• KSBB Journal
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• 제19권2호
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• pp.118-124
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• 2004

본 연구에서는 효모에서 분리한 melanoston이라고 명명된 멜라닌 생성을 억제하는 물질의 작용 기전을 밝히기 위한 것이다. $\alpha$-MSH를 처리한 B16 melanoma 세포에서 melanoston은 tyrosinase mRNA 발현양을 10% 정도 저해되는데 그쳤으며 western blotting을 이용한 단백질 측정에서도 이와 비슷한 정도의 단백질 생성 억제를 보였다. 그러나 B16 세포 배양액에 melanoston을 첨가할 경우 세포내 tyrosinase 활성이 33% 까지 감소되는 것으로 나타나 metanoston이 tyrosinase inhibitor는 아니지만 세포내 tyrosinase 활성화 (activation) 과정을 억제하는 것으로 추측할 수 있었다. 또한 광학 현미경을 이용한 morphology 관찰에서 $\alpha$-MSH를 처리한 세포에서는 많은 dentrite가 형성되면서 세포분화가 일어나는 반면 melanoston를 처리한 경우에는 dendrite가 감소하면서 세포형태가 대조군과 비슷하게 회복 되는 것을 알 수 있었다. 또 FITC-anti-tyrosinase-Ab를 이용한 형광 염색을 통해서는 $\alpha$-MSH만 처리한 세포에서는 tyrosinase의 분포가 dendrite를 포함한 세포 전체로 퍼져나가는 것을 관찰할 수 있었고 $\alpha$-MSH와 melanoston을 동시에 처리한 세포에서는 대조군과 비슷하게 tyrosinase가 핵 주변에서만 관찰되어 melanoston이 B16 melanoma 세포의 분화과정에서 이를 억제하는 효과를 주고 있음을 알 수 있었다. 이상의 결과들을 종합해 볼 때 melanoston은 $\alpha$-MSH에 진행되는 B16 세포의 분화를 억제하고 이 과정에서 멜라닌 생성의 주된 효소인 tyrosinase의 활성화를 억제하며 결과적으로는 멜라닌 생성을 저해하는 것으로 사료된다.

• 생명과학회지
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• 제23권12호
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• pp.1516-1524
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• 2013

본 연구는 Monascus purpureus (Mp), Aspergillus oryzae (Ao), Aspergillus kawachii (Ak) 및 Rhizopus oryzae (Ro) 균주로 Cordycepin-고함유 동충하초(Cordyceps militaris)(CM${\alpha}$)를 발효시켜 수용성 추출물을 얻어 페놀화합물 및 플라보노이드 농도와 항산화 및 티로시나제 저해 활성을 측정한 결과 Ak로 발효시킨 CM${\alpha}$ (AkF-CM${\alpha}$)에서 각각 46 mg/g 및 093 mg/g과 6274% 및 7997%로 가장 우수한 효과를 나타내었다. 이러한 결과로부터 AkF-CM${\alpha}$를 선택하여 멜라닌 세포(B16F0 mouse melanoma cell)에서 미백효과를 검토하였다. 양성 대조구 arbutin 처리 B16F10 melanoma 세포는 92% 이상의 세포 생육과 43%의 멜라닌 생성 억제 효능을 보였고, AkF-CM${\alpha}$ 1, 3 및 5 mg/ml 처리 시 멜라닌 생성은 각각 35, 45 및 53% 억제되었다. 또한 AkF-CM${\alpha}$은 멜라닌 세포 내 tyrosinase 활성과 mushroom tyrosinase 활성 모두를 저해시켰고, 멜라닌 생성 관련 tyrosinase 단백질 발현량도 무첨가군에 비해 처리 농도 의존적으로 억제되었다. 이상의 결과에 따라 Aspergillus kawachii 균주로 발효시킨 Cordycepin-고함유 동충하초(Cordyceps militaris)의 수용성 추출물은 미백 화장품 소재로 개발 가능성이 높은 것으로 사료된다.

• 대한한방소아과학회지
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• 제14권1호
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• pp.39-78
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• 2000

