α-Melanocyte-Stimulating Hormone Triggers Melanogenesis Via Activation of the Aryl Hydrocarbon Receptor Pathway in B16F10 Mouse Melanoma Cells

Bahraman, Ali Ghaffarian; Jamshidzadeh, Akram; Keshavarzi, Majid; Arabnezhad, Mohammad-Reza; Mohammadi, Hamidreza; Mohammadi-Bardbori, Afshin

doi:10.1177/1091581820987548

Cited by 10 publications

(12 citation statements)

References 29 publications

(46 reference statements)

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“…AhR activation occurs when pigmentation is induced, for example, by UV radiation or α‐MSH 32 or when some AhR ligands are present 33,34 . However, for KYN, even though it is an AhR ligand, 7 we did not see an increase in the pigmentation, quite the opposite.…”

Section: Discussioncontrasting

confidence: 61%

Kynurenine inhibits melanogenesis in human melanocyte‐keratinocyte co‐cultures and in a reconstructed 3D skin model

Branquinho

Silva

Castilho

et al. 2021

Experimental Dermatology

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Kynurenine (KYN), the most abundant metabolite of tryptophan, is classically associated with immune tolerance and tumor immune escape. In the last years, KYN is in the spotlight in other biological processes. Here, we showed that KYN inhibited tyrosinase expression and melanin content in primary human melanocyte and keratinocyte co‐cultures. Furthermore, KYN decreased melanosome content in a 3D human skin reconstruction model. In these experiments, we used tyrosine + NH4Cl to induce pigmentation. We compared the inhibitory effect of KYN on melanogenesis with the already known inhibitory effect promoted by IFN‐γ. Since increased KYN production depends on the IFN‐γ‐inducible enzyme indoleamine‐2,3‐dioxygenase (IDO), we propose that part of the effect of IFN‐γ on melanogenesis involves KYN production. From that, we tested if, during melanogenesis, changes in tryptophan metabolism would occur. For this purpose, we measured tryptophan, KYN and downstream products along with pigmentation. There were no significant changes in Trp metabolism, except for the high consumption of kynurenic acid. Our data identify the skin as a potential target for the action of KYN relevant for skin physiology and pigmentation. The results are discussed concerning the high production of KYN in skin inflammatory disorders and cancer.

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Section: Discussioncontrasting

confidence: 61%

Kynurenine inhibits melanogenesis in human melanocyte‐keratinocyte co‐cultures and in a reconstructed 3D skin model

Branquinho

Silva

Castilho

et al. 2021

Experimental Dermatology

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“…To determine the effects of SCE on inhibiting cellular melanin content production, the B16-F10 cells were first treated with the alpha-melanin stimulating hormone (α-MSH) [ 40 ]. In the normal physiology process, melanin synthesis is induced by α-MSH secreted by keratinocytes, which would then trigger melanin synthesis through binding with MC1R [ 41 , 42 ].…”

Section: Resultsmentioning

confidence: 99%

“…The grid box for the TYR receptor was positioned at the center x, y, z (22.548, 2.483, −93.071) with the size of (Å) x, y, z (40,40,40). The grid box for the MC1R receptor was positioned at the center x, y, z (92.688, 80.386, 111.935) with the size of (Å) x, y, z (44,40,40). All ligands were subjected to molecular docking with AutoDock Vina v.1.2.0 [69].…”

Section: In-silico Molecular Docking Analyses Of Bioactive Compounds ...mentioning

confidence: 99%

Brown Macroalgae Sargassum cristaefolium Extract Inhibits Melanin Production and Cellular Oxygen Stress in B16F10 Melanoma Cells

et al. 2022

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The brown macroalgae Sargassum has been reported for its anti-UV and photoprotective potential for industrial applications. This study evaluated the melanin inhibition activity of Sargassum cristaefolium (SCE) ethanol extract. Melanogenesis inhibition by SCE was assessed in vitro with B16-F10 melanoma cell models and in silico against melanin regulatory proteins Tyrosinase (TYR) and Melanocortin 1 Receptor (MC1R). The regulatory properties evaluated were the melanin content, intracellular tyrosinase activity and cellular antioxidant activities. In addition, the bioactive compounds detected in SCE were subjected to molecular docking against TYR and MC1R. Based on the results, 150 µg/mL SCE effectively inhibited the production of melanin content and intracellular tyrosinase activity. Cellular tyrosinase activity was reduced by SCE-treated cells in a concentration-dependent manner. The results were comparable to the standard tyrosinase inhibitor kojic acid. In addition, SCE effectively decreased the intracellular reactive oxygen species (ROS) levels in B16-F10 cells. The antioxidant properties may also contribute to the inhibition of melanogenesis. In addition, LCMS UHPLC-HR-ESI-MS profiling detected 33 major compounds. The results based on in silico study revealed that the bioactive compound putative kaurenoic acid showed a strong binding affinity against TYR (−6.5 kcal/mol) and MC1R (−8.6 kcal/mol). However, further molecular analyses are needed to confirm the mechanism of SCE on melanin inhibition. Nevertheless, SCE is proposed as an anti-melanogenic and antioxidant agent, which could be further developed into cosmetic skin care products.

