• Tuberculosis and Respiratory Diseases
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• v.56 no.6
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• pp.638-645
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• 2004

Background : Uteroglobin is a protein produced by the normal bronchial epithelium and its expression level is lower in non-small cell lung cancer tissues and cell lines. It mainly functions as an anti-inflammatory, and when it is overexpressed in cancer cells, the neoplastic phenotype is antagonized. cPLA2 and COX-2, which are also associated with inflammation, were reported to be related to cancer. The relationship between cPLA2, COX-2 and uteroglobin is unclear. The relationship between uteroglobin and ERK, which is related to cell growth, is also not unclear. This study investigated the changes in the cPLA2 and COX-2 expression levels and the ERK activities after the overexpression of uteroglobin in non-small cell lung cancer cell lines. Methods : The A549 and NCI-H460 cell lines were infected by adenovirus-null and adenovirusuteroglobin. The cChange in the cPLA2, COX-2 expression level and ERK activity after uteroglobin overexpression was measured by Western blot. The change in MMP activity was measured by zymography. Results : Western blot revealed decreased expression levels of cPLA2, and COX-2, and increased pERK levels in nonsmall cell lung cancer cells after uteroglobin overexpression. Zymography revealed no changes in the MMP-2 activity and lower MMP-9 activity. U0126, which is a specific inhibitor of ERK-activating kinase MEK-1/-2, prevented the decrease in the MMP-9 activity Conclusions : A decrease in cPLA2 expression, COX-2 expression, MMP-9 activity and a increase in ERK activity may be related to the anticancer effects of uteroglobin in nonsmall cell lung cancer cells.

• Tuberculosis and Respiratory Diseases
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• v.52 no.5
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• pp.463-474
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• 2002

Background : This study was designed to examine how glutathione, one of the nucleophilic sulfur compounds, effects the cisplatin cellular toxicity in the non-small cell lung cancer cell lines and normal lung epithelial cell line. Materials and Methods : Three cultured cell lines, the lung adenocarcinoma cell(NCL-H23), the lung squamous carcinoma cell(SK-MES-1) and the normal lung epithelial cell(L-132) line were exposed to various concentrations of cisplatin with or without glutathione. The relative viability was estimated as a means of measuring the cisplatin cellular toxicity using the MTT method. Results : In NCI-23, the response to cisplatin was sensitive but glutathione markedly increased the relative survival of the tumor cells by removing the antitumor effect of cisplatin. In both SK-MES-1 and L-132, the responses to cisplatin were less sensitive, and the chemoprotective effect of glutathione compared to and equal cisplatin dose was significantly higher in L-132 than in SK-MES-1(p<0.05). Conclusion : The protective effectes of of glutathione on cisplatin-induced cellular toxicity is more significant in normal lung epithelial cells than in squamous carcinoma cells.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5883-5887
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• 2015

Despite recent advances in therapeutic strategies for lung cancer, mortality still is increasing. In the present study, we investigated the anti-cancer effects of KMU-193, 2-(4-Ethoxy-phenyl)-N-{5-[2-fluoro-4-(4-methylpiperazine-1-carbonyl)-phenylamino]-1H-indazol-3-yl}-acetamide in a human non-small cell lung cancer cell line A549. KMU-193 strongly inhibited the proliferation of A549 cells, but it did not have anti-proliferative effect in other types of cancer cell lines. KMU-193 further induced apoptosis in association with activation of caspase-3 and cleavage of PLC-${\gamma}1$. However, KMU-193 had no apoptotic effect in untransformed cells such as TMCK-1 and BEAS-2B. Interestingly, pretreatment with z-VAD-fmk, a pan-caspase inhibitor, strongly abrogated KMU-193-induced apoptosis. KMU-193 treatment enhanced the expression levels of p53 and PUMA. Importantly, p53 siRNA transfection attenuated KMU-193-induced apoptosis. Collectively, these results for the first time demonstrate that KMU-193 has strong apoptotic effects on A549 cells and these are largely mediated through caspase-3- and p53-dependent pathways.

• Nutrition Research and Practice
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• v.9 no.1
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• pp.11-16
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• 2015

BACKGROUND/OBJECTIVES: Perilla frutescens Britton leaves are a commonly consumed vegetable in different Asian countries including Korea. Cancer is a major cause of human death worldwide. The aim of the current study was to investigate the inhibitory effects of ethanol extract of perilla leaf (PLE) against important characteristics of cancer cells, including unrestricted growth, resisted apoptosis, and activated metastasis, using human cancer cells. MATERIALS/METHODS: Two human cancer cell lines were used in this study, HCT116 colorectal carcinoma cells and H1299 non-small cell lung carcinoma cells. Assays using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide were performed for measurement of cell growth. Soft agar and wound healing assays were performed to determine colony formation and cell migration, respectively. Nuclear staining and cell cycle analysis were performed for assessment of apoptosis. Fibronectin-coated plates were used to determine cell adhesion. RESULTS: Treatment of HCT116 and H1299 cells with PLE resulted in dose-dependent inhibition of growth by 52-92% (at the concentrations of 87.5, 175, and $350{\mu}g/ml$) and completely abolished the colony formation in soft agar (at the concentration of $350{\mu}g/ml$). Treatment with PLE at the $350{\mu}g/ml$ concentration resulted in change of the nucleus morphology and significantly increased sub-G1 cell population in both cells, indicating its apoptosis-inducing activity. PLE at the concentration range of 87.5 to $350{\mu}g/ml$ was also effective in inhibiting the migration of H1299 cells (by 52-58%) and adhesion of both HCT116 and H1299 cells (by 25-46%). CONCLUSIONS: These results indicate that PLE exerts anti-cancer activities against colon and lung cancers in vitro. Further studies are needed in order to determine whether similar effects are reproduced in vivo.

