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

• Published in: Experimental dermatology Vol. 20; no. 9; pp. 761 - 763
• Main Authors: Lee, Hwa Dong, Lee, Won-Hee, Roh, Eunmiri, Seo, Chang-Seob, Son, Jong-Keun, Lee, Seung Ho, Hwang, Bang Yeon, Jung, Sang-Hun, Han, Sang-Bae, Kim, Youngsoo
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.09.2011; Blackwell
• Subjects: Animals; antimelanogenic activity; Biological and medical sciences; cAMP-responsive element binding protein; Cell Line; Cell Line, Tumor; Cyclic AMP - pharmacology; Dermatology; Down-Regulation - drug effects; Lignans - pharmacology; Malformations of the eye; manassantin A; Medical sciences; Melanins - biosynthesis; Melanocytes - drug effects; Melanocytes - metabolism; Melanoma, Experimental - drug therapy; Melanoma, Experimental - genetics; Melanoma, Experimental - metabolism; Mice; microphthalmia-associated transcription factor; Microphthalmia-Associated Transcription Factor - genetics; Monophenol Monooxygenase - genetics; Ophthalmology; tyrosinase; Dermatology; Gene expression; cAMP; tyrosinase; Congenital disease; Binding protein; microphthalmia-associated transcription factor; Eye disease; antimelanogenic activity; responsive element binding protein; Malformation; Risk factor; manassantin A; Transcription factor; Melanin; Microphthalmia
• ISSN: 0906-6705; 1600-0625
• DOI: 10.1111/j.1600-0625.2011.01296.x

:  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.