• The Korean Journal of Physiology and Pharmacology
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• v.16 no.1
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• pp.11-16
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• 2012

Cancer stem cells (CSCs) are often characterized by the elevated expression of drug-resistance related stem-cell surface markers, such as CD133 and ABCG2. Recently, we reported that CSCs have a high level of expression of the IL-6 receptor (IL-6R). The purpose of this study was to investigate the effect of anticancer drugs on the expression of the drug resistance-related cancer stem cell markers, ABCG2, IL-6R, and CD133 in non-small cell lung cancer (NSCLC) cell lines. A549, H460, and H23 NSCLC cell lines were treated with the anticancer drugs 5-fluorouracil (5-FU; $25{\mu}g/ml$) and methotrexate (MTX; $50{\mu}g/ml$), and the expression of putative CSC markers was analyzed by fluorescent activated cell sorter (FACS) and the gene expression level of abcg2, il-6r and cd133 by reverse transcriptase-polymerase chain reaction (RT-PCR). We found that the fraction of ABCG2-positive(+) cells was significantly increased by treatment with both 5-FU and MTX in NSCLC cells, and the elevation of abcg2, il-6r and cd133 expressions in response to these drugs was also confirmed using RT-PCR. Also, the number of IL-6R(+) cells was increased by MTX in the 3 cell lines mentioned and increased by 5-FU in the H460 cell line. The number of CD133(+) cells was also significantly increased by both 5-FU and MTX treatment in all of the cell lines tested. These results indicate that 5-FU and MTX considerably enhance the expression of drug-resistance related CSC markers in NSCLC cell lines. Thus, we suggest that antimetabolite cancer drugs, such as 5-FU and MTX, can lead to the propagation of CSCs through altering the expression of CSC markers.

• Korean Journal of Pharmacognosy
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• v.45 no.2
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• pp.174-180
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• 2014

D-Pinitol, an anti-diabetic substance, is a naturally occurring compound found in legumes. In this study, we investigated the inhibitory effect of D-pinitol on growth and recurrence of breast cancer. When D-pinitol was treated on MDA-MB-231 or MCF-7 breast cancer cells, it was observed that the viability of the two cancer cell lines was reduced in MTT assay. In order to examine the effect on the growth of breast tumor, mouse xenograft assay was carried out. On day 0, nine millions cells of MDA-MB-231 were injected subcutaneously into nude mouse and D-pinitol was administered orally at the dose of 500 mg/kg or 1000 mg/kg body weight for consecutive 45 days. Tumor size was reduced in dose-dependent manner upto 95.4% in 1000 mpk-treated group, compared with the non-treated control group. When D-pinitol was co-administrated with $4{\mu}g$ of doxorubicin, recurrence of breast tumor was delayed by two weeks, compared with the mouse group of doxorubicin monotherapy. Consistent with this data, it was observed that the population of cancer stem cells (CSCs), responsible for recurrence of cancer, within tumor mass was significantly reduced. Taken together, D-pinitol inhibits the growth of breast cancer and relapse of the tumor by suppressing the proliferation of CSCs.

• Journal of Life Science
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• v.26 no.10
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• pp.1214-1217
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• 2016

Rebamipide is a mucosal-protective antiulcer drug, but its mechanism of action in gastric cancer remains elusive. CagA, a major virulence factor of Helicobacter pylori (H. pylori), is associated with the risk of gastric cancer. CagA protein is injected into gastric epithelial cells and deregulates a variety of cellular signaling molecules. CagA from H. pylori induces phospholipase D1 (PLD1) expression through NFκB activation in gastric epithelial cells, followed by invasion and proliferation of gastric epithelial cancer cells. Infection with cagA-positive H. pylori and expression of CagA enhances the binding of NFκB to the PLD1 promoter. Rebamipide abolishes H. pylori cagA-induced PLD1 expression via inhibition of binding of NFκB to the PLD1 promoter and also inhibits PLD activity. Moreover, rebamipide abolishes H. pylori CagA-induced β-catenin and the expression of a target cancer stem cell (CSC) marker gene via upregulation of miRNA-320a and -4496, followed by attenuation of self-renewal capacity of H. pylori CagA-infected gastric CSCs. In addition, rebamipide increases the chemosensitivity of CagA-expressed gastric CSCs and suppresses gastric carcinogenesis. Thus, it is speculated that rebamipide might show a potent efficacy as chemotherapeutic drug against gastric cancer cells. In this review, we summarizes recent results regarding the novel insights for the efficacy of rebamipide in gastric cancer cells.

