Inhibitory effects of 2-amino-3H-phenoxazin-3-one on the melanogenesis of murine B16 melanoma cell line.
Hyperpigmentations are a serious concern addressed by both the medical community and the cosmetic industry through the development of agents that block melanin biosynthesis. In this study, we found that 2-amino-3H-phenoxazin-3-one (APO), isolated from extracts of the edible mushroom Agaricus bisporus Imbach, exhibited potent inhibitory effects on melanogenesis in B16 cells, a murine melanoma cell line. APO inhibited melanin biosynthesis at 1,000 times lower concentrations (IC(50)=1.31+/-0.08 microM) than kojic acid (IC(50)=1.31+/-0.13 mM), without causing cellular toxicity. APO did not directly inhibit the enzyme activity of tyrosinase, the rate-limiting melanogenic enzyme. Further study showed that APO inhibited the protein expression of tyrosinase and microphthalmia-associated transcription factor (MITF), a melanogenic transcription factor that regulates the expression of tyrosinase. These results suggest that APO is a promising depigmenting agent with both therapeutic and cosmetic value in preventing melanogenesis.
Miyake
Masaki
M
Biomedical Institute, Research Center, Hayashibara Biochemical Laboratories, Inc., Okayama, Japan. fujisaki@hayashibara.co.jp
Yamamoto
Shigeto
S
Sano
Osamu
O
Fujii
Mitsukiyo
M
Kohno
Keizo
K
Ushio
Shimpei
S
Iwaki
Kanso
K
Fukuda
Shigeharu
S
D000363:Agaricales / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D007211:Indoles; D008543:Melanins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism; D008546:Melanoma, Experimental / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D011753:Pyrones; D014157:Transcription Factors / Q000378:metabolism
D007211:Indoles; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D011753:Pyrones; D014157:Transcription Factors; C009904:melanogen; C011890:kojic acid; D014442:Monophenol Monooxygenase