Advertisement

Archives of Dermatological Research

, Volume 303, Issue 10, pp 737–744 | Cite as

Aromatic-turmerone inhibits α-MSH and IBMX-induced melanogenesis by inactivating CREB and MITF signaling pathways

  • Sun Young Park
  • Mei Ling Jin
  • Young Hun Kim
  • YoungHee Kim
  • Sang-Joon Lee
Original Paper

Abstract

This study investigated the anti-melanogenic effect of aromatic (ar)-turmerone on alpha-melanocyte stimulating hormone (α-MSH) and 3-isobuty-1-methxlzanthine (IBMX)-induced tyrosinase (Tyr), tyrosinase-related protein 1 (TRP-1), and tyrosinase-related protein 2 (TRP-2) expression in B16F10 melanoma cells. We demonstrated that ar-turmerone inhibits α-MSH and IBMX-induced melanin synthesis and tyrosinase activity. Data also showed that ar-turmerone inhibits the expression of tyrosinase, TRP-1, and TRP-2 in α-MSH- and IBMX-stimulated B16F10 cells. In addition, ar-turmerone exhibits stronger anti-melanogenic effects than curcumin. Furthermore, ar-turmerone strongly inhibited α-MSH- and IBMX-induced microphthalmia-associated transcription factor by suppressing the activity of cyclic adenosine monophosphate (cAMP)-responsive element binding protein in α-MSH-stimulated B16F10 cells. Our data revealed that ar-turmerone is a novel, effective, anti-melanogenic agent that functions by downregulating tyrosinase, Trp-1, and Trp-2 gene expression. Therefore, ar-turmerone may be a useful therapeutic agent for treating hyperpigmentation disorders, such as freckles and melasma, and as a beneficial additive in whitening cosmetics.

Keywords

Ar-turmerone Melanin Tyrosinase cAMP-responsive element binding protein (CREB) Microphthalmia-associated transcription factor (MITF) 

