• Asian Pacific Journal of Cancer Prevention
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• 제15권7호
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• pp.3093-3097
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• 2014

Background: Cancer is a major threat to the public health whether in developed or in developing countries. As the most common primary malignant tumor, the morbidity and mortality rate of lung cancer continues to rise in recent ten years worldwide. Chemotherapy is one of the main methods in the treatment of lung cancer, but this is hampered by chemotherapy drug resistance, especially MDR. As a component of the 60S large ribosomal subunit, ribosomal protein L39-L gene was reported to be expressed specifically in the human testis and human cancer samples of various tissue origins. Materials and Methods: Total RNA of cultured drug-resistant and susceptible A549 cells was isolated, and real time quantitative RT-PCR were used to indicate the transcribe difference between amycin resistant and susceptible strain of A549 cells. Viability assay were used to show the amycin resistance difference in RPL39-L transfected A549 cell line than control vector and null-transfected A549 cell line. Results: The ribosomal protein L39-L transcription level was 8.2 times higher in drug-resistant human lung cancer A549 cell line than in susceptible A549 cell line by quantitative RT-PCR analysis. The ribosomal protein L39-L transfected cells showed enhanced drug resistance compared to plasmid vector-transfected or null-transfected cells as determined by methyl tritiated thymidine (3H-TdR) incorporation. Conclusions and Implications for Practice: The ribosomal protein L39-L gene may have effects on the drug resistance mechanism of lung cancer A549 cells.

• 동의생리병리학회지
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• 제18권4호
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• pp.1102-1106
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• 2004

To investigate the anti-proliferative effects of an aqueous extract of Cordyceps militaris (AECM) on the growth of human lung carcinoma cell line A549, we performed various biochemical experiments such as the effects of AECM on the cell proliferation and viability, the morphological changes, the effects on expression of apoptosis and cell growth-regulatory gene products. Results obtained are as follow; AECM treatment declined the cell viability and proliferation of A549 cells in a concentration-dependent manner. The anti-proliferative effect by AECM treatment in A549 cells was associated with morphological changes such as membrane shrinking and cell rounding up. Taken together, these findings suggest that AECM-induced inhibition of human lung cancer cell proliferation is associated with the induction of apoptotic cell death via regulation of several major growth regulatory gene products, and C. militaris may have therapeutic potential in human lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권18호
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• pp.7825-7829
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• 2014

Objective: To investigate the effect of high expression of XAF1 in vivo or in vitro on lung cancer cell growth and apoptosis. Methods: 1. The A549 human lung cancer cell line was transfected with Ad5/F35 - XAF1, or Ad5/F35 - Null at the same multiplicity of infection (MOI); (hereinafter referred to as transient transfected cell strain); XAF1 gene mRNA and protein expression was detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting respectively. 2. Methyl thiazolyl tetrazolium (MTT) and annexin V-FITC/PI double staining were used to detect cell proliferation and apoptosis before and after infection of Ad5/F35 - XAF1 with Western blotting for apoptosis related proteins, caspase 3, caspase - 8 and PARP. 3. After the XAF1 gene was transfected into lung cancer A549 cells by lentiviral vectors, and selected by screening with Blasticidin, reverse transcription polymerase chain reaction (RT-PCR) and Western blotting were applied to detect mRNA and protein expression, to establish a line with a stable high expression of XAF1 (hereinafter referred to as stable expression cell strain). Twenty nude mice were randomly divided into groups A and B, 10 in each group: A549/XAF1 stable expression cell strain was subcutaneously injected in group A, and A549/Ctrl stable cell line stable expression cell strain in group B (control group), to observe transplanted tumor growth in nude mice. Results: The mRNA and protein expression of XAF1 in A549 cells transfected by Ad5/F35 - XAF1 was significantly higher than in the control group. XAF1 mediated by adenovirus vector demonstrated a dose dependent inhibition of lung cancer cell proliferation and induction of apoptosis. This was accompanied by cleavage of caspase -3, -8, -9 and PARP, suggesting activation of intrinsic or extrinsic apoptotic pathways. A cell strain of lung cancer highly expressing XAF1 was established, and this demonstrated delayed tumor growth after transplantation in vivo. Conclusion: Adenovirus mediated XAF1 gene expression could inhibit proliferation and induce apoptosis in lung cancer cells in vitro; highly stable expression of XAF1 could also significantly inhibit the growth of transplanted tumors in nude mouse, with no obvious adverse reactions observed. Therefore, the XAF1 gene could become a new target for lung cancer treatment.

