• Journal of Nutrition and Health
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• v.35 no.1
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• pp.53-59
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• 2002

Green tea has been recognized as a favorite beverage for centuries in Easter and Westers cultures. Recently, anti-tumor effects of green tea constituents have received increasing attention. However, the mechanism of catechin-mediated cytotoxicity against tumor cells remains to be elusive. To elucidate the mechanical insights of anti-tumor effects, (-)epigallocatechin-gallate(EGCG) of catechin was applied to human lung cancer A549 cells. (-)EGCG induced the death of A549 cells, which was revealed as apoptosis in DNA fragmentation assay. (-)EGCG induced the activation of caspase family cysteine proteases including capase-3, -8 and -9 proteases in A549 cells. Furthermore, (-)EGCG increased the phosphotransferase activity of c-Jun N-terminal kinase 1JNK 1), which further induced tole transcriptional activation of activating protein-1(AP-1) in A549 cells. We suggest that (-)EGCG-induced apotosis of A549 cells is mediated by signaling pathway involving caspase family cysteine protease, JNK1 and transcription factor, AP-1.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.11
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• pp.4893-4898
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• 2016

Objective: To investigate the impact of a Croton tiglium extract on cellular proliferation and apoptosis in a non-small cell lung cancer cell line (A549) in vitro. Methods: A Croton tiglium seed methanol extract was prepare and assessed for effects on A549 cells regarding cellular proliferation, apoptotic rates, and expression of apoptosis related genes and proteins using real-time PCR and immunofluorescence. Results: The tested Croton tiglium extract inhibited A549 cell proliferation in a dose- and time-dependent manner, with significant elevation of apoptotic indexes at various concentrations after 24 h. In addition, rates in both early and late stages were higher in treated than untreated groups, the $100{\mu}g/ml$ dose causing the highest levels of apoptosis. RT-PCR showed that A549 cells treated with $100{\mu}g/ml$ Croton tiglium extract for 24 h has markedly higher Bax mRNA expression levels and obviously lower Bcl-2 expression levels than controls, equivalent results being observed for proteins by immunofluorescence. However, the mRNA expression levels of Fas and caspase-8 were not significantly altered. Conclusion: A Croton tiglium extract can inhibit proliferation of A549 cells and promote apoptosis though Bax/Bcl-2 pathways.

• Radiation Oncology Journal
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• v.7 no.1
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• pp.1-13
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• 1989

Effects of ionizing radiation alone and combined with chemotherapy on tumor growth and it's clonal specificity monitored by changes in distribution of chromosome number were studies in A549 ceil line originated from human adenocarcinoma of the lung. Radiation (300 rad, 600 rad and 900 rad) were delivered with or without 5-FU. Forty eight hours later, 57.5% of growth inhibition of cell w8s seen in cells treated with 5-FU concentration of $0.4{\mu}g/ml$ for 24hr exposure. Cell survival curves after radiation with and without 5-FU were made. Chromosomal analysis of cells in metaphase in control, and in cells treated with 300 rad of radiation, or $0.4{\mu}g/ml$ of 5-FU treatment, and combined treatment of both were done to examine the changes in ploidy and number of chromosome. Radiation combined with S-FU enhanced growth inhibition of A549 cells. However, no evidence of synergegic effects in growth. inhibition was observed in the cells treated with the combination therapy. Pattern of chromosomal distribution of survived cells were shifted from hyperploidy to hypoploidy by single dose of radiation (300 rad). As radiation dose increased a large number of hypoploidy cells were observed. Following treatment of cells with 5-FU, chomosomal distribution of survived cells were also shifted to hypodiploidy which were seen in cells treated with radiation, The ceil treated with 5-FU and fellowed by radiation within 24 hrs had cell with increased number of hypodiploidy cells. Almost same type of chromosomal changes were reproduced in cells treated with combined treatment with radiation and 5-FU. Minor differences were that cells with fewer number of chromosome were more frequent in cells treated with combined therapy. Further increase in cells of hypoploidy (93%) having 1-10 chromosome were induced by additional radiation. Therefore, the enhanced therapeutic effect of 5-FU combined with radiation of A549 cells appeared to be additive rather than synergistic.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.10
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• pp.4755-4759
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• 2016