References

  1. 1.
    Aggarwal BB, Harikumar KB (2009) Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol 41:40–59PubMedCrossRefGoogle Scholar
  2. 2.
    Ahn SJ, Koketsu M, Ishihara H, Lee SM, Ha SK, Lee KH, Kang TH, Kima SY (2006) Regulation of melanin synthesis by selenium-containing carbohydrates. Chem Pharm Bull (Tokyo) 54:281–286CrossRefGoogle Scholar
  3. 3.
    Bentley NJ, Eisen T, Goding CR (1994) Melanocyte-specific expression of the human tyrosinase promoter: activation by the microphthalmia gene product and role of the initiator. Mol Cell Biol 14:7996–8006PubMedGoogle Scholar
  4. 4.
    Bertolotto C, Abbe P, Hemesath TJ, Bille K, Fisher DE, Ortonne JP, Ballotti R (1998) Microphthalmia gene product as a signal transducer in cAMP-induced differentiation of melanocytes. J Cell Biol 142:827–835PubMedCrossRefGoogle Scholar
  5. 5.
    Boissy RE (2003) Melanosome transfer to and translocation in the keratinocyte. Exp Dermatol 12(Suppl 2):5–12PubMedCrossRefGoogle Scholar
  6. 6.
    Busca R, Bertolotto C, Ortonne JP, Ballotti R (1996) Inhibition of the phosphatidylinositol 3-kinase/p70(S6)-kinase pathway induces B16 melanoma cell differentiation. J Biol Chem 271:31824–31830PubMedCrossRefGoogle Scholar
  7. 7.
    Chakraborty AK, Funasaka Y, Slominski A, Ermak G, Hwang J, Pawelek JM, Ichihashi M (1996) Production and release of proopiomelanocortin (POMC) derived peptides by human melanocytes and keratinocytes in culture: regulation by ultraviolet B. Biochim Biophys Acta 1313:130–138PubMedCrossRefGoogle Scholar
  8. 8.
    Costin GE, Hearing VJ (2007) Human skin pigmentation: melanocytes modulate skin color in response to stress. FASEB J 21:976–994PubMedCrossRefGoogle Scholar
  9. 9.
    Eller MS, Ostrom K, Gilchrest BA (1996) DNA damage enhances melanogenesis. Proc Natl Acad Sci USA 93:1087–1092PubMedCrossRefGoogle Scholar
  10. 10.
    Eves PC, MacNeil S, Haycock JW (2006) Alpha-melanocyte stimulating hormone, inflammation and human melanoma. Peptides 27:444–452PubMedCrossRefGoogle Scholar
  11. 11.
    Gescher A (2004) Polyphenolic phytochemicals versus non-steroidal anti-inflammatory drugs: which are better cancer chemopreventive agents? J Chemother 16(Suppl 4):3–6PubMedGoogle Scholar
  12. 12.
    Goding CR (2000) Mitf from neural crest to melanoma: signal transduction and transcription in the melanocyte lineage. Genes Dev 14:1712–1728PubMedGoogle Scholar
  13. 13.
    Ha SK, Koketsu M, Lee K, Choi SY, Park JH, Ishihara H, Kim SY (2005) Inhibition of tyrosinase activity by N,N-unsubstituted selenourea derivatives. Biol Pharm Bull 28:838–840PubMedCrossRefGoogle Scholar
  14. 14.
    Halaban R, Pomerantz SH, Marshall S, Lerner AB (1984) Tyrosinase activity and abundance in cloudman melanoma cells. Arch Biochem Biophys 230:383–387PubMedCrossRefGoogle Scholar
  15. 15.
    Hatcher H, Planalp R, Cho J, Torti FM, Torti SV (2008) Curcumin: from ancient medicine to current clinical trials. Cell Mol Life Sci 65:1631–1652PubMedCrossRefGoogle Scholar
  16. 16.
    Hunt G, Todd C, Cresswell JE, Thody AJ (1994) Alpha-melanocyte stimulating hormone and its analogue Nle4DPhe7 alpha-MSH affect morphology, tyrosinase activity and melanogenesis in cultured human melanocytes. J Cell Sci 107(Pt 1):205–211PubMedGoogle Scholar
  17. 17.
    Jang JY, Lee JH, Jeong SY, Chung KT, Choi YH, Choi BT (2009) Partially purified Curcuma longa inhibits alpha-melanocyte-stimulating hormone-stimulated melanogenesis through extracellular signal-regulated kinase or Akt activation-mediated signalling in B16F10 cells. Exp Dermatol 18:689–694PubMedCrossRefGoogle Scholar
  18. 18.
    Jung E, Lee J, Huh S, Lee J, Kim YS, Kim G, Park D (2009) Phloridzin-induced melanogenesis is mediated by the cAMP signaling pathway. Food Chem Toxicol 47:2436–2440PubMedCrossRefGoogle Scholar
  19. 19.
