• Bulletin of the Korean Chemical Society
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• v.34 no.4
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• pp.1293-1295
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• 2013

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.5
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• pp.1204-1212
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• 2005

Lung cancer is one of the common malignant tumors in the world. It occurs more increasingly due to the serious air pollution, heavy smoking, expoure to ionized radiation, pollution with heavy metal, and owing to well advanced diagnostic skill, etc. Also lung cancer has the limitation of medical care because metastasis is already shown up in more than half cases when it is first detected through medical examination. Although it is treated with chemoradiation, the rate of deaths from lung cancer is high as well, because blood has a lot of toxicity which give side effects. So it has a low rate of cure. So, the ways of various treatment is being researched to raise the rate of care and decrease the side effects recently, and one of the results is inducing apoptosis which makes use of molecularbiologic diagnosis of lung cancer's cell and using oriental medicine drugs. The purpose of this study is whether apoptosis would happen on the human lung carcinoma cell by treated with Junglyeokdaejosape-tang, Junglyeok-tang Junglyeokdaejosape-tang and Junglyeok-tang has been prescribed for cough, chest pain, and many other similar cases. Cough and chest pain is shown in early lung cancer. That is why we used these prescriptions. Apoptosis happend on the human lung carcinoma A549 cells treated with Jeongiyeokdaejosapye-tang, Jeonglyeok-tang. The concentration-dependent inhibition of cell viability was observed and apoptosis was confirmed by DNA fragmentation. Bcl-2 and COX-2 mRNA expression decreased, but Bax mRNA expression increased, so it was identified with the case of indomethacin known to enhance apoptotic DNA fragmentation. Also expression of the p21, p53, cyclin E, cyclin D1, cytochrome c, caspase-3, and caspase-9 protein increased and the activity of caspase-3 increased, as well. Last, fragmentation of the PARP was shown. The previous and present results indicated that apoptosis of A549 cells by above-mentioned drugs is associated with the blockage of G1/S progression.

• Journal of Ginseng Research
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• v.45 no.1
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• pp.134-148
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• 2021

Background: Lung cancer has a high incidence worldwide, and most lung cancer-associated deaths are attributable to cancer metastasis. Although several medicinal properties of Panax ginseng Meyer have been reported, the effect of ginsenosides Rk1 and Rg5 on epithelial-mesenchymal transition (EMT) stimulated by transforming growth factor beta 1 (TGF-β1) and self-renewal in A549 cells is relatively unknown. Methods: We treated TGF-β1 or alternatively Rk1 and Rg5 in A549 cells. We used western blot analysis, real-time polymerase chain reaction (qPCR), wound healing assay, Matrigel invasion assay, and anoikis assays to determine the effect of Rk1 and Rg5 on TGF-mediated EMT in lung cancer cell. In addition, we performed tumorsphere formation assays and real-time PCR to evaluate the stem-like properties. Results: EMT is induced by TGF-β1 in A549 cells causing the development of cancer stem-like features. Expression of E-cadherin, an epithelial marker, decreased and an increase in vimentin expression was noted. Cell mobility, invasiveness, and anoikis resistance were enhanced with TGF-β1 treatment. In addition, the expression of stem cell markers, CD44, and CD133, was also increased. Treatment with Rk1 and Rg5 suppressed EMT by TGF-β1 and the development of stemness in a dose-dependent manner. Additionally, Rk1 and Rg5 markedly suppressed TGF-β1-induced metalloproteinase-2/9 (MMP2/9) activity, and activation of Smad2/3 and nuclear factor kappa B/extra-cellular signal regulated kinases (NF-kB/ERK) pathways in lung cancer cells. Conclusions: Rk1 and Rg5 regulate the EMT inducing TGF-β1 by suppressing the Smad and NF-κB/ERK pathways (non-Smad pathway).

