• Journal of Environmental Science International
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• v.16 no.2
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• pp.219-225
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• 2007

Endocrine disrupting compounds (EDC's) are chemicals that either mimic endogenous hormones interfering with pharmacokinetics or act by other mechanisms. Some endocrine disrupters were reported to be chemical substances that cause apoptosis in cells. A number of reports have indicated that 1,3-DCP, one of the EDC's may act as an endocrine disrupter and also has possible carcinogenic effects. 1,3-DCP, present in commercial protein hydrolysates used for human nutrition, are genotoxic and 1,3-dichloro-2-propanol induced tumors in rats. In the present study, it was investigated whether 1,3-DCP induces ROS generation and apotosis in A549 adenocarcinoma cells. Here we show that 1,3-DCP inhibits the growth of lung cancer cell lines and generates reactive oxygen species (ROS), a major cause of DNA damage and genetic instability, It was investigated that 1,3-DCP increases G1 phase cells after 12 hours, thereafter abruptly draws A549 cells to G0 state after 24 hours by flow cytometric analysis. 1,3-DCP induces p53 and $p21^{Cip1/WAF1}$ activation time- and dose-dependently by 24 hours, while the level $p21^{Cip1/WAF1}$ was decreased after 48 hours. These results suggest that 1,3-DCP, an EDC's generates ROS and regulates genes involved with cell cycle and apoptosis.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2325-2331
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• 2013

Objective: To detect effects of plumbagin on proliferation and apoptosis in non-small cell lung cancer cell lines, and investigate the underlying mechanisms. Materials and Methods: Human non-small cell lung cancer cell lines A549, H292 and H460 were treated with various concentrations of plumbagin. Cell proliferation rates was determined using both cell counting kit-8 (CCK-8) and clonogenic assays. Apoptosis was detected by annexin V/propidium iodide double-labeled flow cytometry and TUNEL assay. The levels of reactive oxygen species (ROS) were detected by flow cytometry. Activity of NF-${\kappa}B$ was examined by electrophoretic mobility shift assay (EMSA) and luciferase reporter assay. Western blotting was used to assess the expression of both NF-${\kappa}B$ regulated apoptotic-related gene and activation of p65 and $I{\kappa}B{\kappa}$. Results: Plumbagin dose-dependently inhibited proliferation of the lung cancer cells. The IC50 values of plumbagin in A549, H292, and H460 cells were 10.3 ${\mu}mol/L$, 7.3 ${\mu}mol/L$, and 6.1 ${\mu}mol/L$ for 12 hours, respectively. The compound concentration-dependently induced apoptosis of the three cell lines. Treatment with plumbagin increased the intracellular level of ROS, and inhibited the activation of NK-${\kappa}B$. In addition to inhibition of NF-${\kappa}B$/p65 nuclear translocation, the compound also suppressed the degradation of $I{\kappa}B{\kappa}$. ROS scavenger NAC highly reversed the effect of plumbagin on apoptosis and inactivation of NK-${\kappa}B$ in H460 cell line. Treatment with plumbagin also increased the activity of caspase-9 and caspase-3, downregulated the expression of Bcl-2, upregulated the expression of Bax, Bak, and CytC. Conclusions: Plumbagin inhibits cell growth and induces apoptosis in human lung cancer cells through an NF-${\kappa}B$-regulated mitochondrial-mediated pathway, involving activation of ROS.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.86-86
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• 2003

In a continuous effort to develop novel anticancer agents we newly synthesized and evaluated the antitumor activity of nucleoside analogues. One analogue, 4 - ［2-Chlor-6- (3-iodo- benzy lamino) -purin -9-yl］- 2,3-dihydroxy-cyclopentanecarbo xylic acid methylamide (LJ-331), has been shown to exert a potent inhibition of human cancer cell growth in vitro including human lung (A549), stomach (SNU-638) and leukemia (HL-60) cancer cells. Following mechanism of action study revealed that LJ - 331induces cell cycle arrest at the G1 phase in HL-60 cells and evokes apoptotic phenomena such as an increase in DNA ladder intensity and chromatin condensation by a dose- and time-dependent manner. LJ-331 also activated the caspase-3 activity in HL-60. This result suggests that the growth inhibition of human cancer cells by LJ-331 might be related to the cell cycle arrest and induction of apoptosis.

• Biomedical Science Letters
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• v.28 no.4
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• pp.247-259
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• 2022

Immunotherapy, which uses an immune mechanism in the body, has received considerable attention for cancer treatment. Suberoylanilide hydroxamic acid (SAHA), also known as a histone deacetylase inhibitor (HDACi), is used as a cancer treatment to induce active immunity by increasing the expression of T cell-induced chemokines. However, this SAHA treatment has the disadvantage of causing PD-L1 overexpression in tumor cells. In this study, we prevented PD-L1 overexpression by blocking the PD-1/PD-L1 pathway using PD-L1 siRNA. We designed two types of liposomes, the neutral lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholin (POPC) for SAHA, and 1,2-dioleoyl-3-trimethylammoniumpropane (DOTAP) for siRNA. To effectively target PD-L1 in cancer cells, we conjugated PD-L1 antibody with liposomes containing SAHA or PD-L1 siRNA. These immunoliposomes were also evaluated for cytotoxicity, gene silencing, and T-cell-induced chemokine expression in human non-small cell lung cancer A549 cells. It was confirmed that the combination of the two immunoliposomes increased the cancer cell suppression efficacy through Jurkat T cell induction more than twice compared to SAHA alone treatment. In conclusion, this combination of immunoliposomes containing a drug and nucleic acid has promising therapeutic potential for non-small-cell lung carcinoma (NSCLC).

• Journal of the Korean Society of Food Science and Nutrition
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• v.35 no.10
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• pp.1291-1296
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• 2006

This study was performed to determine the antimutagenic and anticancer effects of Fagopyrum esculentum Moenech noodles (FEMN) extracts using Ames test and cytotoxicity, respectively. FEMN made buckwheat wet noodles (BWN), buckwheat extruded noodles (BEN) and buckwheat dehydrated noodles (BDN) by 60% buckwheat flour and 70% buckwheat flour. The inhibitory effects of FEMN extracts on cell proliferation in A549, Hep3B, MCF-7, AGS and HeLa were investigated by SRB assay. The cytotoxic effects of FEMN against the cell lines with human lung carcinoma (A549), human gastric carcinoma (AGS), human hepatocellular carcinoma (Hep3B), human cervical adenocarcinoma (HeLa) and human breast adenocarcinoma (MCF-7) were inhibited with the increase of the extract concentration. The treatment of 1.0 mg/mL FEMN of 60% BEN extracts showed strong cytotoxicities of 74.7%, 75.3% and 70.5% against AGS, A549 and HeLa, respectively. The inhibition rate of 70% BWN of FEMN extracts in the S. Typhimurium TA100 strain showed 41% against the mutagenesis induced by MNNG. The inhibition rate of 70% BEN of FEMN extracts in the S. Typhimurium TA98 strain showed 45% against the mutagenesis induced by 4NQO.

• Tuberculosis and Respiratory Diseases
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• v.48 no.2
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• pp.223-235
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• 2000

Background: Liquid ventilation is associated with decreased inflammatory response in an injured lung. This study was performed to investigate if whether perfluorocarbon(PFC) can decrease chemokine expression in airway epithelial cells. Methods: A549 cells were used for airway epithelial cells and perfluorodecalin for PFC. To expose cells to PFC, lower chamber of Transwell$^{(R)}$plate was used. This study was performed in two parts. In the first part, we examined whether PFC could decrease chemokine expression in airway epithelial cells through inhibition of other inflammatory cells. Peripheral blood mononuclear cells(PBMC's) were isolated and stimulated with lipopolysaccharide(LPS, 10 ${\mu}g/mL$) for 24 hours with or without exposure to PFC. Then A549 cells were stimulated with conditioned media(CM) containing the culture supernatants of PBMC. After 24 hours, the expressions of interleukin-8(IL-8) and RANTES were measured. In the second part of the study, we studied whether PFC could directly suppress chemokine expression in airway epithelial cells. A549 cells were stimulated for 24 hours with interleukin-l$\beta$ and/or tumor necrosis factor-$\alpha$ with or without exposure to PFC, and then the chemokine expression was measured. Northern analysis was used to measure the mRNA expression, and ELISA was used for immunoreactive protein measurements in culture supernatant. Results: 1. IL-8 and RANTES mRNA expression and immunoreactive protein production were increased significantly by CM from LPS-stimulated PBMC in A459 cells compared to with CM from unstimulated PBCM (p<0.05), but exposure of PFC had no significant effect on either mRNA expression or immunoreactive protein expression. 2. IL-8 and RANTES mRNA expression and immunoreactive protein production were increased significantly by IL-1$\beta$ and TNF-$\alpha$ in A549 cells(p<0.05), but exposure of PFC had no significant effect on neither either mRNA expression nor immunoreactive protein production. Conclusion : Decreased chemokine expression of airway epithelial cells may not be involved in decreased inflammatory response observed in liquid ventilation. Further studies on possible mechanisms of decreased inflammatory response are warranted.