    Kadekaro AL, Kavanagh RJ, Wakamatsu K, Ito S, Pipitone MA, Abdel-Malek ZA (2003) Cutaneous photobiology. The melanocyte vs. the sun: who will win the final round? Pigment Cell Res 16:434–447PubMedCrossRefGoogle Scholar
  20. 20.
    Kanwar AJ, Dhar S, Kaur S (1994) Treatment of melasma with potent topical corticosteroids. Dermatology 188:170PubMedCrossRefGoogle Scholar
  21. 21.
    Kubo I, Kinst-Hori I, Chaudhuri SK, Kubo Y, Sanchez Y, Ogura T (2000) Flavonols from Heterotheca inuloides: tyrosinase inhibitory activity and structural criteria. Bioorg Med Chem 8:1749–1755PubMedCrossRefGoogle Scholar
  22. 22.
    Mas JS, Gerritsen I, Hahmann C, Jimenez-Cervantes C, Garcia-Borron JC (2003) Rate limiting factors in melanocortin 1 receptor signalling through the cAMP pathway. Pigment Cell Res 16:540–547PubMedCrossRefGoogle Scholar
  23. 23.
    Mountjoy KG, Robbins LS, Mortrud MT, Cone RD (1992) The cloning of a family of genes that encode the melanocortin receptors. Science 257:1248–1251PubMedCrossRefGoogle Scholar
  24. 24.
    Ohguchi K, Ito M, Yokoyama K, Iinuma M, Itoh T, Nozawa Y, Akao Y (2009) Effects of sesquiterpene lactones on melanogenesis in mouse B16 melanoma cells. Biol Pharm Bull 32:308–310PubMedCrossRefGoogle Scholar
  25. 25.
    Perez-Gilabert M, Garcia-Carmona F (2001) Dimethyl sulfide, a volatile flavor constituent, is a slow-binding inhibitor of tyrosinase. Biochem Biophys Res Commun 285:257–261PubMedCrossRefGoogle Scholar
  26. 26.
    Riley PA (2003) Melanogenesis and melanoma. Pigment Cell Res 16:548–552PubMedCrossRefGoogle Scholar
  27. 27.
    Roh JS, Han JY, Kim JH, Hwang JK (2004) Inhibitory effects of active compounds isolated from safflower (Carthamus tinctorius L.) seeds for melanogenesis. Biol Pharm Bull 27:1976–1978PubMedCrossRefGoogle Scholar
  28. 28.
    Sassone-Corsi P (1995) Transcription factors responsive to cAMP. Annu Rev Cell Dev Biol 11:355–377PubMedCrossRefGoogle Scholar
  29. 29.
    Unver N, Freyschmidt-Paul P, Horster S, Wenck H, Stab F, Blatt T, Elsasser HP (2006) Alterations in the epidermal-dermal melanin axis and factor XIIIa melanophages in senile lentigo and ageing skin. Br J Dermatol 155:119–128PubMedCrossRefGoogle Scholar
  30. 30.
    Virador V, Matsunaga N, Matsunaga J, Valencia J, Oldham RJ, Kameyama K, Peck GL, Ferrans VJ, Vieira WD, Abdel-Malek ZA, Hearing VJ (2001) Production of melanocyte-specific antibodies to human melanosomal proteins: expression patterns in normal human skin and in cutaneous pigmented lesions. Pigment Cell Res 14:289–297PubMedCrossRefGoogle Scholar
  31. 31.
    Wong G, Pawelek J (1975) Melanocyte-stimulating hormone promotes activation of pre-existing tyrosinase molecules in cloudman S91 melanoma cells. Nature 255:644–646PubMedCrossRefGoogle Scholar
  32. 32.
    Yang JY, Koo JH, Song YG, Kwon KB, Lee JH, Sohn HS, Park BH, Jhee EC, Park JW (2006) Stimulation of melanogenesis by scoparone in B16 melanoma cells. Acta Pharmacol Sin 27:1467–1473PubMedCrossRefGoogle Scholar
  33. 33.
    Yasumoto K, Yokoyama K, Takahashi K, Tomita Y, Shibahara S (1997) Functional analysis of microphthalmia-associated transcription factor in pigment cell-specific transcription of the human tyrosinase family genes. J Biol Chem 272:503–509PubMedCrossRefGoogle Scholar
  34. 34.
    Yokota T, Nishio H, Kubota Y, Mizoguchi M (1998) The inhibitory effect of glabridin from licorice extracts on melanogenesis and inflammation. Pigment Cell Res 11:355–361PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Sun Young Park
    • 1
  • Mei Ling Jin
    • 3
  • Young Hun Kim
    • 1
  • YoungHee Kim
    • 2
  • Sang-Joon Lee
    • 3
  1. 1.Bio-IT Fusion Technology Research InstitutePusan National UniversityBusanRepublic of Korea
  2. 2.Department of Molecular BiologyPusan National UniversityBusanRepublic of Korea
  3. 3.Department of MicrobiologyPusan National UniversityBusanRepublic of Korea

Personalised recommendations