16-Kauren-2-beta-18,19-triol inhibits melanosome transport in melanocytes by down-regulation of melanophilin expression

Myung, Cheol Hwan; Kim, Kyuri; Park, Jong Il; Lee, Ji Eun; Lee, Jeong-Ah; Hong, Sung Chan; Lim, Kyung Min; Hwang, Jae Sung

doi:10.1016/j.jdermsci.2019.12.009

Cited by 10 publications

(15 citation statements)

References 28 publications

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“…Our results of reduction in dendricity are similar to those reported for the compound centauridein [31]. Our observations of perinuclear aggregation of melanosomes by CMT-308 are similar to the findings in previous reports where compounds, 16-kauren-2-beta-18, 19-triol [73], 2-methyl-naphtho[1,2,3-de] quinolin-8-one [74], and wogonin [75] suppressed the export of melanosomes by inducing their perinuclear aggregation. Melanosome aggregation and melanocyte dendritogenesis have been described as arising from the opposing actions of kinesin and dynein on melanosome trafficking, but they can be uncoupled by certain interventions [76].…”

Section: Discussionsupporting

confidence: 92%

CMT-308, a Nonantimicrobial Chemically-Modified Tetracycline, Exhibits Anti-Melanogenic Activity by Suppression of Melanosome Export

Goenka

Simon

2020

Biomedicines

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CMT-308 is a nonantimicrobial chemically-modified tetracycline (CMT), which we have previously shown exhibits antifungal activity and pleiotropic anti-inflammatory activities, including inhibition of the enzymatic activity of matrix metalloproteinases (MMPs). Based on its chemical structure, we hypothesized that CMT-308 could inhibit melanogenesis and might be a candidate for the treatment of skin hyperpigmentation disorders which occur due to unregulated melanin biosynthesis and/or transport. CMT-308 was first studied for any effects on activity of the enzyme tyrosinase in vitro using a purified preparation of mushroom tyrosinase; the mode of inhibition of the soluble fungal enzyme was evaluated by Lineweaver-Burk and Dixon plots as well as by non-linear least squares fitting. Next, the effects of CMT-308 were tested in mammalian cell cultures using B16F10 mouse melanoma cells and further validated in darkly-pigmented human melanocytes (HEMn-DP). Our results showed that micromolar concentrations of CMT-308 inhibited mushroom tyrosinase enzyme activity, using the first two substrates in the melanogenesis pathway (l-tyrosine and l-3,4-dihydroxyphenylalanine (l-DOPA)); CMT-308 inhibited mushroom tyrosinase primarily via a mixed mode of inhibition, with the major contribution from a competitive mode. In B16F10 cell cultures, CMT-308 (10 µM) significantly diminished total melanin levels with a selective reduction of extracellular melanin levels, under both basal and hormone-stimulated conditions without any cytotoxicity over a duration of 72 h. Studies of potential mechanisms of inhibition of melanogenesis in B16F10 cells showed that, in mammalian cells, CMT-308 did not inhibit intracellular tyrosinase activity or the activity of α-glucosidase, an enzyme that regulates maturation of tyrosinase. However, CMT-308 suppressed MITF protein expression in B16F10 cells and showed copper chelating activity and antioxidant activity in a cell-free system. The significantly lower extracellular melanin levels obtained at 10 µM indicate that CMT-308’s anti-melanogenic action may be attributed to a selective inhibition of melanosome export with the perinuclear aggregation of melanosomes, rather than a direct effect on the tyrosinase-catalyzed steps in melanin biosynthesis. These results were validated in HEMn-DP cells where CMT-308 suppressed dendricity in a fully reversible manner without affecting intracellular melanin synthesis. Furthermore, the capacity of CMT-308 to inhibit melanosome export was retained in cocultures of HEMn-DP and HaCaT. In summary, our results offer promise for therapeutic strategies to combat the effects of hyperpigmentation by use of CMT-308 at low micromolar concentrations.

