• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.6
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• pp.1664-1671
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• 2006

Cisplatin is a anti-neoplastic agent which is commonly used for the treatment of solid tumor. Cisplatin activates multiple signal transduction pathways involved in the stress-induced apoptosis in a variety of cell types. Cytotoxicity of cisplatin was detected in rat mesangial cells and the value of $IC_{50}$ is about 20 ${\mu}M$. The treatment of cisplatin to rat mesangial cells showed the apoptotic bodies and DNA fragmentation. The activation of caspase-3, -8, and -9 and proteolytic cleavage of PARP were observed in the rat mesangial cells treated time-dependently with cisplatin. The activation of ERK, p38 and JNK was also observed in the apoptosis induced by cisplatin in rat mesangial cells. The ethanol extract of Bojungbangam-tang (EBJT), a new hergal prescription composed of nine crude drugs, inhibited cisplatin-induced apoptosis in rat mesangial cells. EBJT reduced sub-G1 peak (apoptotic peak) in cisplatin-treated rat mesangial cells. The cisplatin-induced ERK and JNK activation in rat mesangial cells were blocked by EBJT, but EBJT had no effect on p38 activation. Taken together, these results con suggest that EBJT prevents cisplatin-induced apoptotic cell death in rat mesangial cells through inhibition of ERK and JNK activation.

• Journal of Pharmaceutical Investigation
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• v.34 no.1
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• pp.23-27
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• 2004

The urushiol-ethanol corpuscle of 320 nM in average particle size was prepared and concentrated by ultra homogenization and centrifugation. The cytotoxic profiles of this particle for use as anti-tumor agent have been evaluated in vitro in cultures of human fibroblasts (MRC-9) and celvical carcinoma cells (CUMC-3). The cytotoxicty assays revealed that the inhibitor effect of $10^{-5}$ M urushiol-ethanol particle on the growth of MRC-9 was hardly detected, while CUMC-3 cells exhibited over 50% of growth inhibition under the same conditions. In addition, a clear multiple-unit ladder pater of apoptotic DNA was observed for the urushiol treated CUMC-3 cells. Thus, the results indicated that urushiol inhibited growth of celvical carcinoma cells by inducing apoptosis, which is a mechanism observed with other typical antitumor agents.

• Journal of Microbiology and Biotechnology
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• v.25 no.3
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• pp.418-422
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• 2015

In the course of screening for novel cell cycle inhibitors and apoptotic inducers, CR389, elucidated as 5-(1H-benzoimidazol-2-yl)-1H-pyridin-2-one, was generated as a new hit compound. Flow cytometric analysis and western blots of PA-1 cells treated with $60{\mu}M$ CR389 revealed an appreciable cell cycle arrest at the G2/M phase through direct inhibition of the CDK1 complex. In addition, activation of p53 via phosphorylation at Ser15 and subsequent up-regulation of p21^CIP1 showed that CR389 also induces p53-dependent-p21^CIP1-mediated cell cycle arrest. Furthermore, apoptotic induction in $60{\mu}M$ CR389-treated PA-1 cells is associated with the release of cytochrome c from mitochondria through up-regulation of the proapoptotic Bax protein, which results in the activation of procaspase-9 and -3, and the cleavage of poly(ADP-ribose) polymerase (PARP). Accordingly, CR389 seems to have multiple mechanisms of antiproliferative activity through p53-mediated pathways against human ovarian cancer cells. Therefore, we conclude that CR389 is a candidate therapeutic agent for the treatment of human ovarian cancer via the activation of p53.

