scholarly journals Zerumbone, a Tropical Ginger Sesquiterpene of Zingiber officinale Roscoe, Attenuates α-MSH-Induced Melanogenesis in B16F10 Cells

2018 ◽  
Vol 19 (10) ◽  
pp. 3149 ◽  
Author(s):  
Taek-In Oh ◽  
Hye-Jeong Jung ◽  
Yoon-Mi Lee ◽  
Sujin Lee ◽  
Geon-Hee Kim ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Target Genes ◽  
Biological Activities ◽  
Degradation Mechanism ◽  
Zingiber Officinale ◽  
Related Protein ◽  
Active Constituent ◽  
B16f10 Cells ◽  
Extracellular Signal ◽  
Tyrosinase Related Protein

Zerumbone (ZER), an active constituent of the Zingiberaceae family, has been shown to exhibit several biological activities, such as anti-inflammatory, anti-allergic, anti-microbial, and anti-cancer; however, it has not been studied for anti-melanogenic properties. In the present study, we demonstrate that ZER and Zingiber officinale (ZO) extract significantly attenuate melanin accumulation in α-melanocyte-stimulating hormone (α-MSH)-stimulated mouse melanogenic B16F10 cells. Further, to elucidate the molecular mechanism by which ZER suppresses melanin accumulation, we analyzed the expression of melanogenesis-associated transcription factor, microphthalmia-associated transcription factor (MITF), and its target genes, such as tyrosinase, tyrosinase-related protein 1 (TYRP1), and tyrosinase-related protein 2 (TYRP2), in B16F10 cells that are stimulated by α-MSH. Here, we found that ZER inhibits the MITF-mediated expression of melanogenic genes upon α-MSH stimulation. Additionally, cells treated with different concentrations of zerumbone and ZO showed increased extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation, which are involved in the degradation mechanism of MITF. Pharmacological inhibition of ERK1/2 using U0126 sufficiently reversed the anti-melanogenic effect of ZER, suggesting that increased phosphorylation of ERK1/2 is required for its anti-melanogenic activity. Taken together, these results suggest that ZER and ZO extract can be used as active ingredients in skin-whitening cosmetics because of their anti-melanogenic effect.

scholarly journals Anti-Melanogenic Effects of Hydroxyectoine via MITF Inhibition by JNK, p38, and AKT Pathways in B16F10 Melanoma Cells

2019 ◽  
Vol 14 (6) ◽  
pp. 1934578X1985852 ◽  
Author(s):  
You C. Chung ◽  
Min-Jin Kim ◽  
Eun Y. Kang ◽  
Yun B. Kim ◽  
Bong S. Kim ◽  
...  
Keyword(s):  
Skin Color ◽  
Inhibitory Effect ◽  
Tyrosinase Activity ◽  
Dependent Manner ◽  
Related Protein ◽  
B16f10 Melanoma ◽  
Melanin Production ◽  
B16f10 Cells ◽  
Dose Dependent ◽  
Tyrosinase Related Protein

Melanin plays a role in determining human skin color of a person, and a large amount of melanin makes the skin color look darkened. The proper amount of melanin formation protects our skin from UV radiation, but excessive melanin production causes hyperpigmentation and leads to freckles, melasma, and lentigo. In this study, we investigated the inhibitory effect of hydroxyectoine on melanogenesis and its mechanism in B16F10 cells. Melanin content and cellular tyrosinase activity were determined. The expression of microphthalmia-associated transcription factor (MITF), and the activities of tyrosinase and other melanogenesis-related enzymes, such as tyrosinase-related protein 1 (TRP-1) and tyrosinase-related protein 2, were also examined. Hydroxyectoine treatment significantly inhibited melanin production and intracellular tyrosinase activity in a dose-dependent manner. Western blot analysis showed that hydroxyectoine also reduced the expressions of tyrosinase and TRP-1. In addition, hydroxyectoine significantly reduced the expression of MITF, a major regulator of melanin production, and inhibited the phosphorylation of p38, c-Jun N-terminal kinase, and activated the protein kinase B. The results demonstrated that hydroxyectoine inhibits the expression of MITF through the inhibition or activation of melanin-related signaling pathways and downregulates melanogenesis by inhibiting melanogenic enzyme expression and tyrosinase activity. Hydroxyectoine has potential value in functional cosmetics applications, such as whitening.

