Abstract
Aim:
The effect of coumarin derivatives on melanogenesis was investigated in B16 murine melanoma cells.
Methods:
Melanin content and tyrosinase activity were analyzed spectrophotometrically. The expression of tyrosinase, tyrosinase-related protein-1 (TRP-1) and tyrosinase-related protein-2 (TRP-2) were measured either by reverse transcription-polymerase chain reaction (RT-PCR) or Western blot.
Results:
Among the coumarin derivatives studied, scoparone (6,7-dimethoxycoumarin) was the most potent; the 6- or 7-methoxy group was found to be essential for the stimulation of melanogenesis. The melanin content was greatly increased by scoparone in a dose-dependent manner; there was no cytotoxicity at the effective concentrations. Scoparone increased enzyme activity as well as protein and mRNA expression of tyrosinase. In addition, mRNA of TRP-1 and TRP-2 were also increased after treatment with scoparone. H-89, an inhibitor of protein kinase A (PKA), completely inhibited the scoparone-induced increase of melanogenesis and the tyrosinase protein.
Conclusion:
These results suggest that scoparone-induced stimulation of melanogenesis is likely to occur at the transcriptional level of melanogenesis-related enzymes through PKA signaling.
Similar content being viewed by others
Article PDF
References
Hearing VJ . Regulation of melanin formation. In: Nordlund JJ, Boissy RE, Hearing VJ, King RA, Ortonne JP, editors. The pigmentary system: physiology and pathophysiology. New York: Oxford University Press; 1998. p 423–38.
del Marmol V, Beermann F . Tyrosinase and related proteins in mammalian pigmentation. FEBS Lett 1996; 381: 165–8.
Hearing VJ, Jimenez M . Mammalian tyrosinase-the critical regulatory control point in melanocyte pigmentation. Int J Biochem 1987; 19: 1141–7.
Yokoyama K, Yasumoto K, Suzuki H, Shibahara S . Cloning of the human DOPAchrome tautomerase/tyrosinase-related protein 2 gene and identification of two regulatory regions required for its pigment cell-specific expression. J Biol Chem 1994; 269: 27080–7.
Kobayashi T, Urabe K, Winder A, Jimenez-Cervantes C, Imokawa G, Brewington T, et al. Tyrosinase related protein 1 (TRP1) functions as a DHICA oxidase in melanin biosynthesis. EMBO J 1994; 13: 5818–25.
Egan D, O'kennedy R, Moran E, Cox D, Prosser E, Thornes RD . The pharmacology, metabolism, analysis and applications of coumarin and coumarin-related compounds. Drug Metabol 1990; 22: 503–29.
Huang HC, Chu SH, Lee Chao PD . Vasorelaxants from Chinese herbs, emodin and scoparone, possess immunosuppressive properties. Eur J Pharmacol 1991; 198: 211–3.
Huang HC, Huang YL, Chang JL, Chen CC, Lee YT . Possible mechanism of immunosuppressive effect of scoparone (6,7-dimethoxycoumarin). Eur J Pharmacol 1992; 217: 143–8.
Huang HC, Lee CR, Weng YI, Lee MC, Lee YT . Vasodilator effect of scoparone (6,7-dimethoxycoumarin) from a Chinese herb. Eur J Pharmacol 1992; 218: 123–8.
Huang HC, Weng YI, Lee CR, Jan TR, Chen YL, Lee YT . Protection by scoparone against the alterations of plasma lipopro-teins, vascular morphology and vascular reactivity in hyperli-pidaemic diabetic rabbit. Br J Pharmacol 1993; 110: 1508–14.
Mennes WC, Luijckx NB, Wortelboer HM, Noordhoek J, Blaauboer BJ . Differences in the effects of model inducers of cytochrome P450 on the biotransformation of scoparone in rat and hamster liver. Arch Toxicol 1993; 67: 92–7.
Hoult JR, Paya M . Pharmacological and biochemical actions of simple coumarins: natural products with therapeutic potential. Gen Pharmacol 1996; 27: 713–22.
Ando H, Ryu A, Hashimoto A, Oka M, Ichihashi M . Linoleic acid and alpha-linolenic acid lightens ultraviolet-induced hyper-pigmentation of the skin. Arch Dematol Res 1998; 290: 375–81.
Jung GD, Yang JY, Song ES, Park JW . Stimulation of melano-genesis by glycyrrhizin in B16 melanoma cells. Exp Mol Med 2001; 33: 131–5.
Bradford MM . A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248–54.
Lerch K . Monophenol monooxygenase from Neurospora crassa. Methods Enzymol 1987; 142: 165–9.
Mosmann T . Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983; 65: 55–63.
Laemmli UK . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970; 227: 680–5.
