Downregulation of melanogenesis: drug discovery and therapeutic options

Pillaiyar, Thanigaimalai; Manickam, Manoj; Jung, Sang‐Hun

doi:10.1016/j.drudis.2016.09.016

Cited by 132 publications

(124 citation statements)

References 133 publications

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“…Currently these drugs are used only topically for the treatment of hyper-pigmentation disorders). However, they block pigmentation at different levels [77] and there might be some that are compatible with systemic administration. In addition, our findings warrant studies examining whether the efficacy of BRAFi/MEKi on melanotic melanoma patients is further increased when not only pigmentation inhibitors, but also inhibitors of oxidative phosphorylation/mitochondrial biogenesis are added to the treatment regimen.…”

Section: Discussionmentioning

confidence: 99%

Context-dependent miR-204 and miR-211 affect the biological properties of amelanotic and melanotic melanoma cells

et al. 2017

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Despite increasing amounts of experimental evidence depicting the involvement of non-coding RNAs in cancer, the study of BRAFV600E-regulated genes has thus far focused mainly on protein-coding ones. Here, we identify and study the microRNAs that BRAFV600E regulates through the ERK pathway.By performing small RNA sequencing on A375 melanoma cells and a vemurafenib-resistant clone that was taken as negative control, we discover miR-204 and miR-211 as the miRNAs most induced by vemurafenib. We also demonstrate that, although belonging to the same family, these two miRNAs have distinctive features. miR-204 is under the control of STAT3 and its expression is induced in amelanotic melanoma cells, where it acts as an effector of vemurafenib's anti-motility activity by targeting AP1S2. Conversely, miR-211, a known transcriptional target of MITF, is induced in melanotic melanoma cells, where it targets EDEM1 and consequently impairs the degradation of TYROSINASE (TYR) through the ER-associated degradation (ERAD) pathway. In doing so, miR-211 serves as an effector of vemurafenib's pro-pigmentation activity. We also show that such an increase in pigmentation in turn represents an adaptive response that needs to be overcome using appropriate inhibitors in order to increase the efficacy of vemurafenib.In summary, we unveil the distinct and context-dependent activities exerted by miR-204 family members in melanoma cells. Our work challenges the widely accepted “same miRNA family = same function” rule and provides a rationale for a novel treatment strategy for melanotic melanomas that is based on the combination of ERK pathway inhibitors with pigmentation inhibitors.

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Section: Discussionmentioning

confidence: 99%

Context-dependent miR-204 and miR-211 affect the biological properties of amelanotic and melanotic melanoma cells

et al. 2017

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“…One can distinguish true tyrosinase inhibitors that reversibly bind to the enzyme, from tyrosinase inactivators, e.g., compounds forming covalent bonds with the enzyme, thus leading to its irreversible inactivation [11]. Hence, tyrosinase inhibition (by tyrosinase blockers) is still the most common strategy adopted to achieve skin whitening, but agents acting upstream or downstream also exist [53,[69][70][71]:…”

Section: Multidirectional Approaches To Modulating Skin Pigmentationmentioning

confidence: 99%

“…Melanogenesis is a complex pathway ( Figure 1) regulated by several enzymes including tyrosinase, phenylalanine hydroxylase (PHA), and tyrosinase-related proteins (TRP-1 and TRP-2) [53]. Tyrosinase, a glycosylated copper-containing polyphenol oxidase, is the key enzyme involved in the melanogenesis pathway.…”

Section: Mechanismmentioning

confidence: 99%

“…All these procedures have their own advantages and disadvantages, and may sometimes lead to false positives and false negatives: [14,53]). …”

Section: Testing the Whitening Potential Of A Given Substancementioning

confidence: 99%

“…This compound is further oxidized into dopachrome, the precursor of dihydroindole (DHI) and dihydroindole-2-carboxylic acid (DHICA), which leads through a series of oxidation reactions to the synthesis of UV-protective and ROS-scavenger eumelanins, which are brown or black pigments [11,[60][61][62]. The melanogenesis pathway (adapted from [14,53]). …”

