Effect of heterocyclic pyrimidine compounds on UVB-induced cell damage in human keratinocytes and on melanogenesis in mouse B16 cells.
We investigated the protective effect of several heterocyclic pyrimidine compounds against ultraviolet B (UVB)-induced damage in human keratinocyte HaCaT cells, as well as the inhibitory effect on melanogenesis in B16 melanoma cells. One of the compounds examined, 2-piperadino-6-methyl-5-oxo-5,6-dihydro(7H)pyrrolo[3,4d]pyrimidine maleate (MS-818), showed low cytotoxicity even at 500 microM. At 50-500 microM, MS-818 dose-dependently suppressed the UVB (100 mJ/cm(2))-induced elevation of tumor necrosis factor alpha (TNF-alpha), one of the trigger cytokines for cell death, in HaCaT cells. In addition, MS-818 (100 microM) markedly inhibited melanogenesis in B16 melanoma cells via downregulation of tyrosinase expression mediated by microphthalmia-associated transcription factor (MITF) and extracellular signal-regulated kinase (ERK). In conclusion, MS-818 protected epidermal cells from UVB-induced damage and also suppressed melanogenesis in melanoma cells. It appears to be a good candidate for a new UVB-protective and whitening agent for application in cosmetics.
Shimoda
Nao
N
Faculty of Pharmaceutical Sciences, Tokyo University of Science (TUS), 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
Mutou
Yasuko
Y
Shimura
Noriko
N
Tsukimoto
Mitsutoshi
M
Awaya
Akira
A
Kojima
Shuji
S
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D008543:Melanins / Q000096:biosynthesis*; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use; D011837:Radiation-Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*
D000970:Antineoplastic Agents; D006571:Heterocyclic Compounds; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D011743:Pyrimidines; D011837:Radiation-Protective Agents; D014409:Tumor Necrosis Factor-alpha; D014442:Monophenol Monooxygenase; D048049:Extracellular Signal-Regulated MAP Kinases