Synthesized quercetin derivatives stimulate melanogenesis in B16 melanoma cells by influencing the expression of melanin biosynthesis proteins MITF and p38 MAPK.
In order to understand the effect of structure-activity relationships on melanogenesis using B16 melanoma cells, 19 quercetin derivatives were synthesized. Among the synthesized compounds, 3-O-methylquercetin (11) and 3',4',7-O-trimethylquercetin (14) increased melanin content more potently than the positive control theophylline, while exhibiting low cytotoxicity. Compound 11 exhibited less melanogenesis-stimulating activity than compound 14. However, 11 increased the expression of tyrosinase and tyrosinase-related protein 1 (TRP-1) to a greater extent than 14, thereby suggesting that melanogenesis in melanoma cells does not depend solely on the expression of the enzymes catalyzing melanin biosynthesis. Furthermore, 14 also stimulated the expression of the microphthalmia-associated transcription factor (MITF) and p-p38 mitogen activated protein kinase (MAPK), while they were not increased by 11. These results suggest that 11 may enhance the expression of tyrosinase and TRP-1 by regulating the proteasomal degradation of melanogenic enzymes and/or by activating other transcriptional factors regulating enzyme expression.
The United Graduate School of Agricultural Science, Gifu University, 1-1 Yanagido, 501-1193 Gifu, Japan.
Kosei
K
Yamauchi
The United Graduate School of Agricultural Science, Gifu University, 1-1 Yanagido, 501-1193 Gifu, Japan. Electronic address: mitunaga@gifu-u.ac.jp.
Tohru
T
Mitsunaga
The United Graduate School of Agricultural Science, Gifu University, 1-1 Yanagido, 501-1193 Gifu, Japan.
Mizuho
M
Inagaki
The United Graduate School of Agricultural Science, Gifu University, 1-1 Yanagido, 501-1193 Gifu, Japan.
Tohru
T
Suzuki
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008543:Melanins / Q000096:biosynthesis* / Q000737:chemistry; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism*; D015394:Molecular Structure; D011794:Quercetin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D011794:Quercetin; D048051:p38 Mitogen-Activated Protein Kinases
B16 melanoma cells; Quercetin; TRP-1; Tyrosinase