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Section: Discussionsupporting

confidence: 92%

CMT-308, a Nonantimicrobial Chemically-Modified Tetracycline, Exhibits Anti-Melanogenic Activity by Suppression of Melanosome Export

Goenka

Simon

2020

Biomedicines

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“…MITF provides central links between transcription factors and signaling pathways in melanocytes for cell survival, proliferation, and differentiation [26], suggesting that deoxyvasicinone may generally affect melanocyte activation. Indeed, deoxyvasicinone was effective in the reduction of melanosome accumulation and dendrite extension in the co-culture of MNT-1 and HaCaT cells, an in vitro system reflecting the cross-talk between melanocytes and keratinocytes [27]. When melanin is synthesized in melanocytes, melanosomes are transferred from melanocyte to keratinocyte by extension of the melanocyte dendrites, and α-MSH stimulation promotes the extension of dendrites through upregulating melanosome transporter proteins [16,28].…”

Section: Discussionmentioning

confidence: 99%

Deoxyvasicinone with Anti-Melanogenic Activity from Marine-Derived Streptomyces sp. CNQ-617

et al. 2022

Self Cite

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The tricyclic quinazoline alkaloid deoxyvasicinone (DOV, 1) was isolated from a marine-derived Streptomyces sp. CNQ-617, and its anti-melanogenic effects were investigated. Deoxyvasicinone was shown to decrease the melanin content of B16F10 and MNT-1 cells that have been stimulated by α-melanocyte-stimulating hormone (α-MSH). In addition, microscopic images of the cells showed that deoxyvasicinone attenuated melanocyte activation. Although, deoxyvasicinone did not directly inhibit tyrosinase (TYR) enzymatic activity, real-time PCR showed that it inhibited the mRNA expression of TYR, tyrosinase-related protein 1 (TRP-1), and tyrosinase-related protein 2 (TRP-2). In the artificial 3D pigmented skin model MelanodermTM, deoxyvasicinone brightened the skin significantly, as confirmed by histological examination. In conclusion, this study demonstrated that the marine microbial natural product deoxyvascinone has an anti-melanogenic effect through downregulation of melanogenic enzymes.

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“…The objects to be measured will be directly coated on the epidermal surface with barrier function. After a period of time, the changes of deep melanocytes are detected by several detection indexes, including the quantification of melanin particles, tyrosinase activity measurement, western blot analysis, specific MART-1 immunofluorescence staining, QRT-PCR and pixel analysis software to evaluate the whitening efficacy of the subjects (Hatem et al, 2022;Myung et al, 2020). Melanin skin models exert their highly similar characteristics to skin structure and function, but 3D skin model tests are expensive and cannot fully mimic the growing environment of melanocytes in vivo.…”

Section: In Vitro Experimentsmentioning

confidence: 99%

Review on oral plant extracts in Skin Whitening

WANG¹,

An²,

Qu³

et al. 2022

Food Sci. Technol

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Skin whitening has become one of the aesthetic problems among humans around the world, especially on women which is highly attention to skin beauty and whitening. Many of the plant extracts in oral energy drinks have whitening effects and good taste, which can support the health of the skin. We use the National Center for Biotechnology Information (NCBI) as a search engine to find literatures about skin whitening, oral plant extracts. This review mainly introduces the mechanism of skin whitening and the application of oral plant extracts in skin whitening. Skin whitening at melanin synthesis, melanosome transport, metabolism, oxidative stress, UV stimulation, other environmental stimulation inseparable. Many oral plant extracts are natural tyrosine inhibitors. The review concludes the melanin synthesis and transporting, pathway of melanin synthesis, whitening mechanism and the function of whitening on Green tea polyphenols, Rose Petal Extract (Rosa gallica), Pears, Peony, Rosa roxburghii Tratt, Olive (Olea europaea L.), Pomegranates, Phyllanthus emblica L., Mulberry extract, Açaí berry, saussurea involucrate flavonoids extract, etc. These will provide a strong foundation for the application of oral plant extracts in skin whitening. Furthermore, the mixture with function of skin whitening/ skin anti-aging / anti-inflammatory antioxidant oral plant extract can be a good candidate for further development on skin care product.

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16-Kauren-2-beta-18,19-triol inhibits melanosome transport in melanocytes by down-regulation of melanophilin expression

Cited by 10 publications

References 28 publications

CMT-308, a Nonantimicrobial Chemically-Modified Tetracycline, Exhibits Anti-Melanogenic Activity by Suppression of Melanosome Export

CMT-308, a Nonantimicrobial Chemically-Modified Tetracycline, Exhibits Anti-Melanogenic Activity by Suppression of Melanosome Export

Deoxyvasicinone with Anti-Melanogenic Activity from Marine-Derived Streptomyces sp. CNQ-617

Review on oral plant extracts in Skin Whitening

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