• The Korean Journal of Food And Nutrition
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• v.35 no.3
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• pp.178-184
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• 2022

The objective of the present study was to investigate the molecular mechanisms involved in the activity of [10]-gingerol using A2058 human melanoma cells. [10]-Gingerol inhibited the proliferation of A2058 cells by 50% at a concentration of 52 μM. Such inhibition was dose-dependent accompanied by morphological change indicative of apoptosis. Furthermore, flow cytometric analysis by Annexin V and PI double staining showed that [10]-gingerol increased the extent of apoptosis. Analysis of the mechanism of these events indicated that [10]-gingerol increased the ratio of Bax to Bcl-2, resulting in the activation of caspase-9, caspase-3, and poly-ADP-ribose polymerase in a dose-dependent manner.

• Korean Journal of Veterinary Pathology
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• v.2 no.1
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• pp.25-30
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• 1998

An in vivo model for human melanoma was established with the growth and metastasis of SK-MEL-2 cells. The tumor was introduced into C.B-17 SCID(severe combined immunodeficiency) mice intraperiotneally subcutaeously and intravenous inoculations. Tumors developed in 100% of mice inoculated subcutaneously and intraeritoneally both at site of inoculation and as metastatic tumor in the liver lungs and diaphragm. With intravenous inoculation 50% of mice showed metastasis in the spleen. Additionally metastatic foci that were not detected either by gross and/or standard histopathologic examination were demonstrated in the spleen and lungs by immunohistochemistry with HMB-45 monoclonal antibody. We conclude that the SCID mouse supports growth and metastasis of human malignant melanoma SK-MEL-2 cells.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.23 no.2
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• pp.81-108
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• 2010

Objective : Thujae Orientalis Folium (TOF) can cool the blood and stop bleeding, eliminate phlegm and relieve cough in Oriental medicine. In addition, the fresh is used alone externally. Recently, TOF is known to have anti-tumor component. And also known to have tyrosinase inhibitory effect. Method : For these reasons, this study was designed to investigate anti-cancer and whitening activities of TOF. In this experiment, effects of TOF on proliferation rates of melanoma cells and on changes in genetic profiles were investigated. The genetic profile for the effect on human derived melanoma cell, SK-MEL-2, was measured using microarray technique, and the functional analysis on these genes was conducted. Results : Total 541 genes were up-regulated and 1,079 genes down-regulated in cells treated with TOF. Genes induced by TOF were mainly concerned with anti-cancer effects and apoptosis. Genes suppresed by TOF were related in extracellular signalling pathway. The network of total protein interactions was measured using cytoscape program, and some key molecules, such as THAP1, MAX1, STAM2, SMAD6, CYCS, PEX5, PSEN1, NONO, MAP2K7 and CREB1 that can be used for elucidation of therapeutical mechanism of medicine in future were identified. Conculusion : These results suggest possibility of TOF as anti-cancer drug for human melanoma. In addition, the present author also suggest that related mechanisms are involved in inhibition of several cancer pathway, activation of apoptosis pathway and suppression of general metabolic pathway.

• IMMUNE NETWORK
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• v.15 no.2
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• pp.58-65
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• 2015

Melanoma is the most aggressive skin cancer and its incidence is gradually increasing worldwide. Patients with metastatic melanoma have a very poor prognosis (estimated 5-year survival rate of <16%). In the last few years, several drugs have been approved for malignant melanoma, such as tyrosine kinase inhibitors and immune checkpoint blockades. Although new therapeutic agents have improved progression-free and overall survival, their use is limited by drug resistance and drug-related toxicity. At the same time, adoptive cell therapy of metastatic melanoma with tumor-infiltrating lymphocytes has shown promising results in preclinical and clinical studies. In this review, we summarize the currently available drugs for treatment of malignant melanoma. In addition, we suggest cytokine-induced killer (CIK) cells as another candidate approach for adoptive cell therapy of melanoma. Our preclinical study and several previous studies have shown that CIK cells have potent anti-tumor activity against melanomas in vitro and in an in vivo human tumor xenograft model without any toxicity.

• BMB Reports
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• v.57 no.6
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• pp.299-304
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• 2024

Upregulation of PRAME (preferentially expressed antigen of melanoma) has been implicated in the progression of a variety of cancers, including melanoma. The tumor suppressor p53 is a transcriptional regulator that mediates cell cycle arrest and apoptosis in response to stress signals. Here, we report that PRAME is a novel repressive target of p53. This was supported by analysis of melanoma cell lines carrying wild-type p53 and human melanoma databases. mRNA expression of PRAME was downregulated by p53 overexpression and activation using DNA-damaging agents, but upregulated by p53 depletion. We identified a p53-responsive element (p53RE) in the promoter region of PRAME. Luciferase and ChIP assays showed that p53 represses the transcriptional activity of the PRAME promoter and is recruited to the p53RE together with HDAC1 upon etoposide treatment. The functional significance of p53 activation-mediated PRAME downregulation was demonstrated by measuring colony formation and p27 expression in melanoma cells. These data suggest that p53 activation, which leads to PRAME downregulation, could be a therapeutic strategy in melanoma cells.

