• Nuclear Medicine and Molecular Imaging
• /
• v.42 no.4
• /
• pp.307-313
• /
• 2008

Purpose: Vascular endothelial growth factor (VEGF) and its receptor, fetal liver kinase 1 (Flk-1), play an important role in vascular permeability and tumor angiogenesis. The aim of this study is to evaluate the therapeutic efficacy of $^{131}I$ labeled anti-Flk-1 monoclonal antibody (DC101) on the growth of melanoma tumor, which is known to be very aggressive in vivo. Materials and Methods: Balb/c nude mice were injected subcutaneously with melanoma cells in the right flank. Tumors were allowed to grow up to $200-250\;mm^3$ in volume. Gamma camera imaging and biodistribution studies were performed to identify an uptake of $^{131}I$-DC101 in various organs. Mice with tumor were randomly divided into five groups (10 mice per group) and injected intravenously; control PBS (group 1), $^{131}I$-DC101 $50\;{\mu}g/mouse$ (group 2), non-labeled DC101 $50\;{\mu}g/mouse$ (group 3), $^{131}I$-DC101 $30\;{\mu}g/mouse$ (group 4) and $15\;{\mu}g/mouse$ (group 5) every 3 or 4 days for 20 days. Tumor volume was measured with caliper twice a week. Results: In gamma camera images, the uptake of $^{131}I$-DC101 into tumor and thyroid was increased with time. Biodistribution results showed that the radioactivity of blood and other major organ was gradually decreased with time whereas tumor uptake was increased up to 48 hr and then decreased. After 4th injection of $^{131}I$-DC101, tumor volume of group 2 and 4 was significantly smaller than that group 1. After 5th injection, the tumor volume of group 5 also significantly reduced. Conclusion: These results indicated that delivery of $^{131}I$ to tumor using FlK-1 antibody, DC101, effectively blocks tumor growth in aggressive melanoma xenograft model.

• Journal of Life Science
• /
• v.31 no.8
• /
• pp.719-728
• /
• 2021

Melanin pigments are abundantly distributed in mammalian skin, hair, eyes, and nervous system. Under normal physiological conditions, melanin protects the skin against various environmental stresses and acts as a physiological redox buffer to maintain homeostasis. However, abnormal melanin accumulation results in various hyperpigmentation conditions, such as chloasma, freckles, senile lentigo, and inflammatory pigmentation. Tyrosinase, a copper-containing enzyme, plays an important role in the regulation of the melanin pigment biosynthetic pathway. Although several whitening agents based on tyrosinase inhibition have been developed, their side effects, such as allergies, DNA damage, mutagenesis, and cytotoxicity of melanocytes, limit their applications. In this study, we synthesized 4-chromanone derivatives (MHY compounds) and investigated their ability to inhibit tyrosinase activity. Of these compounds, (E)-3-(4-hydroxybenzylidene)chroman-4-one (MHY1294) more potently inhibited the enzymatic activity of tyrosinase (IC₅₀ = 5.1±0.86 μM) than kojic acid (14.3±1.43 μM), a representative tyrosinase inhibitor. In addition, MHY1294 showed competitive inhibitory action at the catalytic site of tyrosinase and had greater binding affinity at this site than kojic acid. Furthermore, MHY1294 effectively inhibited α-melanocyte stimulating hormone (α-MSH)-induced melanin synthesis and intracellular tyrosinase activity in B16F10 melanoma cells. The results of the present study indicate that MHY1294 may be considered as a candidate pharmacological agent and cosmetic whitening ingredient.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.44 no.12
• /
• pp.1905-1911
• /
• 2015

Melanin is one of the most important factors affecting skin color. Melanogenesis is the bioprocess of melanin production by melanocytes in the skin and hair follicles and is mediated by several enzymes, such as tyrosinase, tyrosinase related protein (TRP)-1, and TRP-2. Convenient enzymatic transformation of the simple phenol pyrogallol with polyphenol oxidase originating from pear to an oxidative product, purpurogallin, was efficient. The structure of the pyrogallol oxidation product was identified on the basis of spectroscopic methods. The biotransformation product purpurogallin showed significant inhibitory effects against both melanin synthesis and tyrosinase activity in a dose-dependent manner in B16 melanoma cells. In addition, purpurogallin significantly attenuated melanin production by inhibiting TRP-1, and TRP-2 expression through modulation of their corresponding transcription factors, and microphthalamia- associated transcription factor in B16 cells. Consequently, purpurogallin derived from convenient enzymatic transformation of pyrogallol might be a beneficial material for reducing skin hyperpigmentation.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
• /
• v.30 no.4
• /
• pp.49-61
• /
• 2017

