• Proceedings of the Plant Resources Society of Korea Conference
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• 2019.04a
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• pp.93-93
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• 2019

In this study, we evaluated the anti-cancer activity and potential molecular mechanism of 70% ethanol extracts of branches from Taxillus yadoriki parasitic to Neolitsea sericea (TN-NS-B) against human lung cancer cells, A549. TY-NS-B dose-dependently suppressed the growth of A549 cells. TY-NS-B decreased ${\beta}$-catenin protein level, but not mRNA level in A549 cells. The downregulation of ${\beta}$-catenin protein level by TY-NS-B was attenuated in the presence of MG132. Although TY-NS-B phosphorylated ${\beta}$-catenin protein, the inhibition of $GSK3{\beta}$ by LiCl did not blocked the reduction of ${\beta}$-catenin by TY-NS-B. In addition, TY-NS-B decreased ${\beta}$-catenin protein in A549 cells transfected with Flag-tagged wild type ${\beta}$-catenin or Flag-tagged S33/S37/T41 mutant ${\beta}$-catenin construct. Our results suggested that TN-NS-B may downregulate ${\beta}$-catenin protein level independent on GSK3${\beta}$-induced ${\beta}$-catenin phosphorylation. Based on these findings, TY-NS-B may be a potential candidate for the development of chemopreventive or therapeutic agents for human lung cancer.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2019.04a
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• pp.92-92
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• 2019

In this study, we evaluated the effect of branch (STB) and leave (STL) extracts from Sageretia thea on ${\beta}$-catenin level in human colorecal cancer cells, SW480 and lung cancer cells, A549. STB and STL dose-dependently suppressed the growth of SW480 and A549 cells. STB and STL decreased ${\beta}$-catenin level in both protein and mRNA level. MG132 decreased the downregulation of ${\beta}$-catenin protein level induced by STB and STL. However, the inhibition of $GSK3{\beta}$ by LiCl or ROS scavenging by NAC did not block the reduction of ${\beta}$-catenin protein by STB and STL. Our results suggested that STB and STL may downregulate ${\beta}$-catenin protein level independent on $GSK3{\beta}$ and ROS. Based on these findings, STB and STL may be a potential candidate for the development of chemopreventive or therapeutic agents for human colorectal cancer and lung cancer.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.2
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• pp.131-141
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• 2023

Compelling evidence has demonstrated the critical role of circular RNAs (circRNAs) during lung adenocarcinoma (LUAD) progression. Herein, we explored a novel circRNA, circ_0129047, and detailed its mechanism of action. The expression of circ 0129047, microRNA-665 (miR-665), and protein tyrosine phosphatase receptor type B (PTPRB) in LUAD tissues and cells was determined using reverse transcription quantitative polymerase chain reaction and Western blotting. Cell Counting Kit8 and colony formation assays were conducted to detect LUAD cell proliferation, and western blotting was performed to quantify apoptosis-related proteins (Bcl2 and Bax). Luciferase reporter and RNA immunoprecipitation assays were used to validate the predicted interaction between miR-665 and circ_0129047 or PTPRB. A xenograft assay was used for the in vivo experiments. Circ_0129047 and PTPRB were downregulated in LUAD tissues and cells, whereas miR-665 expression was upregulated. Overexpression of circ_0129047 suppresses LUAD growth in vivo and in vitro. Circ_0129047 is the target of miR-665, and the miR-665 mimic ablated the antiproliferative and pro-apoptotic phenotypes of LUAD cells by circ_0129047 augmentation. MiR-665 targets the 3'UTR of PTPRB and downregulates PTPRB expression. PTPRB overexpression offsets the pro-proliferative potential of miR-665 in LUAD cells. Circ_0129047 sequestered miR-665 and upregulated PTPRB expression, thereby reducing LUAD progression, suggesting a promising approach for preventing LUAD.

• Molecules and Cells
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• v.25 no.2
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• pp.224-230
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• 2008

Ceramides are well-known second messengers that induce apoptosis in various kinds of cancer cells, and their effects are closely related to radiation sensitivity. Phytoceramides, the yeast counterparts of the mammalian ceramides, are also reported to induce apoptosis. We investigated the effect of a novel ceramide derivative, N-acetylphytosphingosine (NAPS), on the radiosensitivity of NCI-H460 human lung carcinoma cells and its differential cytotoxicity in tumor and normal cells. The combination of NAPS with radiation significantly increased clonogenic cell death and caspase-dependent apoptosis. The combined treatment greatly increased Bax expression and Bid cleavage, but not Bcl-2 expression. However, there was no effect on radiosensitivity and apoptosis in BEAS2B cells, which derive from normal human bronchial epithelium. Cell proliferation and DNA synthesis were significantly inhibited by NAPS in both NCI-H460 and BEAS2B cells, but only the BEAS2B cells recovered by 48h after removal of the NAPS. Furthermore, the NCI-H460 cells underwent more DNA fragmentation than the BEAS2B cells in response to NAPS. Our results indicate that NAPS may be a potential radiosensitizing agent with differential effects on tumor vs. normal cells.

• KSBB Journal
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• v.11 no.2
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• pp.254-261
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• 1996

Attenuated varicella-zoster virus (VZV) was propagated in human lung fibroblast (HLF) cells Among media tested in this work, DMEM was the best medium for the growth of HLF cells. Because HLF was a normal finite cell line, cell growth late was dependent on the age of HLF cells. When the population doubling level (PDL) was higher than 46, apoptosis of HLF cells started and cell growth rate decreased. The optimum temperature for the cell growth and virus propagation in the T-flask culture was $37^{\circ}C$. In a microcarrier culture system in which Cytodex-3 was used for the VZV propagation in spinner vessels, the yield of plaque forming cells was lower than that in the T-flask culture. The relatively high shear environment near microcarriers was thought to cause the low yield of VZV in the microcarrier culture system.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2425-2430
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• 2015

Clinical resistance to chemotherapeutic agents is one of the major hindrances in the treatment of human cancers. EHZ2 is involved in drug resistance and is overexpressed in drug-resistant cancer cell lines. In this study, we investigated the effects of EHZ2 on cisplatin -resistance in A549/DDP and AGS/DDP cells. EHZ2 mRNA and protein were found to be significantly overexpressed in A549/DDP and AGS/DDP cells, compared to parental cells. EHZ2 siRNA successfully silenced EHZ2 mRNA and protein expression. Proliferation was inhibited and drug resistance to cisplatin was improved. Flow cytometry showed that silencing of EHZ2 arrested A549/DDP and AGS/DDP cells in the G0/G1 phase, increasing apoptosis, rh-123 fluorescence intensity and caspase-3/8 activities. Silencing of EHZ2 also significantly reduced the mRNA and protein expression levels of cyclin D1 and MDR1,while up-regulating p15, p21, p27 and miR-218 in A549/DPP cells. Furthermore, silencing of EHZ2 also significantly increased the expression level of tumor suppressor factor miR-218. We also found down-regulating EHZ2 expression increased methylation in A549/DDP and AGS/DDP cells. This study demonstrates that drug resistance can be effectively reversed in human cisplatin-resistant lung and gastric cancer cells through delivery of siRNAs targeting EHZ2.

• Journal of Microbiology and Biotechnology
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• v.20 no.2
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• pp.433-437
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• 2010

In the course of screening for novel modulators of cell cycle progression and apoptosis as anticancer drug candidates, we generated an analog of sangivamycin, MCS-C2, which was elucidated as 4-amino-6-bromo-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide. In the present study, we evaluated the molecular mechanisms of MCSC2-induced cell cycle arrest and apoptosis in A549 human lung cancer cells. To investigate the effects of MCS-C2 on cell cycle progression in A549 cells, we measured the DNA content of A549 cells treated with $5\;{\mu}M$ MCS-C2 using flow cytometry. The analysis revealed an appreciable $G_2$ phase arrest in treated cells. This event was associated with significant upregulation of p53 and $p21^{Cip1}$. In addition, the TUNEL assay was used to examine apoptotic induction in treated cells, and the effects of MCS-C2 on the expression of apoptosis-associated proteins were examined by Western blot. Apoptotic induction in MCS-C2-treated A549 cells was associated with cytochrome c release from mitochondria, which in turn resulted in the activation of caspase-9 and -3 and the cleavage of poly(ADP-ribose) polymerase (PARP). Based on these results, we conclude that MCS-C2 is a candidate therapeutic agent for the treatment of human lung cancer via upregulation and activation of p53.

