Hun
authors.initials: SH
authors.lastname: Jung
authors.forename: Sang-Bae
authors.initials: SB
authors.lastname: Han
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D017705:Lignans / Q000494:pharmacology*; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics*; D014442:Monophenol Monooxygenase / Q000235:genetics*
chemical_list: D017705:Lignans; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; C054895:manassantin A; D000242:Cyclic AMP; D014442:Monophenol Monooxygenase