• IMMUNE NETWORK
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• v.12 no.3
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• pp.104-112
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• 2012

Silica is one of the most abundant compounds found in nature. Immoderate exposure to crystalline silica has been linked to pulmonary disease and crystalline silica has been classified as a Group I carcinogen. Ultrafine (diameter <100 nm) silica particles may have different toxicological properties compared to larger particles. We evaluated the effect of ultrafine silica nanoparticles on mouse bone marrow-derived dendritic cells (BMDC) and murine dendritic cell line, DC2.4. The exposure of dendritic cells (DCs) to ultrafine silica nanoparticles showed a decrease in cell viability and an induction of cell death in size- and concentration-dependent manners. In addition, in order to examine the phenotypic changes of DCs following co-culture with silica nanoparticles, we added each sized-silica nanoparticle along with GM-CSF and IL-4 during and after DC differentiation. Expression of CD11c, a typical DC marker, and multiple surface molecules such as CD54, CD80, CD86, MHC class II, was changed by silica nanoparticles in a size-dependent manner. We also found that silica nanoparticles affect inflammatory response in DCs in vitro and in vivo. Finally, we found that p38 and NF-${\kappa}B$ activation may be critical for the inflammatory response by silica nanoparticles. Our data demonstrate that ultrafine silica nanoparticles have cytotoxic effects on dendritic cells and immune modulation effects in vitro and in vivo.

• Molecules and Cells
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• v.37 no.7
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• pp.518-525
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• 2014

Gammaherpesvirus (${\gamma}HV$) infection of the central nervous system (CNS) has been implicated in diverse neurological diseases, and murine ${\gamma}HV$-68 (MHV-68) is known to persist in the brain after cerebral infection. The underlying molecular mechanisms of persistency of virus in the brain are poorly understood. Here, we characterized a unique pattern of MHV-68 persistent infection in neuroblastoma cells. On infection with MHV-68, both murine and human neuroblastoma cells expressed viral lytic proteins and produced virions. However, the infected cells survived productive infection and could be cultured for multiple passages without affecting their cellular growth. Latent infection as well as productive replication was established in these prolonged cultures, and lytic replication was further increased by treatment with lytic inducers. Our results provide a novel system to study persistent infection of ${\gamma}HVs$ in vitro following de novo infection and suggest application of MHV-68 as a potential gene transfer vector to the brain.

• The Korean Journal of Cytopathology
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• v.10 no.1
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• pp.67-71
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• 1999

We report a case of 53-year-old man with plasmacytold transitional cell carcinoma of the urinary bladder, which may be confused with plasmacytoma. The patient initially presented with gross hematuria and dysuria for two months. Cystoscopy and radiologic studios revealed multiple intraluminal protruding masses on the urinary bladder invading perivesical fat tissue. After urinary cytologic examination and cystoscopic biopsy, radical cystectomy and pelvic lymph node dissections were done. Urine cytology showed single cells and poorly cohesive cells with round eccentric nuclei, bi-or multi-nucleation, indistinct nucleoli, coarse chromatin, and abundant basophilic cytoplasm within relatively clear background. The cytologic findings of tumor cells were similar to the plasma cells seen in plasmacytoma. The tumor of the bladder was composed on discohesive, individual cancer cells with diffuse pattern that simulated lymphoma or plasmacytoma. Immunohistochemical and electron microscopic studies clearly established the epithelial nature of the neoplasm. Recognition of this plasmacytoid type of transitional cell carcinoma of the urinary bladder can avoid the misdiagnosis.

• BMB Reports
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• v.46 no.2
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• pp.113-118
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• 2013

TTRAP is a multi-functional protein that is involved in multiple aspects of cellular functions including cell proliferation, apoptosis and the repair of DNA damage. Here, we demonstrated that the lentivirus-mediated overexpression of TTRAP significantly inhibited cell growth and induced apoptosis in osteosarcoma cells. The ectopic TTRAP suppressed the growth and colony formation capacity of two osteosarcoma cell lines, U2OS and Saos-2. Cell apoptosis was induced in U2OS cells and the cell cycle was arrested at G2/M phase in Saos-2 cells. Exogenous expression of TTRAP in serum-starved U2OS and Saos-2 cells induced an increase in caspase-3/-7 activity and a decrease in cyclin B1 expression. In comparison with wild-type TTRAP, mutations in the 5'-tyrosyl-DNA phosphodiesterase activity of TTRAP, in particular $TTRAP^{E152A}$, showed decreased inhibitory activity on cell growth. These results may aid in clarifying the physiological functions of TTRAP, especially its roles in the regulation of cell growth and tumorigenesis.