• Archives of Pharmacal Research
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• v.21 no.5
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• pp.549-554
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• 1998

Tissue factor (TF), a principal initiator of the veertebrate coagulation cascade, is expressed in organ tissues, cells and blood. TF is konwn to be induced in endothelial cells, monocytes and macrophages by inflammatory stimuli and in many pathologic conditions. By using the modified method for in vido TF activity assay, we found that turpentine oil injection as an inflamatory stimulus also induced the TF activity in lung and brain tissues of rats. And the age-related increase in Tf activity was observed in healthy rat brain tissue.

• Nuclear Engineering and Technology
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• v.40 no.7
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• pp.539-550
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• 2008

Lung cancer is the most prevalent global cancer, ${\sim}90%$ of which is caused by cigarette smoking. The LNT hypothesis has been inappropriately applied to estimate lung cancer risk due to ionizing radiation. A threshold of ${\sim}1\;Gy$ for lung cancer has been observed in never smokers. Lung cancer risk among nuclear workers, radiologists and diagnostically exposed patients was typically reduced by ${\sim}40%$ following exposure to <100 mSv low LET radiation. The consistency and magnitude of reduced lung cancer in nuclear workers and occurrence of reduced lung cancer in exposed non-worker populations could not be explained by the HWE. Ecologic studies of indoor radon showed highly significant reductions in lung cancer risk. A similar reduction in lung cancer was seen in a recent well designed case-control study of indoor radon, indicating that exposure to radon at the EPA action level is associated with a decrease of ${\sim}60%$ in lung cancer. A cumulative whole-body dose of ${\sim}1\;Gy$ gamma rays is associated with a marked decrease in smoking-induced lung cancer in plutonium workers. Low dose, low LET radiation appears to increase apoptosis mediated removal of $\alpha$-particle and cigarette smoke transformed pulmonary cells before they can develop into lung cancer.

• Journal of Chest Surgery
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• v.43 no.5
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• pp.499-505
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• 2010

Background: There have been several reports using animal experiments that CD1-restricted T-cells have a key role in tumor immunity. To address this issue, we studied the expression of markers for CD1c+ myeloid dendritic cells (DCs) isolated from peripheral blood in the clinical setting. Material and Method: A total of 24 patients with radiologically suspected or histologically confirmed lung cancer who underwent pulmonary resection were enrolled in this study. The patients were divided according to histology findings into three groups: primary adenocarcinoma of lung (PACL), primary squamous cell carcinoma of lung (PSqCL) and benign lung disease (BLD). We obtained 20 mL of peripheral venous blood from patients using heparin-coated syringes. Using flow-cytometry after labeling with monoclonal antibodies, data acquisition and analysis were done. Result: The ratio of CD1c+CD19- dendritic cells to CD1c+ dendritic cells were not significantly different between the three groups. CD40 (p=0.171), CD86 (p=0.037) and HLA-DR (p=0.036) were less expressed in the PACL than the BLD group. Expression of CD40 (p=0.319), CD86 (p=0.036) and HLA-DR (p=0.085) were less expressed in the PACL than the PSqCL group, but the differences were only significant for CD86. Expression of co-stimulatory markers was not different between the PSqCL and BLD groups. Expression of markers for activated DCs were dramatically lower in the PACL group than in groups with other histology (CD40 (p=0.005), CD86 (p=0.013) HLA-DR (p=0.004). Conclusion: These results suggest the possibility that CD1c+ myeloid DCs participate in control of the tumor immunity system and that low expression of markers results in lack of an immune response triggered by dendritic cells in adenocarcinoma of the lung.