scholarly journals TGF-β regulates the expression of transcription factor KLF6 and its splice variants and promotes co-operative transactivation of common target genes through a Smad3–Sp1–KLF6 interaction

2009 ◽  
Vol 419 (2) ◽  
pp. 485-495 ◽  
Author(s):  
Luisa M. Botella ◽  
Francisco Sanz-Rodriguez ◽  
Yusuke Komi ◽  
Africa Fernandez-L ◽  
Elisa Varela ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Splice Variants ◽  
Biological Activities ◽  
Resonance Energy ◽  
Transforming Growth Factor Β1 ◽  
Full Length ◽  
Specific Cell ◽  
Tgf Β1

KLF6 (Krüppel-like factor 6) is a transcription factor and tumour suppressor with a growing range of biological activities and transcriptional targets. Among these, KLF6 suppresses growth through transactivation of TGF-β1 (transforming growth factor-β1). KLF6 can be alternatively spliced, generating lower-molecular-mass isoforms that antagonize the full-length WT (wild-type) protein and promote growth. A key target gene of full-length KLF6 is endoglin, which is induced in vascular injury. Endoglin, a homodimeric cell membrane glycoprotein and TGF-β auxiliary receptor, has a pro-angiogenic role in endothelial cells and is also involved in malignant progression. The aim of the present work was to explore the effect of TGF-β on KLF6 expression and splicing, and to define the contribution of TGF-β on promoters regulated by co-operation between KLF6 and Sp1 (specificity protein 1). Using co-transfection, co-immunoprecipitation and fluorescence resonance energy transfer, our data demonstrate that KLF6 co-operates with Sp1 in transcriptionally regulating KLF6-responsive genes and that this co-operation is further enhanced by TGF-β1 through at least two mechanisms. First, in specific cell types, TGF-β1 may decrease KLF6 alternative splicing, resulting in a net increase in full-length, growth-suppressive KLF6 activity. Secondly, KLF6–Sp1 co-operation is further enhanced by the TGF-β–Smad (similar to mothers against decapentaplegic) pathway via the likely formation of a tripartite KLF6–Sp1–Smad3 complex in which KLF6 interacts indirectly with Smad3 through Sp1, which may serve as a bridging molecule to co-ordinate this interaction. These findings unveil a finely tuned network of interactions between KLF6, Sp1 and TGF-β to regulate target genes.

scholarly journals Grape Extract Promoted α-MSH-Induced Melanogenesis in B16F10 Melanoma Cells, Which Was Inverse to Resveratrol

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5959
Author(s):  
Siqi Zhou ◽  
Drira Riadh ◽  
Kazuichi Sakamoto
Keyword(s):  
Biological Activities ◽  
Melanoma Cells ◽  
Positive Control ◽  
Point Of View ◽  
Melanin Synthesis ◽  
Related Protein ◽  
B16f10 Melanoma ◽  
Grape Extract ◽  
B16f10 Melanoma Cells ◽  
Tyrosinase Related Protein

