Induction of Melanogenesis by Fosfomycin in B16F10 Cells Through the Upregulation of P-JNK and P-p38 Signaling Pathways

Abstract

Fosfomycin disodium salt (FDS), which is a water-soluble extract, is a bactericidal drug used to inhibit the synthesis of cells. Moreover, it has been found to be effective in the treatment of urinary tract infections. The present study was conducted to investigate the melanogenesis-stimulating effect of FDS in B16F10 cells. Several experiments were performed on B16F10 cells: the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, the melanin content assay, the cellular tyrosinase activity assay, and Western blotting. FDS upregulated the activity of tyrosinase in a dose-dependent manner at a wide concentration range of 0–1 mg/mL, which showed no cytotoxicity. It also increased the melanin content and the activity of the microphthalmia-associated transcription factor (MITF), tyrosinase related protein 1 (TRP-1), and tyrosinase related protein 2 (TRP-2) enzymes in a dose-dependent manner. Western blotting results showed that FDS clearly upregulated the phosphorylation of c-Jun N-terminal kinases (JNK) and p38 pathways. These data are clear evidence of the melanogenesis-inducing effect of FDS in B16F10 murine melanoma cells.

Tuliposides H–J and Bioactive Components from the Bulb of Amana edulis

“…Consequently, individual 4 , 6 , 10 , and 12 did not increase melanin productions alone ( Figure S27 ) similar to those shown in Figure 4 , and it was suggested the abovementioned four compounds could merely enhance melanogenesis effects of α-MSH. Accordingly, additional signal pathways in melanogenesis, such as tyrosinase-related protein-1 (TRP-1), TRP-2, microphthalmia-associated transcription factor, melanocortin 1 receptor, cyclic adenosine monophosphate, protein kinase A, cAMP-response element-binding protein, c-Jun N-terminal kinases, extracellular signal-regulated kinase, p38, and phosphoinositide 3-kinase/protein kinase B [ 7 , 21 ], should be further tested and confirmed for those active components.…”

“…When exposed to the ultraviolet radiation of solar light or harmful chemicals and pathogenic factors, moderate melanogenesis can protect our skin from reactive oxygen species generation in keratinocytes and melanocytes [ 6 ]. Tyrosinase is an important enzyme in melanogenesis to produce more melanin for us to defense against aforementioned hazardous conditions [ 7 ]. Therefore, the active components of A. edulis are worthy to be clarified for further medical applications.…”

Lincomycin induces melanogenesis through the activation of MITF via p38 MAPK, AKT, and PKA signaling pathways

“…For several years, our research team has studied the pathways involved in regulating pigmentation by treating melanocytes with specific substances or old antibiotics. It has also been suggested that these compounds or old antibiotics may be used as therapeutic or cosmetic agents [27,28].…”

“…Therefore, we performed an experiment focusing on new efficacy of lincomycin. Recent studies have reported that several antibiotics isolated from Streptomyces species, such as tobramycin, fosfomycin (melanogenesis stimulator), and kanamycin (melanogenesis inhibitor), are related to melanogenesis [26][27][28]. However, the effect of lincomycin on melanogenesis has not yet been investigated.…”

Cajanin Suppresses Melanin Synthesis through Modulating MITF in Human Melanin-Producing Cells

“…Meanwhile, Dct catalyzes the conversion of dopachrome into 5,6-dihydroxyindole-2-carboxylic acid (DHICA) which is subsequently changed to brown-black melanin (Eumelanin) by TRP-1 [ 7 ]. Thus, both up-regulated expression level and activated enzymatic function of tyrosinase family proteins dramatically increase melanin production in melanocytes [ 8 , 9 ]. As a key enzyme accelerating the first and rate-limiting step in melanin biosynthesis, the inhibition of tyrosinase is highlighted as a potential mode to treat hyperpigmentation.…”