Introduction: Lung cancer is one of the most common cancers worldwide. In certain countries such as United States of America, it is the leading cause of related cancer mortality among both men and women. Natural products play an important role in overcoming the limitations of chemotherapy and radiotherapy. Objectives: In this study, we investigated the antiproliferative and apoptotic activities of Kanahia laniflora methanolic extract against human non-small cell lung cancer cells (A549). Methods: Sulforhodamine B colorimetric assays were used to determine the inhibitory effects of a leaf methanolic extract against A549 cells. Results: The extract showed strong cytotoxic activity against A549 cells with an $IC_{50}$ value of $0.13{\mu}g/ml$ compared to $0.21{\mu}g/ml$ for doxorubicin. The extract also significantly increased the percentage of apoptotic cells to 49.7% as compared to 1.4% and 47.4% for control and doxorubicin respectively. Conclusion: These results showed, for the first time, that a methanolic extract of Kanahia laniflora leaves can inhibit the proliferation of human non-small cell lung cancer cells (A549). Further attention to its potential as a new effective anticancer agent is warranted.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.4
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• pp.1019-1030
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• 2003

Platycodi Radix, the root of Platycodon grandiflorum, commonly known as Doraji, is used as a traditional oriental medicine. Extracts from the roots of P. grandiflorum have been reported to have wide ranging health benefits. In the present study, we investigated the effects of an aqueous extract from the roots of P. grandiflorum (AEPG) on the growth of human lung carcinoma A549 cells. Results obtained are as fellow; AEPG treatment resulted in the inhibition of the cell viability of A549 cells in a concentration-dependent manner. Upon treatment with AEPG, A549 cells developed many of the hallmark features of apoptosis, including condensation of chromatin. Flow cytometry analysis confirmed that AEPG increased populations of apoptotic-sub G1 phase. Western blot and RT-PCR analyses indicated that the expressions of Bcl-2 was down-regulated but Bax was up-regulated in AEPG-treated A549 cells. AEPG-induced apoptotis of A549 cells was associated with rroteolytic cleavage and activation of caspase-3, release of cytochrome c from mitochondria into cytosol and down-regulation of Akt and phospho-Akt proteins in a dose-dependent manner. Induction of apoptosis by AEPG treatment was associated with inhibition and/or degradation of apoptotic target proteins such as poly(ADP-ribose) polymerase, β-catenin and phospholipase C-γ 1. AEPG treatment inhibited the levels of cyclooxygenases protein of A549 cells, which was associated with the inhibition of prostaglandin E2 accumulation in a concentration-dependent fashion. Taken together, these findings suggest that P. grandiflorum has strong potential for development as an agent for prevention against human lung cancer.

• Parasites, Hosts and Diseases
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• v.31 no.3
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• pp.215-222
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• 1993

In order to establish a useful cell culture system for T gondii we compared the degree of proliferation of T gondii tachyzoites among 8 different cell lines: 2 kinds of normal animal cells (MDCK-canine kidney cells; Vero-monkey kidney cells) and 6 kinds of human tumor cells (A 549, PC 14-lung cancer cells; SNU 1, SNU 16. Mlm 45-stomach cancer cells; HL-60-promyelocytic leukemia cells), through morphological observation and 3H-uracil uptake assay. The degree of susceptibility to infection with T gondii tachyzoites was highest in A 549 and PC 14 cells, medium in Vero, HL-60, MDCK and SNU 1, and lowest in SNU 16 and MBm 45 cells. The kinetics of T gondii multiplication during the post-Infection 60 hours were higllly dependent upon the dose of tachyzoites administered and the duration among the 8 tested fur the growth and multiplication of T gondii in vitro.

• Journal of Physiology & Pathology in Korean Medicine
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• v.30 no.3
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• pp.150-156
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• 2016

Extract of Broussometia kazinoki Rhizodermatis has been traditionally used for geopoong, diuresis, hwalhyeol. In the present study, the apoptotic effect of methanol extract of Broussometia kazinoki (MBK) were investigated. Cell viability of A549 cells was measured by MTT assay. Apoptosis-related protein and MAPK protein levels were measured by Western blot. Chromatin condensation of A549 cells was stained with DAPI. MBK inhibited cell proliferation of A549 cell. Based on DAPI staining, MBK-treated cells manifested nuclear shrinkage, condensation and fragmentation. Treatment of A549 cells with MBK resulted in activation of the caspase-3, -8, -9 and cleavage of poly ADP-ribose polymerase (PARP). In the upstream, MBK increased the expressions Bax and Bak, decreased the expression of Bcl-2, and augmented the Bax/Bcl-2 ratio. MBK-induced apoptosis was accompanied by sustained phosphorylation of JNK, p38 MAPK and apoptosis signal-regulating kinase (ASK)-1. These results suggest that MBK induced apoptosis in A549 cells through Bcl-2 family protein-mediated mitochondria/caspase-3 dependent pathway. In addition, MBK increased the activation of ASK-1, which are critical upsteam signals for JNK/p38 MAPK activation in A549 cancer cells.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.5
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• pp.465-474
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• 2017

