Fluvastatin increases tyrosinase synthesis induced by alpha-melanocyte-stimulating hormone in B16F10 melanoma cells.
The aim of this study was to evaluate the effect of fluvastatin on the alpha-melanocyte-stimulating hormone-mediated increase in tyrosinase activity in the melanoma B16F10 cell line and to establish whether Akt and extracellular signal-regulated kinase (Erk) inhibition is involved in tyrosinase synthesis after fluvastatin administration. Fluvastatin modulates alpha-melanocyte-stimulating hormone induced melanogenesis by increasing tyrosinase mRNA production, as shown by real time PCR, or tyrosinase protein synthesis, as presented by western blot technique. The stimulatory effect of fluvastatin on melanogenesis was, in part, induced by modulation of cell proliferation (decreased melanoma cell proliferation in G2/M phase) and possibly decrease of Akt. These findings indicate that fluvastatin increases tyrosinase synthesis induced by alpha-melanocyte-stimulating hormone in B16F10 cells and reveal an unknown effect of statin use: their influence on melanin production.
Galus
Ryszard
R
Department of Histology and Embryology, Center for Biostructure, Medical University of Warsaw, Chałubińskiego 5, PL 02-004 Warszawa, Poland. rgalus@ib.amwaw.edu.pl
Niderla
Justyna
J
Sladowski
Dariusz
D
Sajjad
Emir
E
Włodarski
Krzysztof
K
Jóźwiak
Jarosław
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D000077340:Fluvastatin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008546:Melanoma, Experimental / Q000378:metabolism*; D051379:Mice; D014442:Monophenol Monooxygenase / Q000096:biosynthesis*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012334:RNA, Neoplasm / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000521:alpha-MSH / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D012334:RNA, Neoplasm; D000077340:Fluvastatin; D000521:alpha-MSH; D014442:Monophenol Monooxygenase; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases