Flumequine-Mediated Upregulation of p38 MAPK and JNK Results in Melanogenesis in B16F10 Cells and Zebrafish Larvae

Karunarathne, Wisurumuni Arachchilage Hasitha Maduranga; Molagoda, Ilandarage Menu Neelaka; Kim, Myung Sook; Choi, Yung Hyun; Oren, Matan; Park, Eui Kyun; Kim, Gi‐Young

doi:10.3390/biom9100596

Cited by 27 publications

(24 citation statements)

References 28 publications

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“…Extracellular signal-regulated protein kinase (ERK), p38, and c-jun N-terminal kinase (JNK) have essential roles in melanogenesis regulation [ 21 , 22 , 23 ]. Interfering with p38, MAPK expression has been reported to promote melanogenesis and tyrosinase expression [ 24 ], while the active form of ERK, on the other hand, phosphorylates MITF at serine-73 during the posttranslational process, leading to its ubiquitination and, subsequently, its degradation [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Elucidation of Melanogenesis-Associated Signaling Pathways Regulated by Argan Press Cake in B16 Melanoma Cells

et al. 2021

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The beneficial effect on health of argan oil is recognized worldwide. We have previously reported that the cake that remains after argan oil extraction (argan press-cake or APC) inhibits melanogenesis in B16 melanoma cells in a time-dependent manner without cytotoxicity. In this study, the global gene expression profile of B16 melanoma cells treated with APC extract was determined in order to gain an understanding of the possible mechanisms of action of APC. The results suggest that APC extract inhibits melanin biosynthesis by down-regulating microphthalmia-associated transcription factor (Mitf) and its downstream signaling pathway through JNK signaling activation, and the inhibition of Wnt/β-catenin and cAMP/PKA signaling pathways. APC extract also prevented the transport of melanosomes by down-regulating Rab27a expression. These results suggest that APC may be an important natural skin whitening product and pharmacological agent used for clinical treatment of pigmentary disorders.

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Section: Introductionmentioning

confidence: 99%

Elucidation of Melanogenesis-Associated Signaling Pathways Regulated by Argan Press Cake in B16 Melanoma Cells

et al. 2021

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“…We, in the current study, investigated the effects of anthocyanins from two H. syriacus L. varieties, Pulsae and Paektanshim (PS and PTS, respectively) which have different petal colors (Pulsae: purple; Paektanshim: white), on melanogenesis regulation in α-MSH-treated B16F10 cells and zebrafish larvae, because B16F10 cells and zebrafish larvae have been widely used for melanin formation due to its genomic correlation with human pigmentation [21,22,23]. PS and PTS significantly downregulated melanogenesis in B16F10 cells and zebrafish larvae by inhibiting the expression of MITF and tyrosinase.…”

Section: Introductionmentioning

confidence: 99%

Anthocyanins from Hibiscus syriacus L. Inhibit Melanogenesis by Activating the ERK Signaling Pathway

et al. 2019

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Hibiscus syriacus L. exhibited promising potential as a new source of food and colorants containing various anthocyanins. However, the function of anthocyanins from H. syriacus L. has not been investigated. In the current study, we evaluated whether anthocyanins from the H. syriacus L. varieties Pulsae and Paektanshim (PS and PTS) inhibit melanin biogenesis. B16F10 cells and zebrafish larvae were exposed to PS and PTS in the presence or absence of α-melanocyte-stimulating hormone (α-MSH), and melanin contents accompanied by its regulating genes and proteins were analyzed. PS and PTS moderately downregulated mushroom tyrosinase activity in vitro, but significantly decreased extracellular and intracellular melanin production in B16F10 cells, and inhibited α-MSH-induced expression of microphthalmia-associated transcription factor (MITF) and tyrosinase. PS and PTS also attenuated pigmentation in α-MSH-stimulated zebrafish larvae. Furthermore, PS and PTS activated the phosphorylation of extracellular signal-regulated kinase (ERK), whereas PD98059, a specific ERK inhibitor, completely reversed PS- and PTS-mediated anti-melanogenic activity in B16F10 cells and zebrafish larvae, which indicates that PS- and PTS-mediated anti-melanogenic activity is due to ERK activation. Moreover, chromatography data showed that PS and PTS possessed 17 identical anthocyanins as a negative regulator of ERK. These findings suggested that anthocyanins from PS and PTS inhibited melanogenesis in vitro and in vivo by activating the ERK signaling pathway.

