• Journal of Life Science
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• v.24 no.4
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• pp.454-460
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• 2014

In a previous study, we found that methanolic extracts of immature fruits of Satuma mandarin (Citrus unshiu Marc. var. okitsu) contained relatively high amounts of phytochemicals. Here we show that a combined treatment consisting of immature fruits of Satuma mandarin and cisplatin induced strong apoptotic response in human melanoma A375 cells. We further investigated the mechanisms by which immature fruits of Satuma mandarin augment cisplatin-induced apoptosis in A375 cells. Satuma mandarin up-regulated the expression of nitric oxide synthase (NOS), elevated nitric oxide ($NO^{\cdot}$) production, and weakening the anti-apoptotic signals inhibitor of apoptosis (IAP) family, thus facilitating the process of apoptosis. These results suggest that immature fruits of Satuma mandarin in combination with cisplatin might have therapeutic value in melanoma treatment worthy of further development.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.166.1-166.1
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• 2003

Autotaxin (ATX) is a 125-kDa glycoprotein and a strong motogen that can increase invasiveness and angiogenesis, originally isolated from the conditioned medium of human melanoma A2058 cells. And it is a strong. Recently, we suggested that ATX promotes motility via G protein-coupled PI3K$\gamma$, and Cdc42/Racl are essential for ATX-induced tumor cell motility in A2058 melanoma cells. In the present study, we found that activation of p21-activated kinase1 (PAK1) was required for ATX-induced cell motility. (omitted)

• Journal of the Society of Cosmetic Scientists of Korea
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• v.30 no.1
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• pp.33-38
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• 2004

Melanin pigmentation in human skin is a major defense mechanism against ultraviolet light of the sun, but abnormal pigmentation such as freckles, liver spot could be a serious aesthetic problem. Nearly all studies are mainly concentrated on searching for the materials that have inhibitory activities on tyrosinase. In this work, to isolate phenolic compounds from Gastrodia elata, we purified the extract through solvent fractionation, column chromatography, and recrystallization. They were identified as 4-hydroxybenzyl alcohol 1, bis(4-hydroxyphenyl)methane 2, gastrodin (4-${\beta}$-D-glucopyranosyloxybenzyl alcohol) 3 on the base of spectroscopic evidences. In order to investigate their depigmentation effect, inhibitory activity against mushroom tyrosinase and inhibitory activity of melanin synthesis in B16 melanoma cells were evaluated in vitro. We have found that 4-hydroxybenzyl alcohol 1 and gastrodin (4- ${\beta}$-D-glucopyranosyloxybenzyl alcohol) 3 have no tyrosinase inhibitory activity, but inhibit the melanin synthesis in B16 melanoma cells. Tyrosinase inhibitory activities of bis(4-hydroxyphenyl)methane 2 (IC$\_$50/ = 400 $\mu\textrm{g}$/mL) and butanol fraction (IC$\_$50/ = 46 $\mu\textrm{g}$/mL) were lower/higher than that of arbutin (IC$\_$50/ = 114 $\mu\textrm{g}$/mL), but inhibitory activities of melanin synthesis in B16 melanoma cells were much higher than that of arbutin. Especially, tyrosinase inhibitory activities of isolated phenolic fraction (IC$\_$50/ = 2.37 $\mu\textrm{g}$/mL) from butanol fraction was very higher than that of arbutin (IC$\_$50/ = 114 $\mu\textrm{g}$/mL). Therefore, these results suggest that isolated phenolic compounds from Gastrodia elata have inhibitory activity against mushroom tyrosinase and inhibitory activity of melanin synthesis in 816 melanoma cells in vitro.