Objectives : In order to find out the whitening effects of Leonuri Herba, this study was designed to identify the effects and the action mechanism of LHE(Leonuri Herba extract) on Malignant melanoma cell lines. Methods : After treating LHE on the B16F10 cell-Malignant melanoma cell line-, the cell survival rate, melanin biosynthesis rate, intra&extracellular tyrosinase activity rate, SOD-like activity, tyrosinase mRNA gene expression were investigated. The results were compared with control group without LHE treatment or with positive control group treated with whitening efficacy substance. Results : B16F10 cell survival rate, melanin biosynthesis rate, and intra&extracellular tyrosinase activity were significantly inhibited depending on the concentration of treated LHE. Melanin biosynthesis rate and tyrosinase activity rate were also decreased when ${\alpha}-MSH$ was combined with LHE. In addition, the SOD-like activity was increased in a concentration-dependent manner in the treatment with the LHE, indicating signigicant activity at high concentrations, and the tyrosinase mRNA gene expression was decreased in both the LHE-treated group, the LHE and ${\alpha}-MSH-treated$ group. Conclusions : LHE seems to inhibit melanin synthesis through inhibition of tyrosinase activity and inhibition of tyrosinase mRNA gene expression. It also has the effect of promoting SOD-like activity and may be used clinically as a skin whitening agent in the future.

• Nuclear Medicine and Molecular Imaging
• /
• v.41 no.1
• /
• pp.42-48
• /
• 2007

Purpose: The purpose of this study is to image metastaic lung melanoma model with optimal pre-conditions for animal handling by using $[^{18}F]FDG$ small animal PET and clinical CT. Materials and Methods: The pre-conditions for lung region tumor imaging were 16-22 h fasting and warming temperature at $30^{\circ}C$. Small animal PET image was obtained at 60 min postinjection of 7.4 MBq $[^{18}F]FDG$ and compared pattern of $[^{18}F]FDG$ uptake and glucose standard uptake value (SUVG) of lung region between Ketamine/Xylazine (Ke/Xy) and Isoflurane (Iso) anesthetized group in normal mice. Metastasis tumor mouse model to lung was established by intravenous injection of B16-F10 cells in C57BL/6 mice. In lung metastasis tumor model, $[^{18}F]FDG$ image was obtained and fused with anatomical clinical CT image. Results: Average blood glucose concentration in normal mice were $128.0{\pm}23.87$ and $86.0{\pm}21.65\;mg/dL$ in Ke/Xy group and Iso group, respectively. Ke/Xy group showed 1.5 fold higher blood glucose concentration than Iso group. Lung to Background ratio (L/B) in SUVG image was $8.6{\pm}0.48$ and $12.1{\pm}0.63$ in Ke/Xy group and Iso group, respectively. In tumor detection in lung region, $[^{18}F]FDG$ image of Iso group was better than that of Ke/Xy group, because of high L/B ratio. Metastatic tumor location in $[^{18}F]FDG$ small animal PET image was confirmed by fusion image using clinical CT. Conclusion: Tumor imaging in small animal lung region with $[^{18}F]FDG$ small animal PET should be considered pre-conditions which fasting, warming and an anesthesia during $[^{18}F]FDG$ uptake. Fused imaging with small animal PET and CT image could be useful for the detection of metastatic tumor in lung region.

• Journal of Life Science
• /
• v.21 no.2
• /
• pp.279-285
• /
• 2011

The objective of the present study was to evaluate the skin whitening effect of the extracts of 3 herbs, Ligularia fischeri, Solidago virga-aurea and Aruncus dioicus, which were collected from Ullung island. Tyrosinase inhibition activities were 33% in pre-fermented extracts and 45% in post-fermented ones. When tyrosinase activities in B16F10 murine melanoma cells were tested, activities in pre- and post-fermented extracts were 41 and 56.5%, respectively. Thus, the post-fermented extracts might have greater skin whitening effects. The protein expression of MITF, TRP-1, TRP-2, and tyrosinase, which are all skin-whitening related transcription factors, showed that both pre- and post-fermented herbs inhibited protein biosynthesis in B16F10 melanoma cells. Post-fermented herb extracts especially showed a greater decrease of protein expressions. The expression of MITF, a regulatory transcription factor, was also decreased by both extracts but was greater in the post-fermented ones. From the results, it can be concluded that the 3 herb extracts from Ullung island may inhibit melanin biosynthesis by the suppression of MITF activity in a signaling pathway. Results indicate that the post-fermented herbs tested in the present study had skin whitening activities and can be used as functional ingredients for food and cosmetic compositions.

