• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.631-637
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• 2013

Luteolin is a naturally occurring flavonoid present in many plants with diverse applications in pharmacology. Despite several studies elucidating its significant anti-cancer activity against various cancer cells, the mechanism of action in skin cancer is not well addressed. Hence, we investigated the effects of luteolin in HaCaT (human immortalized keratinocytes) and A375 (human melanoma) cells. The radical scavenging abilities of luteolin were determined spectrophotometrically, prior to a cytotoxic study (XTT assay). Inhibitory effects were assessed by colony formation assay. Further, the capability of luteolin to induce cell cycle arrest and apoptosis were demonstrated by flow cytometry and cellular DNA fragmentation ELISA, respectively. The results revealed that luteolin possesses considerable cytotoxicity against both HaCaT and A375 cells with $IC_{50}$ values of 37.1 ${\mu}M$ and 115.1 ${\mu}M$, respectively. Luteolin also inhibited colony formation and induced apoptosis in a dose and time-dependent manner by disturbing cellular integrity as evident from morphological evaluation by Wright-Giemsa staining. Accumulation of cells in G2/M (0.83-8.14%) phase for HaCaT cells and G0/G1 (60.4-72.6%) phase for A375 cells after 24 h treatment indicated cell cycle arresting potential of this flavonoid. These data suggest that luteolin inhibits cell proliferation and promotes cell cycle arrest and apoptosis in skin cancer cells with possible involvement of programmed cell death, providing a substantial basis for it to be developed into a potent chemopreventive template for skin cancer.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.4
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• pp.333-344
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• 2023

Hepatocellular carcinoma (HCC) is a prevalent malignant tumor with high fatality. It has yet to be reported whether circ-SNX27 can affect the progression of HCC. This study attempted to analyze circ-SNX27's precise role and underlying mechanisms in HCC. HCC cell lines and tumor specimens from HCC patients were analyzed using quantitative real-time PCR and Western blotting to quantify the expressions of circ-SNX27, miR-375, and ribophorin I (RPN1). Cell invasion and cell counting kit 8 experiments were conducted for the evaluation of HCC cell invasion and proliferation. Caspase-3 Activity Assay Kit was utilized to gauge the caspase-3 activity. Luciferase reporter and RNA immunoprecipitation assays were executed to ascertain the relationships among miR-375, circ-SNX27, and RPN1. To determine how circ-SNX27 knockdown affects the growth of HCC xenografts in vivo, tumor-bearing mouse models were constructed. Elevated expressions of circ-SNX27 and RPN1 as well as a reduced miR-375 expression were observed among HCC cells and HCC patient tumor specimens. Knocking-down circ-SNX27 in HCC cells abated their proliferative and invasive abilities but raised their caspase-3 activity. Moreover, the poor levels of circ-SNX27 inhibited HCC tumor growth among the mice. Circ-SNX27 enhanced RPN1 by competitively binding with miR-375. Silencing miR-375 in HCC cells promoted their malignant phenotypes. Nonetheless, the promotive effect of miR375 silencing was reversible via the knockdown of circ-SNX27 or RPN1. This research demonstrated that circ-SNX27 accelerated the progression of HCC by modulating the miR-375/RPN1 axis. This is indicative of circ-SNX27's potential as a target for the treatment of HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.699-705
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• 2015

Vemurafenib has recently been used as drug for treatment of melanomas with $BRAF^{V600E}$ mutation. Unfortunately, treatment with only vemurafenib has not been sufficiently effective, with recurrence after a short period. In this study, three vemurafenib-resistant $BRAF^{V600E}$ melanoma cell lines, $A375P^R$, $A375M^R$ and SKMEL-$28^R$, were established from the original A375P, A375M and SKMEL-28 cell lines. Examination of the molecular mechanisms showed that the phosphorylation levels of MEK and ERK, which play key roles in the RAS/RAF/MEK/ERK signaling pathway, were reduced in these three cell lines, with increased phosphorylation levels of pAKTs limited to SKMEL-$28^R$ cells. Treatment of SKMEL-$28^R$ cells with 100 nM paclitaxel resulted in increased apoptosis and decreased cellular proliferation, invasion and colony formation via reduction of expression levels of EGFR and pAKTs. Moreover, vemurafenib-induced pAKTs in SKMEL-$28^R$ were decreased by treatment with an AKT inhibitor, MK-2206. Taken together, our results revealed that resistance mechanisms of $BRAF^{V600E}$-mutation melanoma cells to vemurafenib depended on the cell type. Our results suggested that paclitaxel should be considered as a drug in combination with vemurafenib to treat melanoma cells.

• Toxicological Research
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• v.12 no.1
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• pp.93-99
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• 1996

The effect of KTC-1, a new semisynthetic rifamycin antituberculous drug, on general toxicity, reproductive capability and fetal development was investigated in Sprague-Dawley rats. Male rats were administered KTC-1 with mashed feed from 63 days before mating to the end of mating period, and female rats were given from 14 days before mating to day 7 of gestation at dose levels of 0, 375, 750, and 1,500 ppm. The females were sacrificed on day 21 of gestation for examination of their fetuses. At 1,500 ppm, a reduction in body weight gain and testis atrophy were observed in male rats. Histological examination revealed testicular atrophy, absence or decrease of germinal cells, and vacuolization of Sertoli cells in testis. A reduction in body weight gain, a decrease in food consumption were found in female rats. In addition, decreases in the number of corpora lutea, iraplantations, and the litter size of live fetuses were seen. Mating, fertility, and pregnancy performances were also affected. There were no external abnormalities observed by examination of fetuses. At 750 ppm, a reduction in the body weight gain of male and female rats and decreases in the number of implantations and litter size were found. At 375 ppm, no treatment-related effects were observed. The results suggest that the no-effect dose levels (NOELs) of KTC-1 are 375 ppm for males and females on general toxicity, 750 ppm for males and females on reproductive capability, and 375 ppm for fetuses on embryonic development.