• Proceedings of the Korean Vacuum Society Conference
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• 2014.02a
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• pp.467.1-467.1
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• 2014

Quantum dots (QD) solar cells has received considerable attention due to their potential of improving the overall conversion efficiency by harvesting excess energy via multiple excitons generation (MEG). Although there have been many reports which show MEG phenomena by using optical measurement of quantum dots themselves, carrier multiplication in real QD photovoltaic devices has been sparsely reported due to difficulty in dissociation of excitons and charge collection. In this reports, heterojunction QD solar cells composed of PbS QD monolayer on highly crystalline $TiO_2$ thin films were fabricated by using Langmuir-Blodgett deposition technique to significantly reduce charge recombination at the interfaces between each QD. The PbS CQDs monolayer was characterized by using UV-vis, transmission electron microscopy (TEM) and atomic force microscopy (AFM). The internal quantum efficiency (IQE) for the monolayer QD solar cells was obtained by measurement of external quantum efficiency and determining light absorption efficiency of active layer. Carrier multiplication was observed by measuring IQE greater than 100% over threshold photon energy. Our findings demonstrate that monolayer QD solar cell structure is potentially capable of realizing highly efficient solar cells based on carrier multiplication.

• Biomolecules & Therapeutics
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• v.19 no.1
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• pp.21-26
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• 2011

Ceramide is an important lipid mediator of extracellular signals that control various cellular functions, including apoptosis. In this study, we showed that ceramide induced apoptosis in U373MG human glioblastoma cells associated with G1 cell cycle arrest. Treatment of cells with ceramide increased proapoptotic Bax expression and inhibited the expression of antiapoptotic Bcl-2 and Bcl-xL Ceramide also downregulated cyclin E, cyclin D1, cdk 2, and cdk4 which are involved in regulating cell cycle. In addition, ceramide suppressed phosphorylation of Akt, Bad, p70 S6 kinase, and 4E-BP1, suggesting the involvement of Akt/mTOR signaling pathway. Additionally, okadaic acid, an inhibitor of protein phosphatase 2A, partially blocked the ceramide mediated inhibition of phosphorylation of Akt and 4E-BP1. These results suggest that ceramide induces apoptosis in U373MG glioblastoma cells by regulating multiple signaling pathways that involve cell cycle arrest associated with Akt signaling pathway.

• YAKHAK HOEJI
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• v.47 no.6
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• pp.432-437
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• 2003

It has been known that quercetin, a bioflavonoid widely distributed in fruits and vegetables as dietary-derived flavonoid and exert significant multiple biological effects such as antioxidant and anti-inflammatory, anti-tumor effects. In addition, it has been shown to have a chemoprotective role in cancer, though complex effects on signal transduction involved in cell proliferation and angiogenesis. The present study investigated whether quercetin can enhance antioxidant enzyme activity (glutathione peroxidase: GPx, superoxide dismutase: SOD, catalase: CAT) and regulate the reactive oxygen species (ROS) generation in the presence of vitamin E, L-ascorbic acid, reduced glutathione (GSH) on B16F10 murine melanoma cells. After 48h treatment of cells with quercetin in the presence of vitamin E, L-ascorbic acid, GSH, we measured the cytotoxicities by MTT assay. The cells exhibited a dose-dependent inhibition in their proliferation in the presence of vitamin E, L-ascorbic acid, GSH respectively. We also investigated the effects of antioxidant enzyme activity and ROS generation. The antioxidant enzyme activity of quercetin in the presence of vitamin E was stronger than GSH, L-ascorbic acid, the same treatments decreased ROS generation in B16F10 murine melanoma cells. Taken together, these result demonstrate that the antioxidant effect of quercetin can enhanced in the presence of vitamin E and it might plays an important role in anti-oxidative effects.