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“…In addition to melanin metabolism, intrinsic (skin types and genetic background) and extrinsic factors (sunlight exposure levels and pollution) also influence skin color. The most important positive regulator of melanogenesis is melanocortin 1 receptor (MC1R), which is expressed on melanocytes and stimulated by keratinocyte-secreted α-melanocyte stimulating hormone (α-MSH) [ 2 ]. Activated MC1R subsequently activates cAMP response element-binding protein (CREB) and microphthalmia-associated transcription factor (MITF), a principal factor regulating melanogenesis [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

“…The most important positive regulator of melanogenesis is melanocortin 1 receptor (MC1R), which is expressed on melanocytes and stimulated by keratinocyte-secreted α-melanocyte stimulating hormone (α-MSH) [ 2 ]. Activated MC1R subsequently activates cAMP response element-binding protein (CREB) and microphthalmia-associated transcription factor (MITF), a principal factor regulating melanogenesis [ 2 ]. The MITF protein controls the transcription and translation of pigmentary tyrosinase and tyrosinase-related protein-1/-2 (TRP-1/-2) catalytic enzymes, leading to melanin production [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

The in vitro and in vivo depigmentation activity of coenzyme Q0, a major quinone derivative from Antrodia camphorata, through autophagy induction in human melanocytes and keratinocytes

Hseu,

Yeh,

Vadivalagan

et al. 2024

Cell Commun Signal

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Background Coenzyme Q0 (CoQ0), a novel quinone derivative of Antrodia camphorata, has been utilized as a therapeutic agent (including antioxidant, anti-inflammatory, antiangiogenic, antiatherosclerotic, and anticancer agents); however, its depigmenting efficiency has yet to be studied. Methods We resolved the depigmenting efficiency of CoQ0 through autophagy induction in melanoma (B16F10) and melanin-feeding keratinocyte (HaCaT) cells and in vivo Zebrafish model. Then, MPLC/HPLC analysis, MTT assay, Western blotting, immunofluorescence staining, LC3 transfection, melanin formation, GFP-LC3 puncta, AVO formation, tyrosinase activity, and TEM were used. Results CoQ0-induced autophagy in B16F10 cells was shown by enhanced LC3-II accumulation, ATG7 expression, autophagosome GFP-LC3 puncta, and AVOs formation, and ATG4B downregulation, and Beclin-1/Bcl-2 dysregulation. In α‐MSH-stimulated B16F10 cells, CoQ0 induced antimelanogenesis by suppressing CREB-MITF pathway, tyrosinase expression/activity, and melanin formation via autophagy. TEM data disclosed that CoQ0 increased melanosome-engulfing autophagosomes and autolysosomes in α‐MSH-stimulated B16F10 cells. CoQ0-inhibited melanogenesis in α‐MSH-stimulated B16F10 cells was reversed by pretreatment with the autophagy inhibitor 3-MA or silencing of LC3. Additionally, CoQ0-induced autophagy in HaCaT cells was revealed by enhanced LC3-II accumulation, autophagosome GFP-LC3 puncta and AVO formation, ATG4B downregulation, ATG5/ATG7 expression, and Beclin-1/Bcl-2 dysregulation. In melanin-feeding HaCaT cells, CoQ0 induced melanin degradation by suppressing melanosome gp100 and melanin formation via autophagy. TEM confirmed that CoQ0 increased melanosome-engulfing autophagosomes and autolysosomes in melanin-feeding HaCaT cells. Treatment with 3-MA reversed CoQ0-mediated melanin degradation in melanin-feeding HaCaT cells. In vivo study showed that CoQ0 suppressed endogenous body pigmentation by antimelanogenesis and melanin degradation through autophagy induction in a zebrafish model. Conclusions Our results showed that CoQ0 exerted antimelanogenesis and melanin degradation by inducing autophagy. CoQ0 could be used in skin-whitening formulations as a topical cosmetic application.

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α-Melanocyte-Stimulating Hormone Triggers Melanogenesis Via Activation of the Aryl Hydrocarbon Receptor Pathway in B16F10 Mouse Melanoma Cells

Cited by 10 publications

References 29 publications

Kynurenine inhibits melanogenesis in human melanocyte‐keratinocyte co‐cultures and in a reconstructed 3D skin model

Kynurenine inhibits melanogenesis in human melanocyte‐keratinocyte co‐cultures and in a reconstructed 3D skin model

Brown Macroalgae Sargassum cristaefolium Extract Inhibits Melanin Production and Cellular Oxygen Stress in B16F10 Melanoma Cells

The in vitro and in vivo depigmentation activity of coenzyme Q0, a major quinone derivative from Antrodia camphorata, through autophagy induction in human melanocytes and keratinocytes

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