• Nutrition Research and Practice
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• v.5 no.5
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• pp.375-380
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• 2011

This study investigated the effects of inorganic sulfur on metastasis in MDA-MB-231 human breast cancer cells. MDA-MB-231 cells were cultured in the absence or presence of various concentrations (12.5, 25, or 50 ${\mu}mol$/L) of inorganic sulfur. Cell motility, invasion, and the activity and mRNA expression of matrix metalloproteases (MMPs) were examined. Numbers of viable MDA-MB-231 cells did not differ by inorganic sulfur treatment from 0 to 50 ${\mu}mol$/L within 48 h. Inorganic sulfur significantly decreased cell motility and invasion in the MDA-MB-231 cells in a dose-dependent manner (P<0.05), as determined using a Boyden chamber assay and a Matrigel chamber. The activities of MMP-2 and MMP-9 were significantly reduced by inorganic sulfur in a dose-dependent manner (P<0.05). The inorganic sulfur also significantly inhibited MMP-2 and MMP-9 expression in the cells (P<0.05). These data suggest that inorganic sulfur can suppress cancer cell motility and invasion by inhibiting MMP-2 and MMP-9 activity and gene expression in MDA-MB-231 cells.

• Current Optics and Photonics
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• v.6 no.4
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• pp.375-380
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• 2022

We demonstrate two types of light field displays based on waveguide grating coupler arrays: a line beam type and a point source type. Ultra violet imprinting of an array of diffractive nanograting cells on the top surface of a 50-㎛-thin slab waveguide can deliver a line beam or a point beam to a multidirectional light field out of the waveguide slab. By controlling the grating vectors of the nanograting cells, the waveguide modes are externally coupled to specific viewing angles to create a multidirectional light field display. Nanograting cells with periods of 300 nm-518 nm and slanted angles of -8.5°~+8.5° are fabricated by two-beam interference lithography on a 40 mm × 40 mm slab waveguide for seven different viewpoints. It is expected that it will be possible to realize a very thin and flexible panel that shows multidirectional light field images through the waveguide-type diffraction display.

• Journal of the Korean Applied Science and Technology
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• v.26 no.1
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• pp.29-37
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• 2009

This study is focused on the synthesis of urea and amide derivatives particularly, since the amide moiety is an essential binding group at the binding site. Urea derivatives 3-7 and 13-14 were obtained by reaction of 2-aminopyrimidines and other amines with diverse isocyanates in pyridine as a solvent under reflux. The urea derivatives were obtained in low yield because of the highly electron deficient nature of the amino group of the 2-aminopyrimidine. Amide derivatives 8-10 were obtained in moderate yields by reaction of compound 1 with aryl chloride derivatives. Also, arylamine 11 was synthesized by Buchwald-Hartwig amination in moderate yields. Most of the compound did not show good activity against A375P melanoma cells, compared with Sorafenib as control compound.

• International Journal of Oral Biology
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• v.42 no.3
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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.

• Molecules and Cells
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• v.41 no.2
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• pp.119-126
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• 2018

microRNA (miR)-612 shows anticancer activity in several types of cancers, yet its function in melanoma is still unclear. This study was undertaken to investigate the expression of miR-612 and its biological relevance in melanoma cell growth, invasion, and tumorigenesis. The expression and prognostic significance of miR-612 in melanoma were examined. The effects of miR-612 overexpression on cell proliferation, colony formation, tumorigenesis, and invasion were determined. Rescue experiments were conducted to identify the functional target gene(s) of miR-612. miR-612 was significantly downregulated in melanoma tissues compared to adjacent normal tissues. Low miR-612 expression was significantly associated with melanoma thickness, lymph node metastasis, and shorter overall, and disease-free survival of patients. Overexpression of miR-612 significantly decreased cell proliferation, colony formation, and invasion of SK-MEL-28 and A375 melanoma cells. In vivo tumorigenic studies confirmed that miR-612 overexpression retarded the growth of A375 xenograft tumors, which was coupled with a decline in the percentage of Ki-67-positive proliferating cells. Mechanistically, miR-612 targeted Espin in melanoma cells. Overexpression of Espin counteracted the suppressive effects of miR-612 on melanoma cell proliferation, invasion, and tumorigenesis. A significant inverse correlation (r = -0.376, P = 0.018) was observed between miR-612 and Espin protein expression in melanoma tissues. In addition, overexpression of miR-612 and knockdown of Espin significantly increased the sensitivity of melanoma cells to doxorubicin. Collectively, miR-612 suppresses the aggressive phenotype of melanoma cells through downregulation of Espin. Delivery of miR-612 may represent a novel therapeutic strategy against melanoma.