Transport and Distribution of Melanosomes

Gele, Mireille Van; Lambert, Jo

doi:10.1002/9783527636150.ch10

Cited by 2 publications

(2 citation statements)

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“…One caveat while extrapolating results from single cell culture is that the role of the surrounding cell types is absent, which might have a regulatory effect on the results of recovery experiments. As keratinocytes and melanocytes both exist in a symbiotic manner in the epidermis [ 38 ], paracrine factors from keratinocytes that are known to regulate melanogenesis [ 39 , 40 , 41 ] might be needed to restore melanin levels to baseline. A rigorous study of such a hypothesis might help provide insights into studies of the reversibility of skin depigmenting candidates, which are worthy of further investigation.…”

Section: Discussionmentioning

confidence: 99%

Novel Hydrogenated Derivatives of Chemically Modified Curcumin CMC2.24 Are Potent Inhibitors of Melanogenesis in an In Vitro Model: Influence of Degree of Hydrogenation

Goenka

2023

Life

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Chemically modified curcumin, CMC2.24, is a promising therapeutic that has shown efficacy in ameliorating excessive pigmentation in our previous studies. However, its inherent disadvantages of color, stability, solubility, and cytotoxicity to melanocytes and keratinocytes at concentrations > 4 µg/mL posed challenges in its use in cosmetic formulations. To overcome these limitations, chemical reduction by hydrogenation of CMC2.24 (compound 1) was developed to yield products at different time points of hydrogenation (1 h, 2 h, 4 h, and 24 h) referred to as partially (2, 3, 4) or fully hydrogenated (5) products, and the effects of the degree of hydrogenation on melanogenesis in vitro were explored. Compound 1 and products 2–5 were evaluated using mushroom tyrosinase activity assays with two substrates (L-tyrosine and L-DOPA), then cellular assays using B16F10 mouse melanoma cells, MNT-1 human melanoma cells, and physiological normal human melanocytes (HEMn-DP cells). The cytotoxicity, melanin contents, cellular tyrosinase activities, and cellular oxidative stress were evaluated. Moreover, the recovery of melanin contents in HEMn-DP cells was also studied. Our results provide novel insights into the role of the degree of hydrogenation of compound 1 on the biological effects of melanogenesis, which were dependent on cell type. To the best of our knowledge, this is the first study to show that in HEMn-DP cells, the anti-melanogenic efficacy of the yellow-colored CMC2.24 is retained as early as 1 h after its hydrogenation; this efficacy is enhanced with longer durations of hydrogenation, with a robust efficacy achieved for the 24 h hydrogenated product 5 at the lowest concentration of 4 µg/mL. A similar potency could be achieved for product 4 at higher concentrations, although interestingly, both differ only by a minor amount of dihydro-CMC2.24. Our results indicate promise for using products 4 & 5 as a skin-lightener in cosmetic formulations with the advantages of lack of color combined with a potency much greater than that of the parent compound 1 at lower concentrations and reversibility of the effects on melanocytes. This, along with the easy synthesis and scale-up of the hydrogenation method for CMC2.24 and the documented higher solubility, stability, and bioavailability of tetrahydrocurcumin, provides further impetus to incorporating these derivatives in cosmetic formulations. The results of this study can help to extend the therapeutic window of the lead compound CMC2.24 by providing options for selecting partially or fully hydrogenated derivatives for cosmetic applications where a trade-off between color and efficacy is needed. Thus, the degree of hydrogenation can be tuned for desired biological effects. Further studies are warranted to evaluate the efficacy of products 4 & 5 at suppressing pigmentation in 3D skin-tissue equivalents and in vivo models.

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Section: Discussionmentioning

confidence: 99%

Novel Hydrogenated Derivatives of Chemically Modified Curcumin CMC2.24 Are Potent Inhibitors of Melanogenesis in an In Vitro Model: Influence of Degree of Hydrogenation

Goenka

2023

Life

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“…The major mechanism of pigment transfer involves the phagocytosis by epithelial cells of melanosomecontaining melanocyte dendrites (see review by Van Gele & Lambert, [25]). The transfer process involves protease activated receptor-2 (PAR-2) which is expressed on the keratocyte surface and enhances phagocytosis.…”

Section: Cytocrine Pigment Transfer and Loss Of Melanocyte Volumementioning

confidence: 99%

The Influence of Pigment Transfer on the Risk of Developing Melanoma: The Significance of the Melanocyte Amputation Cycle

Riley

2016

J. Anal. Oncol.

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It has been shown that cancer incidence is not only a function of the size of the population at risk but is strongly associated with the turnover rate of the tissue concerned. There is a strong negative correlation between melanoma incidence and the degree of skin pigmentation, and yet the melanocyte density is the same for all races. The proposal advanced in this communication is that the probability of undergoing malignant change is critically dependent on the melanocyte turnover and that this is regulated by the pigmentation process. In melanocytes, the division rate is influenced by the process of pigment donation, probably by a mechanism whereby the continual cytoplasmic loss due to cytocrine transfer of melanosomes (termed the 'Amputation Cycle') inhibits replication. Consequently the turnover of melanocyte stem cells in heavily pigmented epidermis will be diminished, and this is held to account for the strong negative correlation between the degree of skin pigmentation and melanoma incidence.

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Transport and Distribution of Melanosomes

Cited by 2 publications

References 122 publications

Novel Hydrogenated Derivatives of Chemically Modified Curcumin CMC2.24 Are Potent Inhibitors of Melanogenesis in an In Vitro Model: Influence of Degree of Hydrogenation

Novel Hydrogenated Derivatives of Chemically Modified Curcumin CMC2.24 Are Potent Inhibitors of Melanogenesis in an In Vitro Model: Influence of Degree of Hydrogenation

The Influence of Pigment Transfer on the Risk of Developing Melanoma: The Significance of the Melanocyte Amputation Cycle

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