• Herbal Formula Science
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• v.10 no.2
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• pp.199-211
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• 2002

Acquired pigmentary skin diseases such as abnormal melanogenesis, vitiligo, chloasma and inflammatory pigmentation are related to regulate the melanin production. The aim of this study was to investigate the effect of Codonopsis lanceolata on the melanogenesis of HM3KO human melanoma cells biologically. The cells were treated for 5 days with Codonopsis lanceolata at several concentrations. Treatment with Codonopsis lanceolata suppressed melanin contents as a dose dependent manner without cytotoxicity and morphological change. And the extract of Codonopsis lanceolata also inhibited tyrosinase, a key enzyme forming melanin, in a dose-dependent manner. And it did not affect the DOPAchrome tautomerase(TRP-2) activity. These results suggest that Codonopsis lanceolata is a candidate for an efficient whitening agent which supresses melanogenesis by a Raper-Mason pathway.

• Korean Journal of Korean Medical Institute of Dermatology and Aesthetics
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• v.1 no.1
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• pp.41-52
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• 2005

The aim of this study was to investigate the effect of Fructus Forsythiae on the melanogenesis. To determine whether Fructus Forsythiae methanol extract suppress melanin synthesis in cellular level, HM3KO human melanoma cells were cultured in the presence of various concentrations of Fructus Forsythiae methanol extract and the effects on cell proliferation, tyrosinase activity and melanin contents were examined. Treatment with Fructus Forsythiae methanol extract inhibited tyrosinase activity, regulate melanin biosynthesis as the key enzyme in melanogenesis, in a dose-dependent manner. And also suppressed melanin contents as a dose dependent manner without cytotoxicity morphological change. It was observed that the color of cell pellets was totally different from the control. These results suggest that the inhibitory effect of Fructus Forsythiae methanol extract on melanogenesis is due to the suppression of tyrosinase in HM3KO cells and Fructus Forsythiae is a candidate for an efficient whitening agent.

• BMB Reports
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• v.51 no.11
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• pp.572-577
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• 2018

Recent studies showed that the PD-1/PD-L1 checkpoint blockade is a dramatic therapy for melanoma by enhancing antitumor immune activity. Currently, major strategies for the PD-1/PD-L1 blockade have mainly focused on the use of antibodies and compounds. Seeking an alternative approach, others employ endogenous proteins as blocking agents. The extracellular domain of PD-1 (ePD1) includes the binding site with PD-L1. Accordingly, we constructed a PD-1-based recombinantly tailored fusion protein (dFv-ePD1) that consists of bivalent variable fragments (dFv) of an MMP-2/9-targeted antibody and ePD1. The melanoma-binding intensity and antitumor activity were also investigated. We found the intense and selective binding capability of the protein dFv-ePD1 to human melanoma specimens was confirmed by a tissue microarray. In addition, dFv-ePD1 significantly suppressed the migration and invasion of mouse melanoma B16-F1 cells, and displayed cytotoxicity to cancer cells in vitro. Notably, dFv-ePD1 significantly inhibited the growth of mouse melanoma B16-F1 tumor cells in mice and in vivo fluorescence imaging showed that dFv-ePD was gradually accumulated into the B16-F1 tumor. Also the B16-F1 tumor fluorescence intensity at the tumor site was stronger than that of dFv. This study indicates that the recombinant protein dFv-ePD1 has an intensive melanoma-binding capability and exerts potent therapeutic efficacy against melanoma. The novel format of the PD-L1-blocked agent may play an active role in antitumor immunotherapy.

• Journal of Microbiology and Biotechnology
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• v.32 no.4
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• pp.531-540
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• 2022

Due to the high incidence of malignant melanoma, the establishment of in vitro models that recapitulate the tumor microenvironment is of great biological and clinical importance for tumor treatment and drug research. In this study, 3D printing technology was used to prepare GelMA/PEGDA composite scaffolds that mimic the microenvironment of human malignant melanoma cell (A375) growth and construct in vitro melanoma micro-models. The GelMA/PEGDA hybrid scaffold was tested by the mechanical property, cell live/dead assay, cell proliferation assay, cytoskeleton staining and drug loading assay. The growth of tumor cells in two- and three-dimensional culture systems and the anti-cancer effect of luteolin were evaluated using the live/dead staining method and the Cell Counting Kit-8 (CCK-8) method. The results showed a high aggregation of tumor cells on the 3D scaffold, which was suitable for long-term culture. Cytoskeleton staining and immunofluorescent protein staining were used to evaluate the degree of differentiation of tumor cells under 2D and 3D culture systems. The results indicated that 3D bioprinted scaffolds were more suitable for tumor cell expansion and differentiation, and the tumor cells were more aggressive. In addition, luteolin was time- and dose-dependent on tumor cells, and tumor cells in the 3D culture system were more resistant to the drug.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.30 no.4 s.48
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• pp.485-489
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• 2004