• Korean Journal of Veterinary Research
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• v.58 no.4
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• pp.201-209
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• 2018

Canine mammary tumors are among the most frequently observed cutaneous tumors in female dogs. Cancer stem cells (CSCs), referred to as tumor-initiating cells, are thought to have properties similar to normal stem cells such as the ability to self-renewal and to differentiate into various cell types. Biological understanding of CSCs and the critical pathways involved in their maintenance are important in research and therapy for mammary tumors. We conducted the present study on sphere formation from REM134 cells by using methylcellulose to produce tumorspheres on a large scale and compared the specific markers of the spheres-formed and plating-cultured REM134 cells. The results revealed that the tumorspheres cultured in methylcellulose had higher seeding density and improved morphology compared to those produced in normal sphere formation medium. Expression levels of stemness markers and CSC-related markers were higher in tumorsphere-forming cells than in plating-cultured cells. Subsequently, we transplanted the tumorsphere-forming and plating-cultured cells into female nude mice to examine their tumorigenic potential. Tumor volume increased rapidly in mice transplanted with tumorsphere-derived cells compared to plating-cultured cells. We observed a novel sphere-forming condition for REM134 cells and showed that REM134 cell tumorspheres can exhibit improved CSC properties.

• Current Photovoltaic Research
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• v.11 no.2
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• pp.39-43
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• 2023

Carrier-selective contacts (CSCs) solar cells are considerably attractive on highly efficient crystalline silicon heterojunction (SHJ) solar cells due to their advantages of high thermal tolerance and the simple fabrication process. CSCs solar cells require a hole selective contact (HSC) layer that selectively collects only holes. In order to selectively collect holes, it must have a work function characteristic of 5.0 eV or more when contacted with n-type Si. The VO_x, NiO_x, and CuI_x thin films were fabricated and analyzed respectively to confirm their potential usage as a hole-selective contact (HSC) layer. All thin films showed characteristics of band-gap engergy > 3.0 eV, work function > 5.0 eV and minority carrier lifetime > 1.5 ms.

• Restorative Dentistry and Endodontics
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• v.47 no.1
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• pp.10.1-10.11
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• 2022

Objectives: This study aimed to investigate the color stability, solubility, and surface characteristics of 3 calcium silicate-based cements (CSCs) after immersion in different solutions. Materials and Methods: ProRoot white mineral trioxide aggregate (MTA), Biodentine, and Endosequence Root Repair Material (ERRM) were placed in cylindrical molds and stored at 37℃ for 24 hours. Each specimen was immersed in distilled water, 5% sodium hypochlorite (NaOCl), 2% chlorhexidine, or 0.1% octenidine hydrochloride (OCT) for 24 hours. Color changes were measured with a spectrophotometer. Solubility was determined using an analytical balance with 10^-5 g accuracy. The surface characteristics were analyzed using scanning electron microscopy and energy-dispersive spectroscopy. Data were analyzed using 2-way analysis of variance, the Tukey test, and the paired t-test. Results: MTA exhibited significant discoloration in contact with NaOCl (p < 0.05). White precipitation occurred on the surfaces of Biodentine and ERRM after contact with the solutions, and none of the materials presented dark brown discoloration. All materials showed significant solubility after immersion in the solutions (p < 0.05), irrespective of the solution type (p > 0.05). The surface topography and elemental composition of the samples showed different patterns of crystal formation and precipitation depending on the solution type. Conclusions: All materials presented some amount of solubility and showed crystal precipitation after contact with the solutions. Biodentine and ERRM are suitable alternatives to ProRoot MTA as they do not exhibit discoloration. The use of OCT can be considered safe for CSCs.

• Journal of the korean academy of Pediatric Dentistry
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• v.50 no.2
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• pp.217-228
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• 2023

This study aimed to compare the physical properties of 4 kinds of calcium silicate-based cements (CSCs): 2 kinds of powder-liquid mix type (RetroMTA^® [RTMX] and Endocem^® MTA Zr [EZMX]) and 2 kinds of premixed type (Well-Root^TMPT [WRPR] and Endocem^® MTA premixed [ECPR]) CSCs, respectively. Further, we assessed the setting times, solubility values, and compressive strengths of the cements. The shortest setting time was observed for EZMX (123.33 ± 5.77 seconds), followed by RTMX (146.67 ± 5.77 seconds), ECPR (260.00 ± 17.32 seconds), and WRPR (460.00 ± 17.32 seconds), respectively. The highest solubility was observed for WRPR (9.01 ± 0.55%), followed by RTMX (2.17 ± 0.07%), EZMX (0.55 ± 0.03%), and ECPR (0.17 ± 0.03%). Furthermore, the highest compressive strength was observed for ECPR (76.67 ± 25.67 Mpa), followed by WRPR (38.39 ± 7.25 Mpa), RTMX (35.07 ± 5.34 Mpa), and EZMX (4.07 ± 0.60 Mpa). In conclusion, the premixed type CSCs (WRPR and ECPR) exhibited longer setting times compared to the powder-liquid mix type CSCs (EZMX and RTMX). The solubility test showed that ECPR had the lowest solubility while WRPR had the highest solubility, with a statistically significant difference between them (p < 0.0083). Additionally, the compressive strength test showed that ECPR had the highest compressive strength, while EZMX had the lowest compressive strength, also with a statistically significant difference between them (p < 0.0083). ECPR is a promising material as it is premixed, eliminating the need for mixing time, and it has also demonstrated improved solubility and compressive strength, making it a potentially favorable option for clinical use.