• Natural Product Sciences
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• v.25 no.4
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• pp.311-316
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• 2019

Artocarpus heterophyllus has been used as traditional medicine. This plant is one of the sources of flavonoid. Flavonoid compounds possessed a wide range of biological properties including anticancer. This study was performed to investigate the cytotoxic effect of flavonoids from A. heterophyllus on H460 and MCF-7 cell lines. The interaction of flavonoids and cisplatin against tested cancer cells was also evaluated. MTT assay was used to determine the cytotoxic effect of flavonoid. Isobologram analysis was selected to evaluate the synergistic effect between flavonoid and cisplatin, their interaction was then confirmed using AO/PI staining method. Amongst of flavonoid compounds, artocarpin exhibited strong cytotoxic effect on both MCF-7 and H460 cell lines with IC₅₀ values of 12.53 ㎍/mL (28.73 μM) and 9.77 ㎍/mL (22.40 μM), respectively. This compound enhanced anticancer activity of cisplatin against H460 and MCF-7. The combination produced a synergistic effect on H460 and MCF-7 cell lines with a combination index (CI) values of 0.2 and 0.18, respectively. The AO/PI stained demonstrated that the combination of artocarpin and cisplatin caused morphological changes that indicated apoptosis. Moreover, artocarpanone also significantly increased cytotoxic effect of cisplatin compared to its single concentration with CI below than 1. This result suggested the potency of flavonoid named artocarpin to enhance the anticancer activity of cisplatin on H460 and MCF-7 cell lines.

• Korean Journal of Acupuncture
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• v.41 no.1
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• pp.7-15
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• 2024

Objectives : This study aimed to predict the effectiveness and potential of Schizonepeta tenuifolia as an anticancer treatment for non-small cell lung cancer through network-based pharmacology and cellular experiment. Methods : To identify the major bioactive compounds in Schizonepeta tenuifolia, we used the Traditional Chinese Medicine Systems. The target genes for the cancer treatment were selected using the UniProt database and the networked using Cytoscape. We performed functional enrichment analysis based on the Gene Ontology Biological Process and Kyoto Encyclopedia of Genes and Genomes Pathways to predict the mechanisms. To investigate the effect of Schizonepeta tenuifolia on lung cancer cell growth, we treated A549 cells, a lung cancer cell line, with different concentrations of the drug and used the MTT assay for cell viability. Results : Research has shown that the most effective mechanism of active compounds from Schizonepeta tenuifolia is through the pathway of cancer. The results of the network pharmacology analysis indicate that Schizonepeta tenuifolia has potential medicinal value as an adjuvant in anticancer treatment. The concentration-dependent inhibition of cell viability was observed on A549 cells. Furthermore, synergistic anticancer activity with Doxorubicin was also observed. Conclusions : Through a network pharmacological approach, Schizonepeta tenuifolia was predicted to have potential as an anticancer agent, and its efficacy was experimentally demonstrated using A549 cells. These findings suggest that Schizonepeta tenuifolia is a promising candidate for future research.

• Molecules and Cells
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• v.41 no.6
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• pp.591-602
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• 2018

Gastric cancer is the fifth most common type of malignancy worldwide, and the survival rate of patients with advanced-stage gastric cancer is low, even after receiving chemotherapy. Here, we validated neurotensin receptor 1 (NTSR1) as a potential therapeutic target in gastric cancer. We compared NTSR1 expression levels in sixty different gastric cancer-tissue samples and cells, as well as in other cancer cells (lung, breast, pancreatic, and colon), by assessing NTSR1 expression via semi-quantitative real-time reverse transcription polymerase chain reaction, immunocytochemistry and western blot. Following neurotensin (NT) treatment, we analyzed the expression and activity of matrix metalloproteinase-9 (MMP-9) and further determined the effects on cell migration and invasion via wound-healing and transwell assays. Our results revealed that NTSR1 mRNA levels were higher in gastric cancer tissues than non-cancerous tissues. Both of NTSR1 mRNA levels and expression were higher in gastric cancer cell lines relative to levels observed in other cancer-cell lines. Moreover, NT treatment induced MMP-9 expression and activity in all cancer cell lines, which was significantly decreased following treatment with the NTSR1 antagonist SR48692 or small-interfering RNA targeting NTSR1. Furthermore, NT-mediated metastases was confirmed by observing epithelial-mesenchymal transition markers SNAIL and E-cadherin in gastric cancer cells. NT-mediated invasion and migration of gastric cancer cells were reduced by NTSR1 depletion through the Erk signaling. These findings strongly suggested that NTR1 constitutes a potential therapeutic target for the inhibition of gastric cancer invasion and metastasis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.3
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• pp.722-728
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• 2005