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.99.2-99.2
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• 2003

One of the major limitations in using adenoviral vector for gene therapy is inefficient infection of host cells. The presence of coxsackievirus and adenovirus receptor (CAR) and ${\alpha}$-integrin on cell surfaces is required for efficient adenovirus infection. In this study, we investigated the effect of trichostatin A, a histone deacetylase inhibitor, on transfection efficiency after transduction of adenovirus mediated p16$\^$INK4a/ gene transfer. In our previous study, p16$\^$INK4a/ tumor suppressor gene transfer in the non-small cell lung cancer cells (A549 cells) by transduction of recombinant adenovirus (Ad5CMV-p16) resulted in significant inhibition of cancer cell proliferation. (omitted)

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.6
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• pp.1563-1567
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• 2005

Mori Cortex Radicis is distributed in Northwestern China, northern Asia, northern Europe, North America, and Korea. This extracts drops sugar in bloods and inhibits cyclic AMP phophodiesterase. In this study, we investigated whether Mori Cortex Radicis would cause apoptotic death of A549 lung cancer cells. To examine the apoptotic effect of Mori Cortex Radicis, cytotoxicity assay, DNA fragmentation analysis, caspase-3 activity assay, and Western blotting for caspase-3, caspase-9 and poly(ADP-ribose) polymerase (PARP) and cytochrome c were performed. Treatment of cells with Mori Cortex Radicis was shown to induce cell death in a dose-dependent manner. DNA fragmentation was made in response to Mori Cortex Radicis. The active fragments of caspase-3, caspase-9 and PARP were almost completely induced and cytochrome c was released following exposure to Mori Cortex Radicis. To elucidate the apoptotic mechanisms, RT-PCR and Western blot analyses for the expression of Bcl-2, Bu and Cox-2 were carried out. Treatment with Mori Cortex Radicis was expressed the reduction of Bcl-2 and Cox-2 and the induction of Bax. Especially p21 and p53 were increased prior to untreated control, while cyclin E and cyclin D1 decreased in the cytosol. These results suggest that the effect Mori Cortex Radicis is associated with the cell cycle arrest and pro-apoptotic cell death in A549 lung cancer cells.

• Molecules and Cells
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• v.38 no.4
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• pp.373-379
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• 2015

Pyruvate kinase M2 isoform (PKM2), a rate-limiting enzyme in the final step of glycolysis, is known to be associated with the metabolic rewiring of cancer cells, and considered an important cancer therapeutic target. Herein, we report a novel PKM2 activator, PA-12, which was identified via the molecular docking-based virtual screening. We demonstrate that PA-12 stimulates the pyruvate kinase activity of recombinant PKM2 in vitro, with a half-maximal activity concentration of $4.92{\mu}M$, and effectively suppresses both anchorage-dependent and -independent growth of lung cancer cells in non-essential amino acid-depleted medium. In addition, PA-12 blocked the nuclear translocalization of PKM2 in lung cancer cells, resulting in the inhibition of hypoxia response element (HRE)-mediated reporter activity as well as hypoxia-inducible factor 1 (HIF-1) target gene expression, eventually leading to the suppression of cell viability under hypoxia. We also verified that the effects of PA-12 were dependent on PKM2 expression in cancer cells, demonstrating the specificity of PA-12 for PKM2 protein. Taken together, our data suggest that PA-12 is a novel and potent PKM2 activator that has therapeutic implications for lung cancer.

• Molecules and Cells
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• v.28 no.6
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• pp.583-588
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• 2009

The peroxiredoxin family of peroxidase has six mammalian members (Prx 1-6). Considering their frequent up-regulation in cancer cells, Prxs may contribute to cancer cells' survival in face of oxidative stress. Here, we show that Prx 6 promotes the invasiveness of lung cancer cells, accompanied by an increase in the activity of phosphoinositide 3-kinase (PI3K), the phosphorylation of p38 kinase and Akt, and the protein levels of uPA. Functional studies reveal that these components support Prx 6-induced invasion in the sequence p38 kinase/PI3K, Akt, and uPA. The findings provide a new understanding of the action of Prx 6 in cancer.