Introduction: In order to investigate the effects of partial Cervus elaphus Linne' extract on antitumoral immunological, a group of mice are melanoma-induced and observed reponses in terms of the number of lymphocyte, CD4+ count, CD8+ count, CD4+/CD8+ ratio in blood and spleen, change in body weight, melanoma weight, spleen index, NK cell activity and productivity of IL-2 in each mouse Methodology: Male C57BL/6 mice were chosen as an experimental object and were divided into 5 groups randomly selection. The normal group did not receive any induction. The control group was treated with normal saline in melanoma-induced' mice. Sample I group induced the upper part of Cervus elaphus Linne' extract in melanoma-induced mice. Sample II group was induced the middle part of Cervus elaphus Linne' extract in melanoma-induced mice. Sample III group was induced the lower part of Cervus elaphus Linne' extract in melanoma-induced mice. The dosage of medication was 0.2cc daily for 14days. Results: 1. There was a significant difference in the number of lymphocyte in spleen in the sample I (upper part of Cervus elaphus Linne' extract induced) and the sample II (middle part of Cervus elaphus Linne' extract induced) compared to the control group and the sample III (lower part of Cervus elaphus Linne' extract induced). On the other hand, no significant difference was observed in the number of lymphocyte in blood in the control group and all sample groups. 2. In the CD4+ T cell ratio in blood, all three sample groups showed differences compared to the control group, though there was no significant difference between sample groups. In the CD4+ T cell ratio in spleen, there was a difference between the sample I and the control group, while the sample II and the sample III had significant difference to the control group. And also, it has been observed there were differences between the sample I and the other samples. 3. In the CD8+ T cell ratio in spleen, all three sample groups showed significant differences compared to the control group, while there was no difference between groups in the ratio in blood. 4. In the CD4+/CD8+ T cell ratio in blood, the sample I showed a significant difference compared to the control group, while the sample 1I and sample III showed differences compared to the control group. In the CD4+/CD8+ T cell ratio in spleen, all three samples showed a significant difference compared to the control group, when the sample I had a difference to the other sample groups. 5. The spleen index of the sample I and the sample II showed a significant difference compared to the sample III and the control group. In comparison between the sample groups, the sample I and the sample II showed a significant difference to the sample III. 6. In terms of the change in body weight and melanoma weight, all three sample groups showed a significant difference compared to the control group, while the comparison between the sample groups showed the sample and the sample II had a significant difference to the sample Ⅲ. 7. In comparison of NK cell activity, the sample I had a difference compared to the other groups when the effector to target cell ratio was 2.5:1. With the ratio of 5:1, the sample I and sample II showed significant differences compared to the control group, while the sample Ⅲ showed a difference. When the effector to target cell ratio was 10:1, there was no difference between groups. 8. In the productivity of IL-2, all three sample groups showed significant differences compared to the control group. In comparison between sample groups, there were significant differences between each sample groups in order of the sample I , the sample II and the sample Ⅲ. Conclusion: As one can witness from the above results, administration of partial Cervus elaphus Linne extract played important role in antitumoral immune response in melanoma-induced mice, and it could be suggested that sample I and sample II groups have prominent antitumoral immune effect.

• BMB Reports
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• 제45권11호
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• pp.659-664
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• 2012

Extracellular superoxide dismutase (EC-SOD) overexpression modulates cellular responses such as tumor cell suppression and is induced by $IFN{\gamma}$. Therefore, we examined the role of EC-SOD in $IFN{\gamma}$-mediated tumor cell suppression. We observed that the dominant-negative protein kinase C delta ($PKC{\delta}$) suppresses $IFN{\gamma}$-induced EC-SOD expression in both keratinocytes and melanoma cells. Our results also showed that $PKC{\delta}$-induced EC-SOD expression was reduced by pretreatment with a PKC-specific inhibitor or a siRNA against $PKC{\delta}$. $PKC{\delta}$-induced EC-SOD expression suppressed cell proliferations by the up-regulation of p21 and Rb, and the downregulation of cyclin A and D. Finally, we demonstrated that increased expression of EC-SOD drastically suppressed lung melanoma proliferation in an EC-SOD transgenic mouse via p21 expression. In summary, our findings suggest that $IFN{\gamma}$-induced EC-SOD expression occurs via activation of $PKC{\delta}$. Therefore, the upregulation of EC-SOD may be effective for prevention of various cancers, including melanoma, via cell cycle arrest.

• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1551-1556
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• 2014

Background: Transient receptor potential melastatin 8 (TRPM8), a principle membrane receptor involved in calcium ion influx and cell signal transduction, has been found to be up-regulated in some cancer types, including melanomas. Efficiency of menthol, an agonist of TRPM8, in killing melanoma cancer cells has been reported previously, but the mechanisms remain unclear. We here determined whether in vitro cytotoxic effects of menthol on A-375 human malignant melanoma cells might be related to TRPM8 transcript expression. Materials and Methods: The $PrestoBlue^{(R)}$ cell viability assay was used to assess the in vitro cytotoxic effect of menthol after 24h of treatment. RT-PCR was used to quantify TRPM8 transcript expression levels in normal and menthol-treated cells. Cell morphology was observed under inverted phase contrast light microscopy. Results: TRPM8 transcript expression was found at low levels in A-375 cells and down-regulated in a potentially dose-dependent manner by menthol. Menthol exerted in vitro cytotoxic effects on A-375 cells with an $IC_{50}$ value of 11.8 ${\mu}M$, which was at least as effective as 5-fluorouracil ($IC_{50}=120{\mu}M$), a commonly applied chemotherapeutic drug. Menthol showed no dose-dependent cytotoxicity on HeLa cells, a TRPM8 non-expressing cell line. Conclusions: The cytotoxic effects on A-375 cells caused by menthol might be related to reduction of the TRPM8 transcript level. This suggests that menthol might activate TRPM8 to increase cytosolic $Ca^{2+}$ levels, which leads to cytosolic $Ca^{2+}$ imbalance and triggers cell death.