Melanin pigmentation in human skin is a major defensive mechanism against ultraviolet light of the sun. Tyrosinase plays a key role in the biosynthesis of melanin. This is why many researches have been focused on regulations in controlling the epidermal melanization. We found that extract of Canavalia lineata inhibits mushroom tyrosinase activity, dopa oxidase activity, and melanin synthesis in B16F10 melanoma cells. To elucidate mRNA level reverse transcription polymerase chain reaction (RT-PCR) technique was used. It was revealed that A subfraction of $CHCI_3$ extract of Canavalia lineara reduced the tyrosinase mRNA expression of B16F10 melanoma cells by reverse transcription polymerase chain reaction (RT-PCR) technique.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.22 no.2
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• pp.104-117
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• 2009

Objective : Melanin is one of the most important facor in skin color. Melanin protects human skin from ultraviolet radiation otherwise it causes melanin pigmentation. So this experiment is carried out for test whether Scutellaria baicalensis Georgi(SBG) inhibits melanin synthesis and tyrosinase activity in mouse B16 melanoma cells. Method : The melanin synthesis inhibition effects of SBG were examined by in vitro melanin production assay. We assessed inhibitory effects of SBG on melanin contents from B16F1 melanoma cell, on tyrosinase activity(cell and cell free system), effect of SBG on the expression tyrosinase, Microphthalmia-associated Transcription Factor(MITF), Extracellular signal-regulated Kinase(ERK). Result : SBG inhibited melanin synthesis induced $\alpha$-MSH($\alpha$-Melanin Stimulating Hormone) in B16F1. SBG inhibited tyrosinase activity and expression. And SBG down-regulates MITF and stimulated ERK activation in B16F1. Conclusion : According to above results, SBG was improved its suppression effect to the inhibition of melanin synthesis, tyrosinase activation, and tyrosinase promotor activation. So SBG is considered to be used for an strong source of skin whitening effect.

• Journal of Microbiology and Biotechnology
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• v.30 no.8
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• pp.1184-1194
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• 2020

Melanin is a major factor that darkens skin color as one of the defense systems to prevent the harmful effects of UV light. However, darkened skin from the localized or systemic accumulation of melanin is viewed in many cultures as an esthetic problem. Consequentially, searching for anti-melanogenic agents from natural sources is very popular worldwide. Previous screening of fermented rice products, obtained from various rice cultivars fermented with different sources of loog-pang (Thai traditional fermentation starter), revealed that the highest ability to reduce the melanin content in B16F10 melanoma cells was from unpolished black rice fermented with a defined starter mixture of microbes isolated from loog-pang E11. The aim of this study was to investigate the mechanism of the fermented unpolished black rice (FUBR) on the inhibition of melanogenesis in B16F10 melanoma cells. The strongest reduction of cellular melanin content was found in the FUBR sap (FUBRS). The melanin reduction activity was consistent with the significant decrease in the intracellular tyrosinase activity. The FUBRS showed no cytotoxic effect to B16F10 melanoma or Hs68 human fibroblast cell lines. It also significantly reduced the transcript and protein expression levels of tyrosinase, tyrosinase-related protein 1 (TYRP-1), TYRP-2, and microphthalmia-associated transcription factor. Furthermore, it induced a significantly increased level of phosphorylated ERK, p38 and Akt signaling pathways, which likely contributed to the negative regulation of melanogenesis. From these results, a model for the mechanism of FUBRS on melanogenesis inhibition was proposed. Moreover, these results strongly suggested that FUBRS possesses anti-melanogenesis activity with high potential for cosmeceutical application as a skin depigmenting agent.