• Journal of the Korean Applied Science and Technology
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• v.27 no.1
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• pp.20-28
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• 2010

Melanoma is the most aggressive form of skin cancer and is the fastest growing type of cancer in the United States. We report here the synthesis of a novel series of quinazolinylmethoxybenzene derivatives 1a-c and their antiproliferative activities against A375 human melanoma cell line. Among them, urea compound 1a ($IC_{50}\;=\;4.8\;{\mu}M$) having 4-chloro-3-trifluoromethylphenyl moiety showed superior antiproliferative activity to Sorafenib ($IC_{50}\;=\;5.5\;{\mu}M$) as a reference compound. These results will helpful for designing structure of a therapeutic agent for the treatment of melanoma.

• Journal of the Korean Applied Science and Technology
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• v.26 no.3
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• pp.297-305
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• 2009

Melanoma is the most serious type of skin cancer as a malignant tumor of melanocytes. In this work, the syntheses of a novel series of benzaminoquinoline derivatives 1a-c and their antiproliferative activities against A375 human melanoma cell line were described. All the compounds ($IC_{50}=0.78-1.02{\mu}M$) showed superior antiproliferative activities to Sorafenib ($IC_{50}=5.58{\mu}M$) as a reference compound. These results suggested that benzaminoquinoline derivatives have potentials as a therapeutic agent for the treatment for melanoma.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5229-5232
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• 2012

The incidence of malignant melanoma increases with age. One significiant effect of aging processes is an accumulation of oxidative damage in the genetical material. In this study, the relationship between malignant melanoma and damage in chromosomes and proliferative effectiveness of human peripheral lymphocytes were investigated by the micronucleus (MN) technique. A total of 15 malignant melanoma patients and appropriately matching 15 healthy controls were involved in the study. MN frequencies and proliferative indexes (PI) after non toxic levels of hydrogen peroxide treatment were also measured to determine damaging effect of oxidative stress in genome in addition to measuring the spontenous levels of micronuclei and PI. The patient group had a significantly higher rate of spontaneous MN than the control group (p<0.01). After treatment with $H_2O_2$, MN frequencies in the patient group was significantly decreased (p<0.01) although there was no difference between the treated and untreated results of control group (p=0.29). There was also difference (p<0.01) between the MN frequencies of the patient and the control group either in the spontaneous levels or in the $H_2O_2$ treated groups. The same significant difference persisted when the PI values were compared between patient and control groups. Increase in the MN frequency in patients could mean the alterations in the chromosomal structure which may lead to the chromosome instability and therefore genetic susceptibility to cancer. This increased number of micronuclei can also be used for cytological marker in identifying high risk cases for malignant melanoma.

• Journal of Microbiology and Biotechnology
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• v.34 no.3
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• pp.589-595
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• 2024

Latilactobacillus curvatus BYB3 (BYB3) is a species of lactic acid bacteria, formerly named Lactobacillus curvatus, which is isolated from kimchi. In this study, the effect of BYB3, Lactobacillus rhamnosus GG, and Lactobacillus acidophilus GP1B strain extracts at various concentrations was examined on B16F10, a mouse melanoma cell line. Cell viability was examined via MTT assay, and the results indicated that compared to the other two probiotics, BYB3 significantly decreased the total percentages of viable cells. The effects of BYB3 on cell migration and proliferation in B16F10 cells were evaluated using wound healing mobility and proliferation assays, respectively; the results indicated that BYB3 inhibits cell migration and proliferation in a concentration-dependent manner. Using human dermal fibroblast cells to investigate BYB3 extract in vivo had no effect on skin-related cells. Nonetheless, the BYB3 extract inhibited tumor growth in a mouse model, as demonstrated by liver slices. Therefore, this suggests that using BYB3 extract to inhibit melanoma may be a novel approach.

• International Journal of Oral Biology
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• v.36 no.3
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• pp.155-162
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• 2011

Eugenol (4-allyl-2-methoxyphenol) is a naturally occurring phenolic compound that is widely used in dentistry as a component of zinc oxide eugenol cement that is commonly applied to the mouth environment. Cisplatin is one of the most potent known anticancer agents and shows significant clinical activity against a variety of solid tumors. This study was undertaken to investigate the synergistic apoptotic effects of co-treatments with eugenol and cisplatin on human melanoma (G361) cells. To investigate whether this co-treatment efficiently reduces the viability of G361 cells compared with each single treatment, an MTT assay was conducted. The induction and augmentation of apoptosis were confirmed by DNA electrophoresis, Hoechst staining and an analysis of DNA hypoploidy. Western blot analysis and immunofluorescent staining were also performed to evaluate the expression levels and the translocation of apoptosis-related proteins following this co-treatment. Furthermore, proteasome activity and mitochondrial membrane potential (MMP) changes were also assayed. The results indicated that a co-treatment with eugenol and cisplatin induced multiple pathways and processes associated with an apoptotic response in G361 cells including nuclear condensation, DNA fragmentation, a reduction in MMP and proteasome activity, the increase and decrease of Bax and Bcl-2, a decreased DNA content, the release of cytochrome c into the cytosol, the translocation of AIF and DFF40 (CAD) into the nucleus, and the activation of caspase-9, caspase-7, caspase-3, PARP and DFF45 (ICAD). In contrast, separate treatments of 300 ${\mu}M$ eugenol or 3 ${\mu}M$ cisplatin for 24 h did not induce apoptosis. Our present data thus suggest that a combination therapy of eugenol and cisplatin is a potential treatment strategy for human melanoma.