Melanin is a natural pigment produced by cells to prevent damage caused by ultraviolet radiation. Previously, resveratrol was shown to reduce melanin synthesis. As a natural polyphenol with various biological activities, resveratrol occurs in a variety of beverages and plant foods, such as grapes. Therefore, we investigated whether grape extracts containing resveratrol also had the ability to regulate melanin synthesis. In this study, we used mouse B16F10 melanoma cells as a model for melanin synthesis with the melanogenesis-inducing α-melanocyte-stimulating hormone (α-MSH) as a positive control. Our results confirmed previous reports that resveratrol reduces melanin synthesis by reducing the activity of the rate-limiting enzyme tyrosinase. In contrast, the grape extract could not reduce melanin synthesis, and in fact promoted melanogenesis in the presence of α-MSH. The expression of genes related to melanin synthesis, such as tyrosinase, tyrosinase-related protein-1, tyrosinase-related protein-2, and microphthalmia-associated transcription factor, also supports these phenomena, which means that even in the presence of resveratrol, grape extract will strengthen the function of α-MSH in promoting melanin synthesis. Therefore, these results also provide a point of view for research on cosmetics.

scholarly journals 7,3′,4′-Trihydroxyisoflavone, a Metabolite of the Soy Isoflavone Daidzein, Suppresses α-Melanocyte-Stimulating Hormone-Induced Melanogenesis by Targeting Melanocortin 1 Receptor

2020 ◽  
Vol 7 ◽  
Author(s):  
Ji Hye Kim ◽  
Jae-Eun Lee ◽  
Taewon Kim ◽  
Myung Hun Yeom ◽  
Jun Seong Park ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Intracellular Camp ◽  
Related Protein ◽  
Melanin Production ◽  
Melanocortin 1 Receptor ◽  
Creb Phosphorylation ◽  
Melanocyte Stimulating Hormone ◽  
B16f10 Cells ◽  
Tyrosinase Related Protein ◽  
Stimulating Hormone

7,3′,4′-Trihydroxyisoflavone (7,3′,4′-THIF) is a metabolite of daidzein which is a representative isoflavone found in soybean. Recent studies suggested that 7,3′,4′-THIF exerts a hypopigmentary effect in B16F10 cells, however, its underlying molecular mechanisms and specific target protein remain unknown. Here, we found that 7,3′,4′-THIF, but not daidzein, inhibited α-melanocyte-stimulating hormone (MSH)-induced intracellular and extracellular melanin production in B16F10 cells by directly targeting melanocortin 1 receptor (MC1R). Western blot data showed that 7,3′,4′-THIF inhibited α-MSH-induced tyrosinase, tyrosinase-related protein-1 (TYRP-1), and tyrosinase-related protein-2 (TYRP-2) expressions through the inhibition of Microphthalmia-associated transcription factor (MITF) expression and cAMP response element-binding (CREB) phosphorylation. 7,3′,4′-THIF also inhibited α-MSH-induced dephosphorylation of AKT and phosphorylation of p38 and cAMP-dependent protein kinase (PKA). cAMP and Pull-down assays indicated that 7,3′,4′-THIF strongly inhibited forskolin-induced intracellular cAMP production and bound MC1R directly by competing with α-MSH. Moreover, 7,3′,4′-THIF inhibited α-MSH-induced intracellular melanin production in human epidermal melanocytes (HEMs). Collectively, these results demonstrate that 7,3′,4′-THIF targets MC1R, resulting in the suppression of melanin production, suggesting a protective role for 7,3′,4′-THIF against melanogenesis.

scholarly journals GIF-2209, an Oxindole Derivative, Accelerates Melanogenesis and Melanosome Secretion via the Modification of Lysosomes in B16F10 Mouse Melanoma Cells

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 177
Author(s):  
Miyu Watanabe ◽  
Kyoka Kawaguchi ◽  
Yusuke Nakamura ◽  
Kyoji Furuta ◽  
Hiroshi Takemori
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Mrna Levels ◽  
Related Protein ◽  
Mouse Melanoma ◽  
Protein Levels ◽  
Independent Mechanism ◽  
Microphthalmia Transcription Factor ◽  
Tyr Gene ◽  
Tyrosinase Related Protein