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“…Our findings of melanosome aggregation by AP in B16F10 cells are similar to results of another study where a natural compound hesperidin induced melanosome aggregation accompanied by a reduction in melanin secretion in Melan-a cells [ 32 ]. Our studies for extracellular melanin in B16F10 cells were conducted with phenol-red-containing medium, which is routinely used for these cells; we conducted these assays based on published studies, which also used phenol-red-containing medium for extracellular assay measurements [ 33 , 34 , 35 , 36 ]. As our control group also consisted of phenol red, we believe that the interference of phenol red with absorbance values will not affect the results, which were reported as relative levels of melanin secreted as % of the control group.…”

Section: Discussionmentioning

confidence: 99%

Asoprisnil, a Selective Progesterone Receptor Modulator (SPRM), Inhibits Melanosome Export in B16F10 Cells and HEMn-DP Melanocytes

Goenka

Simon

2020

Molecules

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Previous studies have reported that estrogen hormone promotes melanogenesis while progesterone inhibits it. A selective estrogen receptor modulator (SERM), tamoxifen, has been shown to promote melanogenesis; however, to date, there have been no reports on the effects of a selective progesterone receptor modulator (SPRM) on melanogenesis. In the present study, we hypothesized that asoprisnil (AP), a SPRM, inhibits melanogenesis. AP was tested for cytotoxicity to B16F10 mouse melanoma cells for screening the nontoxic concentrations using MTS cytotoxicity assay. Extracellular and intracellular melanin levels were estimated at nontoxic concentrations of AP. To evaluate the direct effect of AP on tyrosinase enzyme, tyrosinase activity and copper chelating activities were measured. Next, the effects of AP on melanogenesis were tested in normal human melanocytes, neonatal, darkly pigmented (HEMn-DP). Our results demonstrate that AP was nontoxic at a concentration range of 10–50 μM in B16F10 cells; AP at 50 μM significantly suppressed extracellular melanin levels comparable to kojic acid at 500 μM, with no significant effect on intracellular melanin levels. The mechanism of melanogenesis inhibition was studied to assess if AP downregulated tyrosinase activity in cell lysates or in a cell-free system. However, AP was found to increase intracellular tyrosinase activity without any effect on tyrosinase enzyme activity or copper chelating activity in a cell-free system, indicating that AP inhibits melanogenesis by mechanisms other than direct effects on tyrosinase enzyme activity. The capacity of AP to inhibit melanosome export was further validated in HEMn-DP cells; AP significantly suppressed dendricity at concentrations of 20 and 30 μM in the absence of effects on melanin synthesis or intracellular tyrosinase activity. In addition, AP was nontoxic to human keratinocytes (HaCaT) at these concentrations, validating its safety for topical use. Taken together, our preliminary results demonstrate that AP might be repurposed as a candidate therapeutic for treatment of hyperpigmentation disorders via a unique mechanism, which encompasses a selective inhibition of melanosome export.

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Flumequine-Mediated Upregulation of p38 MAPK and JNK Results in Melanogenesis in B16F10 Cells and Zebrafish Larvae

Cited by 27 publications

References 28 publications

Elucidation of Melanogenesis-Associated Signaling Pathways Regulated by Argan Press Cake in B16 Melanoma Cells

Elucidation of Melanogenesis-Associated Signaling Pathways Regulated by Argan Press Cake in B16 Melanoma Cells

Anthocyanins from Hibiscus syriacus L. Inhibit Melanogenesis by Activating the ERK Signaling Pathway

Asoprisnil, a Selective Progesterone Receptor Modulator (SPRM), Inhibits Melanosome Export in B16F10 Cells and HEMn-DP Melanocytes

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