The aim of this study was to determine the raising anticancer effects of resveratrol (Res) on paclitaxel (PA) in non-small cell lung cancer (NSCLC) cell line A549. The $10{\mu}g/ml$ of Res had no effect on human fetal lung fibroblast MRC-5 cells or on A549 cancer cells and the 5 or $10{\mu}g/ml$ of PA also had no effect on MRC-5 normal cells. PA-L ($5{\mu}g/ml$) and PA-H ($10{\mu}g/ml$) had the growth inhibitory effects in NSCLC cell line A549, and Res increased these growth inhibitory effects. By flow cytometry experiment, after Res ($5{\mu}g/ml$)+PA-H ($10{\mu}g/ml$) treatment, the A549 cells showed the most apoptosic cells compared to other group treatments, and after additional treatment with Res, the apoptosic cells of both two PA concentrations were raised. Res+PA could reduce the mRNA and protein expressions of COX-2, and Res+PA could reduce the COX-2 related genes of VEGF, MMP-1, MMP-2, MMP-9, $NF-{\kappa}B$, Bcl-2, BclxL, procollagen I, collagen I, collagen III and CTGF, $TNF-{\alpha}$, $IL-1{\beta}$, iNOS and raise the TIMP-1, TIMP-2, TIMP-3, $I{\kappa}B-{\alpha}$, p53, p21, caspase-3, caspase-8, caspase-9, Bax genes compared to the control cells and the PA treated cells. From these results, it can be suggested that Res could raise the anticancer effects of PA in A549 cells, thus Res might be used as a good sensitizing agent for PA.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5725-5730
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• 2013

Cancer patients often suffer from local tumor recurrence after radiation therapy. Cell cycling, an intricate sequence of events which guarantees high genomic fidelity, has been suggested to affect DNA damage responses and eventual radioresistant characteristics of cancer cells. Here, we established a radioresistant lung cancer cell line, A549R, by exposing the parental A549 cells to repeated ${\gamma}$-ray irradiation with a total dose of 60 Gy. The radiosensitivity of A549 and A549R was confirmed using colony formation assays. We then focused on examination of the cell cycle distribution between A549 and A549R and found that the proportion of cells in the radioresistant S phase increased, whereas that in the radiosensitive G1 phase decreased. When A549 and A549R cells were exposed to 4 Gy irradiation the total differences in cell cycle redistribution suggested that G2-M cell cycle arrest plays a predominant role in mediating radioresistance. In order to further explore the possible mechanisms behind the cell cycle related radioresistance, we examined the expression of Cdc25 proteins which orchestrate cell cycle transitions. The results showed that expression of Cdc25c increased accompanied by the decrease of Cdc25a and we proposed that the quantity of Cdc25c, rather than activated Cdc25c or Cdc25a, determines the radioresistance of cells.

• Journal of Society of Preventive Korean Medicine
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• v.17 no.2
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• pp.169-178
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• 2013

Objectives : Many cancers acquired resistance to chemotherapy, thus limiting its anticancer efficacy. It is known that Glutathione (GSH) is related to the development of drug resistance. The expression of GSH synthesizing glutamylcysteine ligase (GCL) was controlled by nuclear factor-E2-related factor(Nrf2). Previous studies showed that pharmacological depletion of GSH results in ROS increase, apoptotic response, and sensitization to oxidizing stimuli. In the current study, we examined Saussurea Lappa (SL) have the inhibitory effect on Nrf2 activity using human lung cancer A549 cells overexpressing Nrf2. Methods : Cell viability of A549 cells on SL treatment was determined by MTT assay. To detect the apeptosis in SL-treated A549 cells, sub-G1 population was measured by flow cytometry analysis (FACS). The level ROS was determined by FACS and fluorescence microscopy. To investigate whether SL have effect the suppression on Nrf2, we performed western blotting analysis. The GSH content was measured since GSH plays an important role in response to oxidative stress and was regulated by Nrf2. Results : A549 cells treated with an SL extract showed a substantial decrease in cell viability, along with a concomitant increase in apoptosis compared to untreated cells. Treatment of the SL extract led to increased Reactive oxygen species (ROS) production and a suppression of Nrf2. In addition, the antioxidant NAC attenuated SL-induced ROS generation, Nrf2 inhibition, and apoptosis. Taken together, these data show that the SL extract induced the production of ROS, and the inhibition of Nrf2, consequently resulting in A549 cell death. Conclusions : These results suggest that SL might be an effective agent to enhance anticancer drug sensitivity via Nrf2 inhibition.