• Environmental Analysis Health and Toxicology
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• v.19 no.1
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• pp.59-64
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• 2004

Metallothionein gene expression of diesel exhaust particles (DEP) was investigated in human lung epithelial cell line. DEP was collected from diesel motor bus and soluble fraction in water was obtained. Cells, grown to near confluence, were exposed to 5-50 ppm DEP for 6 hours. Regarding the metallothionein gene expressions, MT-1 and MT-2 were induced in the DEP-treated cell by using RT-PCR and real-time PCR. However, MT-3 which is known to be brain specific, and another isoform MT-4 were not expressed in cadmium-treated groups as well as control group. Heavy metal of DEP was also analyzed and Zn was found as the major component of heavy metals in DEP used in this study.

• Journal of Applied Biological Chemistry
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• v.43 no.1
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• pp.59-61
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• 2000

The cytotoxic activities of the methanol extracts of 44 plant species in 31 families against five human solid A549 (lung), SK-OV-2 (ovarian), SK-MEL-2 (melanoma), XF-498 (central nervous system), and HCT-15 (colon) tumor cell lines were examined using the sulforhodamine B (SRB) assay. Responses varied with both cell line and plant species used. Potent cytotoxic activities ($ED_{50}$, <$40{\mu}g/ml$) against all model tumor cell lines were produced from the extracts of Rhus chinensis gall (Galla rhois), Betula platyphylla var. japonica bark, Inula helenium root, Cinnamomum cassia bark, Cinnamomum sieboldii root bark, Lysimachia davurica whole plant, and Evodia rutaecarpa fruit. These plants may be useful for developing new types of naturally occurring anti-tumor agents.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.1
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• pp.77-84
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• 2003

Cancer, which is expressed in various forms, is one of the leading causes of human death, Soamsan (SAS) is composed of ten medicinal herb, the prescription was made according to the principles of Oriental traditional medicine based on the concept of synergic effects and interaction of among the components. SAS has been used for the cancer therapy, but the mechanism of it's effect is not well known. In the present study, the cytotoxic effect of the SAS water extract on cancer cell lines was investigated by the method of MTT in A549 cell lines and the anti-angiogenic effect was shown in the assay of chorioallantoic membrane (CAM) and in the cornea of rat administerd orally with SAS water extraction. The viability of A549 cell lines was not affected by the whole extract of SAS but the n-Hexan fraction of SAS water extract showed strong cytotoxicity which was not seemed to be done by the apoptotic mechanism. SAS water extract showed inhibition effects of angiogenesis induced in the cornea of rat and CAM assay. As the above results, it is suggested that SAS can be a candidate for new prescription for cancer therapy.

• The Journal of Internal Korean Medicine
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• v.18 no.1
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• pp.175-190
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• 1997

In order to investigate the effects of Gamihagochosan Extract(加味夏枯草散抽出液) on antitumor effects after human cell lines (A549, hep3B, Caki-1, Ehrlich) transplantation into the peritoneal cavity or right groin in mice induced by RPMI1640 and GIBCO etc., the extracts of its herbal medicines were orally administered for 10 or 12 days. Experimental studies were performed for measurement of antitumor effect of Mitomycin C(MMC) and lysosomal enzyme's activities using colony forming efficiency, SRB assay which were regarded as a valuable method for the measurement of antitumor effects of unknown compound on tumor cell lines. The results obtained in this studies were as follows : 1. The change of colony-forming efficiency and SRB assay of Caki-1 cells, hep3B and A549 Cells after exposure to the extract of Gamihagochosan extract depressed the growth of tumor cells by concentration of Garnihagochosan. 2. Antitumor activity of the ethanol extract from Gamihggochosan extract and MMC on ascites form of Ehrlich carcinoma in mice is slightly improved. Especially the mean of survival times in the group of 200mg/kg and MMC 0.1mg/kg is improved over 34.9%. 3. When Gamihggochosan extract and MMC are administered together, the weight of tumor is more decreased than MMC alone. 4. The lysosomal enzyme's activities of the Gamihagochosan extract and MMC are more significantly improved than MMC alone. According to the above result, it could be suggested that Gamihagochosan extract has indirect antitumor effect by the increase of MMC uptake.