Melanogenesis and melanosome secretion are regulated by several mechanisms. In this study, we found that the oxindole derivative GIF-2209 accelerated melanogenesis associated with the discrimination in the expression and intracellular distributions of two melanogenic enzymes, tyrosinase (TYR) and tyrosinase-related protein-1 (TYRP-1). GIF-2209 upregulated the expression of TYR via a microphthalmia transcription factor (MITF)-independent mechanism, leading to high expression of protein. In contrast, GIF-2209 did not alter the mRNA levels of TYRP-1 and suppressed its protein levels. GIF-2209 induced the dissociation of TYR from TYRP-1 but did not alter the association between TYR and CD63, a melanosome and lysosome marker. The protein levels of CD63 were also upregulated by GIF-2209. GIF-2209 induced lysosome expansion and redistribution in all areas of the cytosol, accompanied by autophagy acceleration (upregulation of LC3BII protein levels and downregulation of p62 protein levels). In addition, GIF-2209 stimulated the secretion of melanosomes containing high levels of TYR, TYRP-1, and CD63 proteins. The GIF-2209 mediated melanosome secretion was sensitive to the lysosome inhibitor chloroquine. These results suggest that GIF-2209 may activate lysosomal functions with TYR gene expression, while it accelerates melanosome secretion, which finally leads to the depletion of intracellular melanogenic enzyme, especially TYRP-1 protein.

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

Antibiotics ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 172
Author(s):  
Sana Ullah ◽  
You Chul Chung ◽  
Chang-Gu Hyun
Keyword(s):  
Western Blotting ◽  
Disodium Salt ◽  
Water Soluble ◽  
Dependent Manner ◽  
Related Protein ◽  
Melanin Content ◽  
B16f10 Cells ◽  
Tract Infections ◽  
Dose Dependent ◽  
Tyrosinase Related Protein

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.

scholarly journals Phoenix dactylifera L. Seed Extract Exhibits Antioxidant Effects and Attenuates Melanogenesis in B16F10 Murine Melanoma Cells by Downregulating PKA Signaling

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1270
Author(s):  
Huey-Chun Huang ◽  
Shr-Shiuan Wang ◽  
Tsang-Chi Tsai ◽  
Wang-Ping Ko ◽  
Tsong-Min Chang
Keyword(s):  
Phoenix Dactylifera ◽  
Seed Extract ◽  
Skin Care ◽  
Tyrosinase Activity ◽  
Total Phenolic ◽  
Related Protein ◽  
Ros Scavenging ◽  
B16f10 Cells ◽  
Antioxidant Characteristics ◽  
Tyrosinase Related Protein

Background: The mode of action of Phoenix dactylifera seed extract in skin care has never been explored. Methods: P. dactylifera L. seeds were extracted by ultrasonic extraction. The antioxidant characteristics of the extract were determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-di-(3-ethylbenzthiazoline sulfonic acid) (ABTS+) assays and scavenging methods. The total phenolic content, reducing capacity, iron (II) ion-chelation, and intracellular reactive oxygen species (ROS)-scavenging capacities were also investigated. The effects of P. dactylifera L. seed extract on melanogenesis were evaluated spectrophotometrically by a mushroom tyrosinase activity assay, determination of intracellular tyrosinase activity, and melanin content. The expression levels of melanogenesis-related proteins were analyzed by Western blotting. Results: The results revealed that the P. dactylifera L. seed extract exerted apparent antioxidant capacity and significantly decreased intracellular ROS content at concentrations of 0.245 and 0.49 (mg/mL). Furthermore, the extract decreased the expression of melanocortin 1 receptor (MC1R), microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 (TRP1), and tyrosinase-related protein-2 (TRP2), and inhibited melanogenesis in B16F10 cells. Conclusions: Our results revealed that P. dactylifera L. seed extract attenuated melanogenesis in B16F10 cells by downregulating protein kinase A (PKA) signaling pathways. Hence, the extract could be used as a type of skin-whitening agent in skin care products.

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