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confidence: 99%

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Skin Whitening Cosmetics: Feedback and Challenges in the Development of Natural Skin Lighteners

et al. 2016

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Abstract:With the public's growing interest in skin whitening, lightening ingredients only used under dermatological supervision until recently, are more and more frequently incorporated into cosmetic formulas. The active agents that lighten skin tone are either natural or synthetic substances, and may act at various levels of melanogenesis. They are used to treat various skin pigmentation disorders or simply to obtain a lighter skin tone as whiter skin may be synonymous of wealth, health, youth, and/or beauty in different cultures. However, recent studies demonstrated the adverse effects of some of these ingredients, leading to their interdiction or restricted use under the European Directive and several other international regulations. After an overview of skin whitening practices and the associated risks, this article provides insight into the mechanisms involved in melanin synthesis and the biological assays available to attest the lightening activity of individual ingredients. The legislation dealing with the use of skin lighteners is then discussed. As traditional depigmenting agents such as hydroquinone and corticosteroids are of safety concern, the potential of natural extracts has been investigated more and more; finally, a synthesis of three years of research in our laboratory for such plant extracts will be given.

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Plant‐Derived Vesicle‐Like Nanoparticles as Promising Biotherapeutic Tools: Present and Future

et al. 2023

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At present, it is generally acknowledged that EVs are secreted by almost all living cells including plant cells. [4] Compared with mammalian EVs, the research of plant EVs is still in its infancy. Increasing evidence has proved that plant cells are able to secret exosome-like vesicles or extracellular vesicles into apoplast space. [5] In the 1960s, using transmission electron microscopy (TEM), Halperin et al. for the first time observed and discovered multivesicular bodies (MVBs) fusing with the plasma membrane and releasing exosome-like vesicles into the cell wall area in carrot cell cultures. [6] Fifty years after this first discovery, Regenteet al. used a tissue-infiltration-centrifugation method and successfully separated exosome-like vesicles from apoplast washing fluids (AWF) of sunflower seeds. [5a] Following these discoveries, plant exosomelike vesicles or vesicle-like nanoparticles have been successfully isolated from many plant species, including ginseng, ginger, broccoli, bitter melon, oat, grape, grapefruit, lemon, blueberry, orange, sunflower seed, and Arabidopsis, etc. [5a,7] The efficient separation of PDVLNs from plant cells is still one of the challenges that need to be solved in the plant EV field. At present, two plant tissue pre-processing methods, namely tissue-disruption and tissue-infiltration centrifugation, have emerged as favorite methods used for vesicle separation from plant cells in the field. [5b,8] After tissue pre-treatment, most studies use ultracentrifugation or density gradient centrifugation for further PDVLN separation. [5a,9] In addition, novel separation methods are under development for PDVLNs, such as ultrafiltration, immunoaffinity capture, size-exclusive chromatography, etc. [5b,7j,10] However, it is still challenging to isolate specific PDVLN subtypes, due to the lack of generic or specific markers for PDVLNs and well-verified plant species antibodies. [4b,5b] The nomenclature of vesicles prepared by these methods is not standardized in existing references. Many terms were used, including "plant particles", "plant vesicles", etc. [7b,8b,10,11] To facilitate communication in the plant vesicle field, standardizing the nomenclatures is necessary. We thus propose to unify these nomenclatures into plant-derived vesicle-like nanoparticles (PDVLNs) in this review.PDVLNs share many similar physical characteristics to those of human-derived EVs, including features such as morphology, particle size, concentration, Zeta potential, etc. [2a,7b,e,11] To further elucidate the specific molecular mechanism of PDVLNs on Extracellular vesicles (EVs) are heterogeneous, phospholipid bilayer-enclosed biological particles that regulate cell communication by molecular cargo delivery and surface signaling. EVs are secreted by almost all living cells, including plant cells. Plant-derived vesicle-like nanoparticles (PDVLNs) is a generic term referring to vesicle-like nanostructure particles isolated from plants. Their low immunogenicity and wide availability make PDVLNs safer and mor...

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Downregulation of melanogenesis: drug discovery and therapeutic options

Cited by 132 publications

References 133 publications

Context-dependent miR-204 and miR-211 affect the biological properties of amelanotic and melanotic melanoma cells

Context-dependent miR-204 and miR-211 affect the biological properties of amelanotic and melanotic melanoma cells

Skin Whitening Cosmetics: Feedback and Challenges in the Development of Natural Skin Lighteners

Plant‐Derived Vesicle‐Like Nanoparticles as Promising Biotherapeutic Tools: Present and Future

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