title: Dual effects of acetylsalicylic acid on ERK signaling and Mitf transcription lead to inhibition of melanogenesis.
abstract: Acetylsalicylic acid (ASA) is widely used as an analgesic/antipyretic drug. It exhibits a wide range of biological effects, including preventative effects against heart attack and stroke, and the induction of apoptosis in various cancer cells. We previously found that ASA inhibits melanogenesis in B16 melanoma cells. However, the mechanisms of how ASA down-regulates melanin synthesis remain unclear. Here, we investigated the effect of ASA on melanogenic pathways, such as extracellular signal-regulated kinase (ERK) and microphthalmia-associated transcription factor (Mitf) transcription. ASA significantly inhibited melanin synthesis in a dose-dependent manner without oxidative stress and cell death. Semi-quantitative reverse transcription-polymerase chain reaction analysis showed that the inhibitory effect of ASA might be due to the inhibition of Mitf gene transcription. Interestingly, ASA also induced ERK phosphorylation. Additionally, treatment with PD98059, a specific ERK phosphorylation inhibitor, abolished the anti-melanogenic effect of ASA. These results suggest that the depigmenting effect of ASA results from down-regulation of Mitf, which is induced by both the induction of ERK phosphorylation and the inhibition of Mitf transcription.
authors.affiliation: Graduate School of Agriculture, Tamagawa University, 6-1-1 Tamagawa-gakuen, Machida, Tokyo, 194-8610, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nishio
authors.affiliation: Department of Life Science, College of Agriculture, Tamagawa University, 6-1-1 Tamagawa-gakuen, Machida, Tokyo, 194-8610, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Usami
authors.affiliation: Department of Life Science, College of Agriculture, Tamagawa University, 6-1-1 Tamagawa-gakuen, Machida, Tokyo, 194-8610, Japan.
authors.forename: Mizuki
authors.initials: M
authors.lastname: Awaji
authors.affiliation: Department of Life Science, College of Agriculture, Tamagawa University, 6-1-1 Tamagawa-gakuen, Machida, Tokyo, 194-8610, Japan.
authors.forename: Sumire
authors.initials: S
authors.lastname: Shinohara
authors.affiliation: Graduate School of Agriculture, Tamagawa University, 6-1-1 Tamagawa-gakuen, Machida, Tokyo, 194-8610, Japan. kzsato@agr.tamagawa.ac.jp.|Department of Life Science, College of Agriculture, Tamagawa University, 6-1-1 Tamagawa-gakuen, Machida, Tokyo, 194-8610, Japan. kzsato@agr.tamagawa.ac.jp.
authors.forename: Kazuomi
authors.initials: K
authors.lastname: Sato
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D008543:Melanins / Q000096:biosynthesis*; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects*; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D048049:Extracellular Signal-Regulated MAP Kinases; D001241:Aspirin
keywords: Acetylsalicylic acid (aspirin); Extracellular signal-regulated kinase (ERK); Melanin synthesis; Microphthalmia-associated transcription factor (Mitf); Non-steroidal anti-inflammatory drugs (NSAIDs)