• The Journal of Korean Medicine
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• v.25 no.2
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• pp.98-109
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• 2004

Objectives : To evaluate the anti-tumor and synergic effect of Soonkiwhajungtang with doxorubicin. Methods : The inhibitory concentration (IC), $IC_{50}$ and $IC_{90}$ of single use of doxorubicin and Soonkiwhajungtang with their concomitant treatment against MKN-45 (human stomach carcinoma) cell line were observed using MTT (microculture tetrazolium test) assay. In addition, their anti-tumor effects were also observed in xenograft nude mice models against the MKN-45 cell line. Results : Soonkiwhajungtang has only minimal direct anti-tumor effect against MKN-45 cell line but it reduced general depressed signs induced by implantation of the tumor cell lines and increased the total WBC and lymphocyte numbers. Conclusions : It is considered or expected that Soonkiwhajungtang extract reduces the critical toxicity of doxorubicin and has favorable synergic anti-tumor effect when administered concomitantly with doxorubicin.

• Journal of Pharmacopuncture
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• v.19 no.2
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• pp.129-136
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• 2016

Objectives: The crude extracts of Scutellaria barbata D. Don (SB) have traditionally demonstrated inhibitory effects on numerous human cancers both in vitro and in vivo. Gastric cancer is one of the most common types of cancer on world. The authors investigated the effects of an ethanol extract of Scutellaria barbata D. Don (ESB) on the growth and survival of MKN-45 cells (a human gastric adenocarcinoma cell line). Methods: The MKN-45 cells were treated with different concentrations of ESB, and cell death was examined using an MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Analyses of sub-G1 peaks, caspase-3 and -9 activities, and mitochondrial membrane depolarizations were conducted to determine the anti-cancer effects of SB on MKN-45 cells. Also, intracellular reactive oxygen species (ROS) generation was investigated. Results: ESB inhibited the growth of MKN-45 cells, caused cell cycle arrest, and increased the sub-G1 population. In addition, ESB markedly increased mitochondrial membrane depolarization and the activities of caspase-3 and -9. ESB exerted anti-proliferative effects on MKN-45 cells by modulating the mitogen-activated protein kinase (MAPK) signaling pathway and by increasing the generation of ROS. Furthermore, combinations of anti-cancer drugs plus ESB suppressed cell growth more than treatments with an agent or ESB, and this was especially true for cisplatin, etoposide, and doxorubicin. Conclusion: ESB has a dose-dependent cytotoxic effect on MKN-45 cells and this is closely associated with the induction of apoptosis. ESB-induced apoptosis is mediated by mitochondria-, caspase- and MAPK dependent pathways. In addition, ESB enhances ROS generation and increases the chemosensitivity of MKN-45 cells. These results suggest that treatment with ESB can inhibit the proliferation and promote the apoptosis of human gastric adenocarcinoma cells by modulating the caspase-, MAPK- and ROS-dependent pathway.

• Journal of Pharmacopuncture
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• v.15 no.2
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• pp.15-19
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• 2012

The purpose of this study was to investigate the anti-cancer effects of Sophorae Radix (SR) and doxorubicin (DOX) in human gastric and colorectal adenocarcinoma cells. We used the human gastric and colorectal adenocarcinoma cell lines (MKN-45 and WIDR cells, respectively). We examined cell death by using the MTT(3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) assay and the caspase 3 assay with SR. To examine the inhibitory effects of SR, we performed a cell cycle (sub G1) analysis for the MKN-45 and WIDR cells after three days with SR. The reversibility of SR was examined for one-day to five-day treatments with SR. SR inhibited the growth of MKN-45 and WIDR cells in a dosedependent manner. Also, we showed that SR induced apoptosis in MKN-45 and WIDR cells by using the MTT assay, the caspase 3 assay and the sub-G1 analysis. SR combined with DOX markedly inhibited the growth of MKN-45 and WIDR cells compared to SR or DOX alone. After 3 days of treating MKN-45 and WIDR cells with SR, the fraction of cells in the sub-G1 phase was much higher than that of the control group. Our findings provide insights into unraveling the effects of SR on human gastric and colorectal adenocarcinoma cells and into developing therapeutic agents for use against gastric and colorectal adenocarcinomas.