• Journal of Life Science
• /
• v.22 no.7
• /
• pp.889-896
• /
• 2012

Melanin synthesis is catalyzed by tyrosinase. To investigate the whitening effect of Hizikia fusiformis, fractions from ethanol extract of H. fusiformis were prepared by a systematic fractionation procedure with solvents such as methanol, hexane, butanol, and $H_2O$. The ethanol extract and its fractions were then subjected to evaluate the inhibitory effects on the tyrosinase activity and melanin synthesis in murine B16F10 melanoma cells. The ethanol extract and aqueous fraction exhibited a whitening effect with no cytotoxicity. The ethanol extract showed the highest whitening effect among the samples. The inhibitory effect of $100{\mu}g/ml$ of ethanol extract was higher than that of $10{\mu}g/ml$ of arbutin, but it was lower than that of $10{\mu}g/ml$ of kojic acid. Furthermore, the inhibitory effects of $100{\mu}g/ml$ of methanol, hexane, butanol, and aqueous fractions were similar to those of $10{\mu}g/ml$ of arbutin. The antioxidant activities were examined by comparing the results with that of ascorbic acid as a positive control. The ethanol extract and aqueous fraction showed relatively higher DPPH radical-scavenging activities compared with the other samples. Furthermore, $500{\mu}g/ml$ of ethanol extract and aqueous fraction diminished LPS-induced iNOS expression to 82 and 80%, respectively. These results suggest that ethanol extract and aqueous fraction of H. fusiformis could be used as cosmetic ingredients for whitening and skin protection effects.

• Journal of Life Science
• /
• v.20 no.5
• /
• pp.736-744
• /
• 2010

The root of Playtcodon grandiflorum, called Platycodi radix, has been a favorite edible plant in Asia and contains a large amount of saponins. Melanoma cells (B16F10) were used to investigate the inhibitory effect of aged black Platycodi radix extract (ABPRE) on oxidative stress and matrix metalloproteinases (MMPs). Platycodon radix has been known to have a variety of medicinal effects such as prevention of gastric ulcers, antiallergenic activities, histamine release inhibition, and antioxidant effects. However, the mechanism of its action remains unclear in humans. ABPRE was prepared using ethanol extraction of aged black Platycodi radix. In an antioxidant effect study of ABPRE, it was observed that ABPRE specifically exhibited the scavenging activity of DPPH radical, but did not inhibit the production of malondialdehyde from lipid peroxidation. DNA oxidation was also blocked in the presence of ABPRE. In addition, ABPRE decreased the expression and activation of MMP-2 stimulated by phenazine methosulfate. Furthermore, ABPRE revealed the inhibitory effect on melanin production induced by L-dopa via antioxidant effect and the reduction of tyrosinase expression. Especially, the expression of antioxidant enzymes such as SOD-1 and SOD-2 regulated by Nrf2 was increased in the presence of ABPRE. Therefore, it appears that ABPRE may be a possible chemopreventive agent for the prevention of metastasis related to oxidative stress.

• Journal of the Korean Applied Science and Technology
• /
• v.32 no.2
• /
• pp.260-274
• /
• 2015

This paper has shown the experimental results about the physiological activities of water-, ethanol-, ethyl acetate-soluble fractions from ethanolic extracts of leaves, stems and roots of Cudrania tricuspidata on the skin, which has been used for a long time as a traditional herb medicine in Korea and China. The effects of these fractions on the secretion of nitric oxide and cytokines from macrophage(RAW 264.7 cell) exhibited that the ethyl acetate and water fractions from leaves inhibited the release of nitric oxide, all fractions inhibited thoses of inflammatory cytokine $IL-1{\alpha}$, and the ethyl acetate fractions of leaves, stems and roots inhibited thoses of inflammatory cytokine IL-6. The only ethylacetate fraction of leaves demonstrated significantly the reduction of melanin synthesis in melanoma cells. In order to evaluate the efficacy of collagen synthesis, the treatment with extracts on the human normal fibroblast cell(CCD-986sk cell) resulted in finding that the water fractions of leaves, stems and roots and the ethanol fractions of leaves and stems showed the increased synthesis of collagen.