Chijiwa T, Mishima A, Hagiwara M, Sano M, Hayashi K, Inoue T, et al. Inhibition of forskolin-induced neurite outgrowth and protein phosphorylation by a newly synthesized selective inhibitor of cyclic AMP-dependent protein kinase, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), of PC12D pheochromocytoma cells. J Biol Chem 1990; 265: 5267–72.
Nagata H, Takekoshi S, Takeyama R, Homma T, Yoshiyuki Osamura R . Quercetin enhances melanogenesis by increasing the activity and synthesis of tyrosinase in human melanoma cells and in normal human melanocytes. Pigment Cell Res 2004; 17: 66–73.
Masamoto Y, Murata Y, Baba K, Shimoishi Y, Tada M, Takahata K . Inhibitory effects of esculetin on melanin biosynthesis. Biol Pharm Bull 2004; 27: 422–5.
Hearing VJ . Biochemical control of melanogenesis and melano-somal organization. J Investig Dermatol Symp Proc 1999; 4: 24–8.
Pawelek JM, Chakraborty AK . The enzymology of melanogenesis. In: Nordlund JJ, Boissy RE, Hearing VJ, King RA, Ortonne JP, editors. The pigmentary system: physiology and pathophy-siology. New York: Oxford University Press; 1998. p 391–400.
Busca R, Ballotti R . Cyclic AMP, a key messenger in the regulation of skin pigmentation. Pigment Cell Res 2000; 13: 60–9.
Park HY, Gilchrest BA . Signaling pathways mediating melanogenesis. Cell Mol Biol 1999; 45: 919–30.
Romero-Graillet C, Aberdam E, Biagoli N, Massabni W, Ortonne JP, Ballotti R . Ultraviolet B radiation acts through the nitric oxide and cGMP sigmal transduction pathway to stimulate melanogenesis in human melanocytes. J Biol Chem 1996; 271: 28052–6.
Romero-Graillet C, Aberdam E, Clement M, Ortonne JP, Ballotti R . Nitric oxide produced by ultraviolet-irradiated keratinocytes stimulates melanogenesis. J Clin Invest 1997; 99: 635–42.
Lee J, Jung E, Park J, Jung K, Park E, Kim J, et al. Glycyrrhizin induces melanogenesis by elevating a cAMP level in B16 melanoma cells. J Invest Dermatol 2005; 124: 405–11.
Englaro W, Bahadoran P, Bertolotto C, Busca R, Derijard B, Livolsi A, et al. Tumor necrosis factor alpha-mediated inhibition of melanogenesis is dependent on nuclear factor kappa B activation. Oncogene 1999; 18: 1553–9.
Jang SI, Kim YJ, Kim HJ, Lee JC, Kim HY, Kim YC, et al. Scoparone inhibits PMA-induced IL-8 and MCP-1 production through suppression of NF-kappaB activation in U937 cells. Life Sci 2006; 78: 2937–43.
Levy S . Dihydroxyacetone-containing sunless or self-tanning lotions. J Am Acad Dermatol 1992; 27: 989–93.
Levy S . Tanning preparations. Dermatol Clin 2000; 18: 591–6.
Fesq H, Brockow K, Strom K, Mempel M, Ring J, Abeck D . Dihydroxyacetone in a new formulation — a powerful therapeutic option in vitiligo. Dermatology 2001; 203: 241–3.
Author information
Authors and Affiliations
Corresponding author
Additional information
This work was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD) (the Center for Healthcare Technology Development, Chonbuk National University, Jeonju 561 – 756, Republic of Korea).
Rights and permissions
About this article
Cite this article
Yang, Jy., Koo, Jh., Song, Yg. et al. Stimulation of melanogenesis by scoparone in B16 melanoma cells. Acta Pharmacol Sin 27, 1467–1473 (2006). https://doi.org/10.1111/j.1745-7254.2006.00435.x
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1111/j.1745-7254.2006.00435.x
Keywords
This article is cited by
-
Pigmentation Effect of Rice Bran Extract in Hair Follicle-Like Tissue and Organ Culture Models
Tissue Engineering and Regenerative Medicine (2020)
-
Artemisia Capillaris leaves inhibit cell proliferation and induce apoptosis in hepatocellular carcinoma
BMC Complementary and Alternative Medicine (2018)
-
Influence of plasma-activated compounds on melanogenesis and tyrosinase activity
Scientific Reports (2016)
-
The effect of Rhus verniciflua Stokes (RVS) for anti-aging and whitening of skin
Oriental Pharmacy and Experimental Medicine (2014)
-
Inhibition of melanogenesis and antioxidant properties of Magnolia grandiflora L. flower extract
BMC Complementary and Alternative Medicine (2012)