• The Journal of Internal Korean Medicine
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• v.25 no.1
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• pp.92-105
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• 2004

In order to evaluate the anti-tumor and synergic effect of BoJungIkKeeHapDaeChilKi-Tang on doxorubicin, the inhibitory concentration(IC), IC50 and IC90 of single use of doxorubicin and BoJungIkKeeHapDaeChilKi-Tang with their concomitant treatment against MKN-45(Human stomach carcinoma) was observed using MTT(Microculture Tetrazolium test) assay. In addition, their anti-tumor effects were also observed in the xenograft nude mice models agianst MKN-45 cell lines. BoJungIkKeeHapDaeChilKi-Tang has only mimic direct anti-tumor effect against to MKN-45 cell lines but they were decreased general depressed signs induced by implantation of tumor cell lines and increased the total WBC and lymphocyte numbers. So, it is considered or expected that BoJungIkKeeHapDaeChilKi-Tang extracts were reduced by the critical toxicity of doxorubicin and shows favorable synergic effect with doxorubicin and BoJungIkKeeHapDaeChilKi-Tang extracts.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.5
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• pp.367-375
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• 2022

Gastric cancer stem cells (GCSCs) are a major cause of radioresistance and chemoresistance in gastric cancer (GC). Therefore, targeting GCSCs is regarded as a powerful strategy for the effective treatment of GC. Atorvastatin is a widely prescribed cholesterol-lowering drug that inhibits 3-hydroxy-3-methylglutaryl-coenzyme A reductase, a rate-limiting enzyme in the mevalonate pathway. The anticancer activity of atorvastatin, a repurposed drug, is being investigated; however, its therapeutic effect and molecular mechanism of action against GCSCs remain unknown. In this study, we evaluated the anticancer effects of atorvastatin on MKN45-derived GCSCs. Atorvastatin significantly inhibited the proliferative and tumorsphere-forming abilities of MKN45 GCSCs in a mevalonate pathway-independent manner. Atorvastatin induced cell cycle arrest at the G0/G1 phase and promoted apoptosis by activating the caspase cascade. Furthermore, atorvastatin exerted an antiproliferative effect against MKN45 GCSCs by inhibiting the expression of cancer stemness markers, such as CD133, CD44, integrin α6, aldehyde dehydrogenase 1A1, Oct4, Sox2, and Nanog, through the downregulation of β-catenin, signal transducer and activator of transcription 3, and protein kinase B activities. Additionally, the combined treatment of atorvastatin and sorafenib, a multi-kinase targeted anticancer drug, synergistically suppressed not only the proliferation and tumorsphere formation of MKN45 GCSCs but also the in vivo tumor growth in a chick chorioallantoic membrane model implanted with MKN45 GCSCs. These findings suggest that atorvastatin can therapeutically eliminate GCSCs.

• Biomolecules & Therapeutics
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• v.11 no.2
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• pp.91-98
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• 2003

A new series of highly water soluble platinum(II) complexes[Pt(II)(DL-2-hydroxy-3-methylbutyrate)(trans-l-1,2-dimninocyc1ohexane)] (PC-1) and [Pt(II)DL-2-hydroxy-3-methylbutyrate](cis-1,2-diaminocyclohexane)](PC-2) were synthesized and characterized by their elemental analysis and by various spectroscopic techniques [infrared(IR), $^{13}C$-nuclear magnetic resonance (NMR)]. In vitro antitumor activity of new Pt(II)complexes was tested against MKN-45, MKN/ADM and MKN/CDDP human gastric adenocarcinoma cell lines using colorimetric MTT[3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyltetrazoliumbromide] assay for cell survival and proliferation. PC-1 and PC-2 showed active against MKN-45/P, MKN/ADM and MKN/CDDP human gastric cancer cell lines, and the antitumor activity of these compounds were comparable or superior to that of cisplatin. The nephrotoxicities of PC-1 and PC-2 were found quite less then that of cisplatin using MTT and [$^3H$] thymidine uptake tests in rabbit proximal tubule cells, human kidney cortical cells human renal cortical tissues. Based on these results, these novel platinum(II) complex compounds(PC-1 ＆ PC-2) represent a valuable lead in the development of the new anticancer chemotherapeutic agents capable of improving antitumor activity and low nephrotoxicity.

