Inhibitory effect of danazol on melanogenesis in mouse B16 melanoma cells
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Abstract
In the present study, more than 200 generic drugs were screened to verify their applicability as a skin-lightening agent using mouse B16 melanoma cells. Of the numerous agents, danazol was found to inhibit melanogenesis in B16 cells in a dose-dependent manner with an IC50 value of 9.3 μM. In addition, danazol reduced cellular tyrosinase activity in B16 cells but did not directly inhibit the murine tyrosinase activity in the cell-free system. Western blotting analysis confirmed that danazol downregulated the levels of tyrosinase protein in B16 cells, and reverse-transcription polymerase chain reaction (RT-PCR) analysis revealed that danazol did not downregulate the levels of tyrosinase mRNA in the cells. These results indicate that danazol inhibits melanogenesis in B16 cells via reducing the tyrosinase activity by post-transcriptional regulation.
Key words
Danazol Melanogenesis Tyrosinase Melanin InhibitionPreview
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References
- Ando, H., Kondoh, H., Ichihashi, M., and Hearing, V. J., Approaches to identify inhibitors of melanin biosynthesis via the quality control of tyrosinase. J. Invest. Dermatol., 127, 751–761 (2007).CrossRefPubMedGoogle Scholar
- Chang, T. S., An updated review on tyrosinase inhibitors. Int. J. Mol. Sci., 10, 2440–2475 (2009).CrossRefPubMedGoogle Scholar
- Chang, T. S., Lin, M. Y., and Lin, H. J., Identifying 8-hydroxynaringenin as a suicide substrate of mushroom tyrosinase. J. Cosmet. Sci., 61, 205–210 (2010).PubMedGoogle Scholar
- Crotty, B. A., Znaiden, A. P., and Johnson, A., Method and composition for skin lightening. U.S. Patent, 5858997 (Jan. 12, 1999).Google Scholar
- Ding, H. Y., Lin, H. C., and Chang, T. S., Tyrosinase inhibitors isolated from the roots of Paeonia suffruticosa. J. Cosmet. Sci., 60, 347–352 (2009).PubMedGoogle Scholar
- Hamilton, J. B. and Hubert G., Photographic nature of tanning of the human skin as shown by studies of male hormone therapy. Science, 88, 481 (1938).CrossRefPubMedGoogle Scholar
- Igarashi, M., Iizuka, M., Abe, Y., and Ibuki, Y., Novel vaginal danazol ring therapy for pelvic endometriosis, in particular deeply infiltrating endometriosis. Hum. Reprod., 13, 1952–1956 (1998).CrossRefPubMedGoogle Scholar
- Imokawa, G., Autocrine and paracrine regulation of melanocytes in human skin and in pigmentary disorders. Pigment Cell Res., 17, 96–110 (2004).CrossRefPubMedGoogle Scholar
- Kline, E. L., Carland, K. C., Warren, J. T., and Smith, T. J., Effect of testosterone on imidazole-induced tyrosinase expression in B16 melanoma cell culture. Cancer Res., 48, 3586–3590 (1988).PubMedGoogle Scholar
- Mun, Y. J., Lee, S. W., Jeong, H. W., Lee, K. G., Kim, J. H., and Woo, W. H., Inhibitory effect of miconazole on melanogenesis. Biol. Pharm. Bull., 27, 806–809 (2004).CrossRefPubMedGoogle Scholar
- Neeley, E., Fritch, G., Fuller, A., Wolfe, J., Wright, J., and Flurkey, W., Variations in IC50 values with purity of mushroom tyrosinase. Int. J. Mol. Sci., 10, 3811–3823 (2009).CrossRefPubMedGoogle Scholar
- Sato, K., Takahashi, H., Iraha, R., and Toriyama, M., Downregulation of tyrosinase expression by acetylsalicylic acid in murine B16 melanoma. Biol. Pharm. Bull., 31, 33–37 (2008).CrossRefPubMedGoogle Scholar
- Slominski, A., Tobin, D. J., Shibahara, S., and Wortsman, J., Melanin pigmentation in mammalian skin and its hormonal regulation. Physiol. Rev., 84, 1155–1228 (2004).CrossRefPubMedGoogle Scholar
- Solano, F., Briganti, S., Picardo, M., and Ghanem, G., Hypopigmenting agents: an updated review on biological, chemical and clinical aspects. Pigment Cell Res., 19, 550–571 (2006).CrossRefPubMedGoogle Scholar
- Spencer, J. D. and Schallreuter, K. U., Regulation of pigmentation in human epidermal melanocytes by functional high-affinity β-melanocyte-stimulating hormone/melanocortin-4 receptor signaling. Endocrinology, 150, 1250–1258 (2009).CrossRefPubMedGoogle Scholar
- Tadokoro, T., Rouzaud, F., Itami, S., Hearing, V. J., and Yoshikawa, K., The inhibitory effect of androgen and sexhormone-binding globulin on the intracellular cAMP level and tyrosinase activity. Pigment Cell Res., 16, 190–197 (2003).CrossRefPubMedGoogle Scholar
- Tai, S. S., Lin, C. G., Wu, M. H., and Chang, T. S., Evaluation of depigmenting activity by 8-hydroxydaidzein in mouse B16 melanoma cells and human volunteers. Int. J. Mol. Sci., 10, 4257–4266 (2009).CrossRefPubMedGoogle Scholar
- Zhu, W. and Gao, J., The use of botanical extracts as topical skin-lightening agents for the improvement of skin pigmentation disorders. J. Investig. Dermatol. Symp. Proc., 13, 20–24 (2008).CrossRefPubMedGoogle Scholar