• Molecules and Cells
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• v.37 no.7
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• pp.547-553
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• 2014

Glioblastoma multiforme (GBM) is one of the most common brain malignancies and has a very poor prognosis. Recent evidence suggests that the presence of cancer stem cells (CSC) in GBM and the rare CSC subpopulation that is resistant to chemotherapy may be responsible for the treatment failure and unfavorable prognosis of GBM. A garlic-derived compound, Z-ajoene, has shown a range of biological activities, including anti-proliferative effects on several cancers. Here, we demonstrated for the first time that Z-ajoene specifically inhibits the growth of the GBM CSC population. CSC sphere-forming inhibition was achieved at a concentration that did not exhibit a cytotoxic effect in regular cell culture conditions. The specificity of this inhibitory effect on the CSC population was confirmed by detecting CSC cell surface marker CD133 expression and biochemical marker ALDH activity. In addition, stem cell-related mRNA profiling and real-time PCR revealed the differential expression of CSC-specific genes, including Notch, Wnt, and Hedgehog, upon treatment with Z-ajoene. A proteomic approach, i.e., reverse-phase protein array (RPPA) and Western blot analysis, showed decreased SMAD4, p-AKT, 14.3.3 and FOXO3A expression. The protein interaction map (http://string-db.org/) of the identified molecules suggested that the AKT, ERK/p38 and $TGF{\beta}$ signaling pathways are key mediators of Z-ajoene's action, which affects the transcriptional network that includes FOXO3A. These biological and bioinformatic analyses collectively demonstrate that Z-ajoene is a potential candidate for the treatment of GBM by specifically targeting GBM CSCs. We also show how this systemic approach strengthens the identification of new therapeutic agents that target CSCs.

• Steel and Composite Structures
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• v.27 no.1
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• pp.123-133
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• 2018

Steel-concrete-steel (SCS) sandwich composite structure with corrugated-strip connectors (CSC) has the potential to be used in buildings and offshore structures. In this structure, CSCs are used to bond steel face plates and concrete. To overcome executive problems, in the proposed system by the authors, shear connectors are one end welded as double skin composites. Hence, this system double skin with corrugated-strip connectors (DSCS) is named. In this paper, finite element model (FEM) of push-out test was presented for the basic component of DSCS. ABAQUS/Explicit solver in ABAQUS was used due to the geometrical complexity of the model, especially in the interaction of the shear connectors with concrete. In order that the explicit analysis has a quasi-static behavior with a proper approximation, the kinetic energy (ALLKE) did not exceed 5% to 10% of the internal energy (ALLIE) using mass-scaling. The FE analysis (FEA) was validated against those from the push-out tests in the previous work of the authors published in this journal. By comparing load-slip curves and failure modes, FEMs with suitable analysis speed were consistent with test results.

• BMB Reports
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• v.51 no.11
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• pp.596-601
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• 2018

Colon cancer is one of the most lethal and common malignancies worldwide. STK899704, a novel synthetic agent, has been reported to exhibit anticancer effects towards numerous cancer cells. However, the effect of STK899704 on the biological properties of colon cancer, including cancer cell migration and cancer stem cells (CSCs), remains unknown. Here, we examined the inhibitory effect of STK899704 on cell migration and CSC stemness. In the wound healing assay, STK899704 significantly inhibited the motility of colon cancer cells. Furthermore, STK899704 downregulated the mRNA expression levels of the cell migration mediator focal adhesion kinase (FAK). STK899704 also suppressed mitogen-activated protein kinase kinase and extracellular signal-regulated kinase, which are downstream signaling molecules of FAK. Additionally, STK899704 inhibited stemness gene expression and sphere formation in colon cancer stem cells. These results suggest that STK899704 can be used to treat human colon cancer.