The DNA topoismerase I inhibitor ${\beta}-lapachone$, the product of a lapacho tree (Tabebuia avellanedae) from South America, activates a novel apoptotic response in a number of cell lines. In the present report, we investigated the effects of ${\beta}-lapachone$ on the growth of human lung in human non-small-cell-lung-cancer A549 cells. Upon treatment with ${\beta}-lapachone$, a concentration-dependent inhibition of cell viability and cell proliferation was observed as measured by hemocytometer counts and MTT assay. The ${\beta}-lapachone-treated$ cells developed many of the hallmark features of apoptosis, including membrane shrinking, condensation of chromatin and DNA fragmentation. These apoptotic effects of ${\beta}-lapachone$ in A549 cells were associated with a marked induction of pro-apoptotic Bax expression, however the levels of anti-apoptotic Bcl-2 expression were decreased in a dose-dependent manner. Accordingly, elevated amount of cyclin-dependent kinase inhibitor p21 expression accompanied by up-regulation of tumor suppressor p53 was observed. By RT-PCR analyses, decrease in gene expression level of telomerase reverse transcriptase and telomeric repeat binding factor were also observed. Thus, these findings suggest that ${\beta}-lapachone$ may be a potential anti-cancer therapeutics for the control of human lung cancer cell model.

• Journal of Life Science
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• v.29 no.12
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• pp.1305-1313
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• 2019

Licochalcone (LC), isolated from the roots of Glycyrrhiza inflata has multiple pharmacological effects including anti-inflammatory and anti-tumor activities. To date, Licochalcone C (LCC) has induced apoptosis and inhibited cell proliferation in oral and bladder cancer cells, but lung cancer has not yet been studied. In addition, no study reported LCC-induced autophagy in cancer until now. The present study was designed to investigate the effect of LCC on gefitinib-sensitive and -resistant lung cancer cells and elucidate the mechanism of its action. The 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay data showed that LCC significantly inhibited cell viability in non-small cell lung cancer (NSCLC) HCC827 (gefitinib-sensitive) and HCC827GR (gefitinib-resistant) cell lines. Interestingly, Annexin V/7-aminoactinomycin D double staining and cell cycle analysis showed an apoptosis rate within about 20% at the highest concentration of LCC. LCC induced G2/M arrest by reducing the expression of the cell cycle G2/M related proteins cyclin B1 and cdc2 in NSCLC cell lines. Treatment of LCC also induced autophagy by increasing the expression of the autophagy marker protein microtubule-associated protein 1 light chain 3 (LC3) and the protein autophagy-related gene 5 involved in the autophagy process. In addition, LCC increased the production of reactive oxygen species (ROS), and the cell viability was partially restored by treatment with the ROS inhibitor N-acetyl-L-cysteine. In western blotting analysis, the expression of cdc2 was increased and LC3 was decreased by the simultaneous treatment of NAC and LCC. These results indicate that LCC may contribute to anti-tumor effects by inducing ROS-dependent G2/M arrest and autophagy in NSCLC. In conclusion, LCC treatment may be useful as a potential therapeutic agent against NSCLC.

• Tuberculosis and Respiratory Diseases
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• v.56 no.4
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• pp.381-392
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• 2004

Arsenic trioxide($As_2O_3$) was introduced into the treatment of refractory or relapsed acute promyelocytic Ieukemia. Some investigators have reported that arsenic trioxide had induced apoptosis in a variety of solid human tumor cell lines, including non-small cell lung cancer. Non-steroidal anti-inflammatory drugs(NSAIDs) are powerful chemopreventive agents for gastrointestinal cancers and the growth of established tumors are reduced by inducing apoptosis. It's also reported that NSAIDs enhanced tumor response to chemotherapeutic drugs or radiation. In this study, we aimed to determine whether combination of arsenic trioxide with sulindac augmented its apoptotic potential in NCI-H157 human lung cancer cells. The human lung cancer cell line NCI-H157 was treated with arsenic trioxide and sulindac. Cell viability was measured by the MTT assay. Apoptosis was measured by nuclear staining and flow cytometric analysis. The catalytic activity of the caspase families were measured by the fluorogenic cleavage of biosubstrates. The western blotting were also performed to define the mechanical basis of apoptosis. Combination treatment of arsenic trioxide and sulindac decreased the viability of NCI-H157 human lung cancer cells in a dose-dependent manner. The catalytic activity of caspase-3, 8 and 9 proteases were increased after combination treatment. Consistently PARP was cleaved from 116kDa to 85kDa fragments, and the expression of ICAD was decreased by time-dependent manner. Also combination treatment increased the expression of Fas and Fas/L. Combination therapy of arsenic trioxide with sulindac augments cell death and induces apoptosis via the activation of caspase cascade in NCI-H157 human lung carcinoma cells.