• 약학회지
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• 제47권1호
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• pp.25-30
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• 2003

This study is performed to investigate the effects of citrus essential oils on melanin production in B16 melanoma cells. Five kinds of citrus essential oils (Bergamot, Grapefruit, Lemon, Mandarin, Petigrain) did not have any influence on DPPH radical scavenger activity, cell growth and cytotoxicity in B16 melanoma cells. Both mandarin and petigrain essential oils dose-dependently inhibited purified tyrosinase activity, but bergamot did not. In 1$\mu$M MSH-stimulated B16 melanoma cells, all of 5 citrus essential oils inhibited melanin production in a dose dependent manner. From the above results, it is possible that citrus essential oils may be developed to be an anti-melanogenesis agent on the basis of their inhibitory effect on MSH-induced melanin production.

• 대한두개안면성형외과학회지
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• 제20권1호
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• pp.58-61
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• 2019

Chronic burn scars often cause various skin malignancies at rates of up to 2%. These lesions are usually squamous cell carcinomas, but rarely, malignant melanoma is reported. We report a 67-year-old male with a malignant melanoma on a burn scar with regional metastasis. This patient presented an ulcerative lesion only in 2 weeks. After histopathological diagnosis, we performed only palliative surgery on patient's demand, and followed up the subsequent deterioration course. Our case reemphasizes the need for rapid diagnosis and treatment when suspect lesions are present on chronic burn scar. Also, physician should be in mind and inform the patient about malignant melanoma and its aggressive course.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.211.1-211.1
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• 2003

There are now increasing evidences that free radicals and reactive oxygen species are involved in a variety of pathological events. Flavonoids. a group of polypenolic compounds, are widespread in the human food supply. This study was carried out to investigate the antioxidant activity of these compounds. myriceitn and (+)-catechin on B 16Fl0. murine melanoma cell line in oxidative stress. Oxidative stress was induced by exposure to hydrogen peroxide. (omitted)

• International Journal of Oral Biology
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• 제42권3호
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• pp.107-115
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• 2017

Human malignant melanoma is an aggressive skin cancer which has been rising at a greater rate than any other cancers. Although various new therapeutic methods have been developed in previous studies, this disease has properties of high proliferation and metastasis rate which remain obstacles that have lead to a poor prognosis in patients. It has been reported that a specific Lactobacillus extract has anti-cancer and -metastasis effect in vitro and in vivo. However, previous research has not specified precisely what effect the Lactobacillus rhamnosus GG (LGG) extract has had on human malignant melanomas. In this study, we showed that the LGG extract has anti-cancer and -metastasis effects on the human malignant melanoma cell lines, A375P and A375SM. At first, it was found that, while the LGG extract affects human neonatal dermal fibroblasts slightly, it induced the dose-dependent anti-cancer effect on A375P and A375SM by a WST-1 proliferation assay. As a result of a real-time PCR analysis, the expression patterns of several genes related to cell cycle, proliferation, and apoptosis were modulating in a manner that inhibited the growth of both malignant melanoma cell lines after the treatment of the LGG extract. Furthermore, genes related to the epithelial-mesenchymal transition were down-regulated, and migration rates were also decreased significantly by the LGG extract. Our study showed that the LGG extract could be used as a potential therapeutic source.

• Journal of Microbiology and Biotechnology
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• 제25권12호
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• pp.1997-2006
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• 2015

Ginsenoside Rg3 is a bioactive ginseng constituent that has been reported to have diverse pathological and physiological effects, including anti-inflammatory and anti-metastatic activities. Metastasis is one of the most important factors involved in patients with melanoma. However, the molecular mechanism underlying the anti-metastatic activities of Rg3 in malignant melanoma cancer has not been fully elucidated. In this study, we have evaluated that Rg3 effectively inhibits metastasis of B16F10 melanoma cancer cells. We found that Rg3 significantly suppresses the migration, invasion, wound healing, and colony-forming abilities of B16F10 cells in a dose-dependent manner. Mechanistically, we demonstrate that Rg3 suppresses B16F10 cell metastasis by inhibiting MMP-13 expression. These results indicate that Rg3 suppresses the metastasis of B16F10 mouse melanoma cancer cells via MMP-13 regulation. Importantly, MMP-13 downregulation may influence the migration and invasion capabilities of melanoma cells and has been correlated with melanoma progression. Therefore, Rg3 is a potential therapeutic candidate that could be used to treat patients with metastatic melanoma.