• Environmental Analysis Health and Toxicology
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• 제18권1호
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• pp.15-19
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• 2003

Metallothionein gene expression activity of cadmium was investigated in a human lung epithelial cell line. Cells, grown to near confluence, were exposed to 0∼10 ${\mu}$M Cd metal for 6 hours. Cadmium did not cause morphological alteration in lung epithelial cells that are characteristic of cell damages such as cell shrinkage, detachment of the cell from its neighbors, cytoplasmic and chromatic condensation. However, metallothionein genes of MT-1 and MT-2 were rapidly induced in the treated cell measured by RT-PCR. Regarding the induction pattern of motallothionein mRNA, MT-1 mRNA was induced in a dependent manner. MT-2 mRNA induction, which was measured using oligo primers based on cDNA of human reticulocytes, seemed to be slightly increased in low doses but decreased at high concentration used in the experiment.

• 대한약침학회지
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• 제18권1호
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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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• 제43권1호
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• pp.63-68
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• 1996

연구배경: 인터페론감마-(interferon-$\gamma$)는 항바이러스 효과, 암세포의 형증식 효과, 대식세포 및 B 림프구의 활성화, 주면역복합체(MHC) 항원 발현의 증가 등의 생물학적 효과를 나타낸다. 특히, 인터페론감마의 항암 효과는 이미 생체 내외에서 입증되어 실제 폐암 환자에 대한 임상 연구가 시도되고 있다. 그러나, 인터페론감마의 항암효과 기전은 여러가지 가설이 제시되기는 하고 있지만 아직 확립된 것이 없다. 세포의 괴사(necrosis)는 심한 외부의 스트레스에 의해서 발생하는 세포 사망의 형태로 잘 알려져 있다. 생명현상 중 괴사와는 전혀 다른 세포 사망의 과정으로 아포프토시스(apoptosis)가 있다. 아포프토시스는 조직의 항상성(homeostasis of tissue volume), 개체의 발생과정, 장기의 퇴행(regression), tolerance 등의 여러 생명 활동 과정에서 발생하는 세포 사망의 과정으로서, 세포질 및 핵이 분절화(fragmentation)되어 죽어가는 능동적 사망과정으로 알려져 있다. 아포프토시스에서는 수동적으로 죽어가는 괴사에서 볼 수 없는 DNA 분절화(DNA ladder pattern)가 특징적으로 관찰된다. 인터페론감마의 암세포에 대한 세포독성 기전을 연구하기 위해서 인터페론감마를 폐암세포주인 A549세 처치한 후 현미경(inverted microscope)로 A549의 변화를 관찰하였는데 A549세포가 분절화되면서 죽어가는 것을 관찰할 수 있었다. 저자들은 인터페론감마의 항암기전으로서 아포프토시스의 가능성을 평가하고자 본 연구를 시행하였다. 방법: 폐암세포주인 A549세포를 대상으로 하였다. A549세포에 여러 농도의 인터페론감마를 투여하고 24시간, 72시간, 120시간 후에 MTT(dimethylthiazolyl diphenyltetrazolium bromide) bioassay법으로 세포독성을 정량화하였다. 그리고, 100 unit/ml의 인터페론감마를 A549 세포에 120시간 처치 후, 광학 현미경으로 세포 사망의 양상을 관찰하였다. 또한, 100 unit/ml의 인터페론감마를 투여하고 120시간이 경과한 후 사망 세포의 DNA를 추출하여 1.5% agarose gel에서 전기 영동을 시행하고 ethidium bromide로 염색 후 DNA ladder pattern 유무를 관찰하였다. 결과: 1) 인터페론감마에 의한 A549 폐암세포주의 세포독성 효과는 24시간에는 거의 없다가 72시간부터 120시간 사이에 나타나기 시작하여 120시간에는 더 증가하였다. 2) 인터페론감마에 의한 A549 세포의 사망 양상은 광학현미경상 A549 세포들이 작은 분절로 나뉘면서 사망하였다. 3) 인터페론감마를 A549 폐암세포주에 처치 후 죽어기는 세포의 DNA를 추출하여 전기영동시킨 결과 아포프토시스(apoptosis)에서 특징적으로 보이는 DNA ladder pattern을 관찰할 수 있었다. 결론: 인터페론감마(interferon-$\gamma$)의 A549 폐암세포주에 대한 세포독성의 기전은 아포프토시스 과정을 통해서 일어난다.