• Reproductive and Developmental Biology
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• v.32 no.2
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• pp.105-110
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• 2008

The endogenous retrovirus-like elements (HERVs) found on several human chromosomes are somehow involved in gene regulation, especially during the transcription level. HERV-H, located on chromosome Xp22, may regulate gastrin-releasing peptide receptor (GRPR) in connection with diverse diseases. By suppression subtractive hybridization screen on SV40-immortalized lung fibroblast (WI-38 VA-13), we discovered that expression of HERV-HX2, a clustered HERV-H sequence on chromosome X, was upregulated in immortalized lung cells, compared to that of normal cells. Expression of HERV-HX2 was then analyzed in various cell lines, including normal somatic cells, cancer cells, SV40-immortalized cells, and undifferentiated and differentiated human embryonic stem cells. Expression of HERV-HX2 was specifically upregulated in continuously-dividing cells, such as cancer cells and SV40-immortalized cells. Especially, HERV-HX2 in HeLa cells was highly upregulated during the S phase of the cell cycle. Similar results were obtained in hES cells, in which undifferentiated cells expressed more HERV-HX2 mRNA than differentiated hES cells, including neural precursor and endothelial progenitor cells. Taken together, our results suggest that HERV-HX2 is upregulated in cancer cells and undifferentiated hES cells, whereas downregulated as differentiation progress. Therefore, we assume that HERV-HX2 may playa role on proliferation of cancer cells as well as differentiation of hES cells in the transcriptional level.

• Journal of Pharmacopuncture
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• v.18 no.1
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• pp.19-26
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• 2015

Objectives: Quercetin, a flavonoid compound, has been reported to induce apoptosis in cancer cells, but its anti-inflammatory effects, which are also closely linked with apoptosis, if any, on non-small-cell lung cancer (NSCLC) have not so far been critically examined. In this study, we tried to determine if quercetin had any demonstrable anti-inflammatory potential, which also could significantly contribute to inducing apoptosis in a NSCLC cell line, A549. Methods: In this context, several assays, including cytotoxicity, flow cytometry and fluorimetry, were done. Gene expression was analyzed by using a western blot analysis. Results: Results revealed that quercetin could induce apoptosis in A549 cells through mitochondrial depolarization by causing an imbalance in B-cell lymphoma 2/Bcl2 Antagonist X (Bcl2/Bax) ratio and by down-regulating the interleukine-6/signal transducer and activator of transcription 3 (IL-6/STAT3) signaling pathway. An analysis of the data revealed that quercetin could block nuclear factor kappa-light-chain-enhancer of activated B cells (NF-${\kappa}B$) activity at early hours, which might cause a down-regulation of the IL-6 titer, and the IL-6 expression, in turn, could inhibit p-STAT3 expression. Down-regulation of both the STAT3 and the NF-${\kappa}B$ expressions might, therefore, cause down-regulation of Bcl2 activity because both are major upstream effectors of Bcl2. Alteration in Bcl2 responses might result in an imbalance in the Bcl2/Bax ratio, which could ultimately bring about mitochondria mediated apoptosis in A549 cells. Conclusion: Overall, the finding of this study indicates that a quercetin induced anti-inflammatory pathway in A549 cells appeared to make a significant contribution towards induction of apoptosis in NSCLC and, thus, may have a therapeutic use such as a strong apoptosis inducer in cancer cells.

• Tuberculosis and Respiratory Diseases
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• v.63 no.1
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• pp.52-58
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• 2007

Background: Photodynamic therapy is a viable option for lung cancer treatment, and many studies have shown that it is capable of inducing cell death in lung cancer cells. However, the precise mechanism of this cell death has not been fully elucidated. To investigate the early changes in cancer cell transcription, we treated A549 cells with the photosensitizer DH-I-180-3 and then we illuminated the cells. Methods: We investigated the gene expression profiles of the the A549 lung cancer cell line, using a DEG kit, following photodynamic therapy and we evaluated the cell viability by performing flow cytometry. We identified the genes that were significantly changed following photodynamic therapy by performing DNA sequencing. Results: The FACS data showed that the cell death of the lung cancer cells was mainly caused by necrosis. We found nine genes that were significantly changed and we identified eight of these genes. We evaluated the expression of two genes, 3-phosphoglycerate dehydrogenase and ribosomal protein S29. The expressed level of carbonic anhydrase XII, clusterin, MRP3s1 protein, complement 3, membrane cofactor protein and integrin beta 1 were decreased. Conclusion: Many of the gene products are membrane-associated proteins. The main mechanism of photodynamic therapy with using the photosensitizing agent DH-I-180-3 appears to be necrosis and this may be associated with the altered production of membrane proteins.