Anti-melanogenic activity of phytosphingosine via the modulation of the microphthalmia-associated transcription factor signaling pathway

Jang, Eun Jeong; Shin, Yeong Gil; Park, Hyen Joo; Kim, Donghwa; Jung, Cholomi; Hong, Ji‐Young; Kim, Sanghee; Lee, Sang Kook

doi:10.1016/j.jdermsci.2017.03.011

Cited by 26 publications

(17 citation statements)

References 43 publications

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“…We propose two plausible hypothesis. First, NAT10 may act as a transcriptional activator of MITF promoter alone or in cooperation with several transcription factors, including cAMP response element-binding protein (CREB), paired box 3 (PAX3), SRY-related HMG-box 10 (SOX10), and lymphoid enhancing factor-1 (LEF-1), which are known as upstream transcription regulators of MITF [ 17 ]. Alternatively, NAT10 may regulate post-translational modification such as N -terminal acetylation of MITF or its upstream transcription regulators.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of NAT10 Suppresses Melanogenesis and Melanoma Growth by Attenuating Microphthalmia-Associated Transcription Factor (MITF) Expression

Lee

Lim

et al. 2017

IJMS

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N-acetyltransferase 10 (NAT10) has been considered a target for the treatment of human diseases such as cancer and laminopathies; however, its functional role in the biology of melanocytes is questionable. Using a small molecule or small interfering RNA targeting NAT10, we examined the effect of NAT10 inhibition on melanogenesis and melanoma growth in human and mouse melanoma cells. Genetic silencing or chemical inhibition of NAT10 resulted in diminished melanin synthesis through the suppression of melanogenesis-stimulating genes such as those encoding dopachrome tautomerase (DCT) and tyrosinase in B16F10 melanoma cells. In addition, NAT10 inhibition significantly increased cell cycle arrest in S-phase, thereby suppressing the growth and proliferation of malignant melanoma cells in vitro and in vivo. These results demonstrate the potential role of NAT10 in melanogenesis and melanoma growth through the regulation of microphthalmia-associated transcription factor (MITF) expression and provide a promising strategy for the treatment of various skin diseases (melanoma) and pigmentation disorders (chloasma and freckles).

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Section: Discussionmentioning

confidence: 99%

Inhibition of NAT10 Suppresses Melanogenesis and Melanoma Growth by Attenuating Microphthalmia-Associated Transcription Factor (MITF) Expression

Lee

Lim

et al. 2017

IJMS

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“…It is responsible for the regulation of key genes for melanocyte development and differentiation [48]. It was found that the suppression of the MITF gene expression and degradation of the MITF protein or negatively regulation of its stability inhibited melanin synthesis [49,50].…”

Section: Discussionmentioning

confidence: 99%

Molecular and Biochemical Basis of Minocycline-Induced Hyperpigmentation—The Study on Normal Human Melanocytes Exposed to UVA and UVB Radiation

Rok

Rzepka

Kowalska

et al. 2021

IJMS

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Minocycline is a drug which induces skin hyperpigmentation. Its frequency reaches up to 50% of treated patients. The adverse effect diminishes the great therapeutic potential of minocycline, including antibacterial, neuroprotective, anti-inflammatory and anti-cancer actions. It is supposed that an elevated melanin level and drug accumulation in melanin-containing cells are related to skin hyperpigmentation. This study aimed to evaluate molecular and biochemical mechanism of minocycline-induced hyperpigmentation in human normal melanocytes, as well as the contribution of UV radiation to this side effect. The experiments involved the evaluation of cyto- and phototoxic potential of the drug using cell imaging with light and confocal microscopes as well as biochemical and molecular analysis of melanogenesis. We showed that minocycline induced melanin synthesis in epidermal melanocytes. The action was intensified by UV irradiation, especially with the UVB spectrum. Minocycline stimulated the expression of microphthalmia-associated transcription factor (MITF) and tyrosinase (TYR) gene. Higher levels of melanin and increased activity of tyrosinase were also observed in treated cells. Moreover, minocycline triggered the supranuclear accumulation of tyrosinase, similar to UV radiation. The decreased level of premelanosome protein PMEL17 observed in all minocycline-treated cultures suggests disorder of the formation, maturation or distribution of melanosomes. The study revealed that minocycline itself was able to enhance melanin synthesis. The action was intensified by irradiation, especially with the UVB spectrum. Demonstrated results confirmed the potential role of melanin and UV radiation minocycline-induced skin hyperpigmentation.

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“…When the levels of TRP-1 and TRP-2 were increased by up-regulated expression of MITF, the expression of tyrosinase was promoted and the melanogenesis-related enzymes produced melanin [18,32]. The expression of melanogenesis-mediated proteins was observed using western blotting to determine the anti-melanogenic effect of EU extract and fractions in B16-F10 melanoma cells.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Effect of Elaeagnus umbellata Fractions on Melanogenesis in α-MSH-Stimulated B16-F10 Melanoma Cells

Lee

Jeon

et al. 2021

Molecules

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When skin is exposed to UV radiation, melanocytes produce melanin. Excessive melanin production leads to skin pigmentation, which causes various cosmetic and health problems. Therefore, the development of safe, natural therapeutics that inhibit the production of melanin is necessary. Elaeagnus umbellata (EU) has long been widely used as a folk medicinal plant because of pharmacological properties that include anti-ulcer, antioxidant, and anti-inflammatory properties. In this study, we investigated the antioxidant activity and melanogenesis inhibitory effects of EU fractions in B16-F10 melanoma cells. EU fractions showed a dose-dependent increase in antioxidant activity in radical scavenging activity. In addition, we evaluated the effect of EU fractions on tyrosinase activity and melanogenesis in α-melanocyte-stimulating hormone-induced B16-F10 melanoma cells. EU was noncytotoxic at 12.5–50 μg/mL. EU fractions effectively inhibited tyrosinase activity and melanogenesis, suppressed the phosphorylation of CREB and ERK involved in the melanogenesis pathway, and down-regulated expression of melanogenesis-related proteins. Interestingly, the anti-melanogenesis effect was most effective at a concentration of 50 μg/mL EU, and the effects of the fractions were superior to those of the extract. Therefore, our study suggests that EU has potential as a safe treatment for excessive pigmentation or as a natural ingredient in cosmetics.

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Anti-melanogenic activity of phytosphingosine via the modulation of the microphthalmia-associated transcription factor signaling pathway

Cited by 26 publications

References 43 publications

Inhibition of NAT10 Suppresses Melanogenesis and Melanoma Growth by Attenuating Microphthalmia-Associated Transcription Factor (MITF) Expression

Inhibition of NAT10 Suppresses Melanogenesis and Melanoma Growth by Attenuating Microphthalmia-Associated Transcription Factor (MITF) Expression

Molecular and Biochemical Basis of Minocycline-Induced Hyperpigmentation—The Study on Normal Human Melanocytes Exposed to UVA and UVB Radiation

Inhibitory Effect of Elaeagnus umbellata Fractions on Melanogenesis in α-MSH-Stimulated B16-F10 Melanoma Cells

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