Biotechnology Letters

, Volume 34, Issue 5, pp 805–812 | Cite as

Momilactione B inhibits protein kinase A signaling and reduces tyrosinase-related proteins 1 and 2 expression in melanocytes

  • Ji Hae Lee
  • Boram Cho
  • Hee-jin Jun
  • Woo-Duck Seo
  • Dong-Woo Kim
  • Kang-Jin Cho
  • Sung-Joon LeeEmail author
Original Research Paper


Momilactone B (MB) is a terpenoid phytoalexin present in rice bran that exhibits several biological activities. MB reduced the melanin content in B16 melanocytes melanin content and inhibited tyrosinase activities. Using transcriptome analysis, the genes involved in protein kinase A (PKA) signaling were found to be markedly altered. B16 cells stimulated with MB had decreased concentrations of cAMP protein kinase A activity, and cAMP-response element-binding protein which is a key transcription factor for microphthalmia-associated transcription factor (MITF) expression. Accordingly, the expression of MITF and its target genes, which are essential for melanogenesis, were reduced. MB thus exhibits anti-melanogenic effects by repressing tyrosinase enzyme activity and inhibiting the PKA signaling pathway which, in turn, decreases melanogenic gene expression.


Momilactone B Melanogenesis Protein kinase A Tyrosinase 



This work was carried out with the support of “Cooperative Research Program for Agriculture Science & Technology Development (Project No. PJ007480)” Rural Development Administration, Republic of Korea.


  1. Beckman KB, Lee KY, Golden T, Melov S (2004) Gene expression profiling in mitochondrial disease: assessment of microarray accuracy by high-throughput Q-PCR. Mitochondrion 4:453–470PubMedCrossRefGoogle Scholar
  2. Chakraborty AK, Funasaka Y, Komoto M, Ichihashi M (1998) Effect of arbutin on melanogenic proteins in human melanocytes. Pigment Cell Res 11:206–212PubMedCrossRefGoogle Scholar
  3. Choi YM, Jun HJ, Dawson K, Rodriguez RL, Roh MR, Jun J et al (2010) Effects of the isoflavone puerarin and its glycosides on melanogenesis in B16 melanocytes. Eur Food Res Technol 231:75–83CrossRefGoogle Scholar
  4. Chung MJ, Sung NJ, Park CS, Kweon DK, Mantovani A, Moon TW et al (2008) Antioxidative and hypocholesterolemic activities of water-soluble puerarin glycosides in HepG2 cells and in C57 BL/6 J mice. Eur J Pharmacol 578:159–170PubMedCrossRefGoogle Scholar
  5. Chung SY, Seo YK, Park JM, Seo MJ, Park JK, Kim JW et al (2009) Fermented rice bran downregulates MITF expression and leads to inhibition of alpha-MSH-induced melanogenesis in B16F1 melanoma. Biosci Biotechnol Biochem 73:1704–1710PubMedCrossRefGoogle Scholar
  6. Costin GE, Hearing VJ (2007) Human skin pigmentation: melanocytes modulate skin color in response to stress. FASEB J 21:976–994PubMedCrossRefGoogle Scholar
  7. del Marmol V, Beermann F (1996) Tyrosinase and related proteins in mammalian pigmentation. FEBS Lett 381:165–168PubMedCrossRefGoogle Scholar
  8. Huber WE, Price ER, Widlund HR, Du JY, Davis IJ, Wegner M et al (2003) A tissue-restricted cAMP transcriptional response—SOX10 modulates alpha-melanocyte-stimulating hormone-triggered expression of microphthalmia-associated transcription factor in melanocytes. J Biol Chem 278:45224–45230PubMedCrossRefGoogle Scholar
  9. Iwata M, Corn T, Iwata S, Everett MA, Fuller BB (1990) The relationship between tyrosinase activity and skin color in human foreskins. J Invest Dermatol 95:9–15PubMedCrossRefGoogle Scholar
  10. Kato T, Kabuto C, Sasaki N, Tsunagaw M, Aizawa H, Fujita K et al (1973) Momilactones, growth inhibitors from rice, Oryza-sativa L. Tetrahedron Lett 39:3861–3864CrossRefGoogle Scholar
  11. Kim SJ, Park HR, Park E, Lee SC (2007) Cytotoxic and antitumor activity of momilactone B from rice hulls. J Agric Food Chem 55:1702–1706PubMedCrossRefGoogle Scholar
  12. Kim DS, Park SH, Lee HK, Choo SJ, Lee JH, Song GY et al (2010) Hypopigmentary action of dihydropyranocoumarin D2, a decursin derivative, as a MITF-degrading agent. J Nat Prod 73:797–800PubMedCrossRefGoogle Scholar
  13. Lee JH, Jun HJ, Jia Y, Kim W, Choi SG, Lee SJ (2011a) Critical role of peroxisome proliferator activated receptor-delta on body fat reduction in C57BL/6 J and human apolipoprotein E2 transgenic mice fed delipidated soybean. J Agric Food Chem 59(21):11872–11881PubMedCrossRefGoogle Scholar
  14. Lee SJ, Jun HJ, Roh M, Kim HW, Houng SJ, Cho B et al (2011b) Dual inhibitions of lemon balm (Melissa officinalis) ethanolic extract on melanogenesis in B16-F1 murine melanocytes: inhibition of tyrosinase activity and its gene expression. Food Sci Biotechnol 20:1051–1059CrossRefGoogle Scholar
  15. Lerner AB, Fitzpatrick TB (1950) Biochemistry of melanin formation. Physiol Rev 30:91–126PubMedGoogle Scholar
  16. Levy C, Khaled M, Fisher DE (2006) MITF: master regulator of melanocyte development and melanoma oncogene. Trends Mol Med 12:406–414PubMedCrossRefGoogle Scholar
  17. Maeda K, Fukuda M (1996) Arbutin: mechanism of its depigmenting action in human melanocyte culture. J Pharmacol Exp Ther 276:765–769PubMedGoogle Scholar
  18. Morey JS, Ryan JC, Van Dolah FM (2006) Microarray validation: factors influencing correlation between oligonucleotide microarrays and real-time PCR. Biol Proced Online 8:175–193PubMedCrossRefGoogle Scholar
  19. Park HM, Lee JH, Yaoyao J, Jun HJ, Lee SJ (2011) Limonene, a natural cyclic terpene, is an agonistic ligand for adenosine A(2A) receptors. Biochem Biophys Res Commun 404:345–348PubMedCrossRefGoogle Scholar
  20. Steingrimsson E, Copeland NG, Jenkins NA (2004) Melanocytes and the microphthalmia transcription factor network. Annu Rev Genet 38:365–411PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Ji Hae Lee
    • 1
  • Boram Cho
    • 1
  • Hee-jin Jun
    • 1
  • Woo-Duck Seo
    • 2
  • Dong-Woo Kim
    • 3
  • Kang-Jin Cho
    • 4
  • Sung-Joon Lee
    • 1
    Email author
  1. 1.Division of Food Bioscience and Technology, College of Life Sciences and BiotechnologyKorea UniversitySeoulRepublic of Korea
  2. 2.Department of Functional CropNational Institute of Crop ScienceMiryangRepublic of Korea
  3. 3.Research CenterNatural F & O Corp.ChuncheonRepublic of Korea
  4. 4.Food Nutrition and Functionality Division, Department of Agrofood ResourcesNational Academy of Agricultural ScienceSuwonRepublic of Korea

Personalised recommendations