• Food Science and Biotechnology
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• v.18 no.4
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• pp.1019-1021
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• 2009

Antiproliferative activity of the ethanol extract of Atractylodes japonica rhizomes (AJEX) was investigated using methyl thiazolyl tetrazolium (MTT) assays with various cancer cell lines (HL-60, MCF-7, SK-Br-3, MDA-MB-453, HepG2, Hep3B, PC-3, LNCaP, MKN 28, MKN 45, and HT-29 cells). Gastric carcinoma cell lines were the most responsive in terms of cell proliferation. The $IC_{50}$ of MKN 28 and MKN 45 cells were 35.98 and 27.57 ${\mu}g/mL$, respectively. Moreover, gastric carcinoma cells exposed to AJEX underwent apoptosis, as determined by Annexin V binding assay. Compared to respective control level, exposure to the AJEX at each $IC_{50}$ concentration resulted in a remarkable increase in the shift of cell populations. Present results suggest that AJEX possess potential anticancer properties.

• Radiation Oncology Journal
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• v.17 no.1
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• pp.65-69
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• 1999

Purpose : It has been well established that the response of cells and tissues to low LET radiations (X- or gamma-ray) can be enhanced by combining with hyperthermia. However, there has been relatively little work of hyperthermia on the possible modification of either cellular or tissue responses to other types of radiation. So, we investigated the combined effect of fast neutron irradiation and hyperthermia according to the sequence and time interval of the two. Materials and Methods : In MKN-45 cells, a human stomach cancer ceil line, suwiving fractions were measured according to the sequential treatment of 0, 4, 2, 0 hour-intewal for fast neutron irradiation (1.5 Gy) combined with hyperthermia (41 $^{\circ}C$ for 30 min or 43$^{\circ}C$ for 30 min). Results : D$_{0}$ and n of MKN-45 for neutron were 0.8 Gy and 2.5, respectively. The surviving fraction by 1.5 Gy of neutron was 0.36$\pm$0.34. Interacting powers were mostly ranged between 1 and 2, but they were 3.0 and 2.7, respectively for hyperthermia (41 $^{\circ}C$ for 30 min) fellowed by neutron irradiation 6 and 4 hours later. Conclusion : The combined effect of fast neutron (1.5 Gy) and hyperthermia (41 $^{\circ}C$ or 43$^{\circ}C$ for 30min) is largely independently additive. Preceding mild hyperthermia (41 $^{\circ}C$ for 30 min) 4 or 6 hours before neutron may cause decreased sensitivity to subsequent neutron irradiation.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.4
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• pp.359-366
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• 2001

We have synthesized a novel platinum(II) coordination complex containing cis-1,2-diaminocyclohexane (DACH) as a carrier ligand and 1,3-dichloropropane (DCP) as a leaving group. A new series of [Pt(cis- DACH)(DCP)](PC) was evaluated for its cytotoxic activity on MKN-45 human gastric adenocarcinoma cells and normal primary cultured kidney cells. The new platinum complex has demonstrated high efficacy in the cytotoxicity against MKN-45/P, MKN-45/ADM and MKN-45/CDDP cell-lines. The cytotoxicity of PC against rabbit proximal renal tubular cells, human renal cortical cells and human renal cortical tissues, determined by MTT assay, the $[^3H]-thymidine$ uptake and glucose consumption tests, was found to be quite less than those of cisplatin. Based on these results, this novel platinum(II) coordination complex appears to be better for improving antitumor activities with low nephrotoxicity and is a valuable lead in the development of new, clinically available anticancer chemotherapeutic agents.

• Journal of Microbiology and Biotechnology
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• v.12 no.5
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• pp.746-752
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• 2002

The purpose of the present study was to examine the antagonistic activities of Enterococcus faecalis strain PL9003 (PL9003) on Helicobacter pylori. This strain was isolated from infant feces and found to inhibit both the growth of H. pylori and its in vitro adherence to the human gastric cell line MKN-45. The binding of PL9003 to MKN-45 was observed under a light microscope after Cram staining and under a scanning electron microscope. When detected with an FITC-conjugate antibody, both viable and nonviable PL9003 were found to decrease the number of H. pylori bound to MKN-45. When detected by an enzyme-linked immunoabsorbent assay, about 70% of the H. pylori bound on MKN-45 disappeared with the four-1314 addition of viable or nonviable PL9003. The spent culture supernatant (SCS) of PL9003 also decreased the viability of H pylori even after neutralization and pepsin treatment. The above results suggest that PL9003 has a potential as a new probiotic for the stomach.