• Asian Pacific Journal of Cancer Prevention
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• 제17권11호
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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.

• 동의생리병리학회지
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• 제16권3호
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• pp.521-527
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• 2002

The Caesalpinia sappan is widely used in the traditional oriental herbal medicine for anti-inflammatory, antioxidant effects. The effects of water extract of C. sappan on the cell viability and induction of apoptosis were investigated in human lung cancer cell line A549. The water extract of C. sappan produced apoptotic cell death and DNA fragmentation and nucleus chromatin condensation in A549 cells. The enzyme activity of caspase-3 and protein level of actived caspase-3 were markedly increased in A549 cells treated with the water extract of C. sappan. In addition, the extract of C. sappan induced cleavage of Poly (ADP-ribose) polymerase (PARP), a known substrate for caspase-3, and dropped in cellular ATP levels. These results suggest that the extract of C. sappan exerts anticancer activity by induction of apoptosis via activation of caspase-3, cleavage of PARP protein, and depletion of cellular ATP levels in A549 cells.

• 디지털융복합연구
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• 제14권1호
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• pp.491-496
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• 2016

본 논문은 야채추출물의 인간 암세포 증식 억제효과를 살펴보는 데 목적이 있다. 본 연구는 일반적으로 야채수프에 사용되는 무, 무청, 우엉, 표고버섯, 당근등의 야채추출물을 이용하여 암세포 증식 억제효과를 살펴보았다. 인간 암세포주는 위암 (AGS) 세포주, 급성 전골수성 백혈병 (HL-60) 세포주, 폐암 (A549) 세포주를 사용하였으며 MTS방법으로 암세포 증식 억제를 확인하였다. 위암 세포주는 표고버섯과 당근에서 암세포 증식 억제효과가 있었으며 급성 전골수성 백혈병 세포주는 무청, 우엉, 당근에서 암세포 증식 억제효과가 있었으며 특히 우엉과 당근에서 유의성 있는 억제를 보였으며 폐암 세포주는 무, 무청에서 탁월한 효과를 보였다. 암세포 증식억제 효과가 있는 야채추출물을 이용한 야채스프는 항암성이 있는 기능성 소재로 활용과 융복합적인 웰리스를 위한 기초 자료로 활용이 가능하다고 사료된다.

• 대한화학회지
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• 제55권5호
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• pp.765-775
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• 2011

Novel analogs of bortezomib were designed, synthesized and in vitro biological evaluation was carried out using human tumor cell lines A549 and PC3. Docking studies of these analogs of bortezomib was discussed. According to biological investigations, the inhibitors 4, 6, and 8 were found to be more potent than reference drug candidate bortezomib. A549 cell line showed significant sensitivity towards 4, 6, and 8 with $IC_{50}$ values 14.03, 18.5, and 12.4 nM, respectively, and PC3 cell line showed IC50 values 26.1, 37.0, and 21.2 nM, respectively. The $IC_{50}$ values of bortezomib in these cell lines are 27.3 nM and 42.0 nM.