• 동의생리병리학회지
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• 제21권4호
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• pp.973-981
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• 2007

In the present study, we investigated the antiproliferative activity of the water extract of Samgibopae-tang (SGBPT) in NCI-H460 and A549 non-small-cell lung cancer cell lines. We found that exposure of A549 cells to SGBPT resulted in the growth inhibition in a dose-dependent manner as measured by MTT assay, however SGBPT did not affect the growth of NCI-H460 cells. The antiproliferative effect by SGBPT treatment in A549 cells was associated with morphological changes such as membrane shrinking and cell rounding up. SGBPT treatment did not induce the cell cycle arrest in both cell lines, however the frequency of sub-G1 population was concentration-dependently increased by SGBPT treatment in A549 cells. SGBPT treatment partially induced the expression of tumor suppressor p53 in A549 cells and the expression of cyclin-dependent kinase inhibitor p21(WAF1/CIP1) was markedly increased in both transcriptional and translational levels in A549 cells. The up-regulation of p21 by SGBPT occurred in a similar a concentration dependent manner to that observed with the inhibition of cell viability and induction of sub-G1 population of the cell cycle. However SGBPT treatment did not affect other growth regulation-related genes such as early growth response-1 (Egr-1), nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1), inducible nitric oxide synthease (iNOS), cyclooxygenases (COXs), telomere-regulatory factors in A549 as well as NCI-H460 cells. Taken together, these findings suggested that SGBPT-induced inhibition of human lung carcinoma A549 cell growth was aoosciated with the induction of p21 and the results provided important new insights into the possible molecular mechanisms of the anti-cancer activity of SGBPT.

• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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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.

• 동아시아식생활학회지
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• 제14권3호
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• pp.288-293
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• 2004

This study was carried out to determine the antimutagenic and anticancer effects of fermented soybean using Ames test and cytotoxicity, respectively. The ethyl acetate fraction (200 g/plate) of fermented soybean in the Salmonella typhimurium TA100 strain showed 86.6% of inhibition rate against the mutagenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine(MNNG). In addition, the suppression of ethyl acetate fraction with same concentration of fermented soybean in the Salmonella typhimurium TA98 and TAI00 strains showed 82.4% and 90.8% inhibition against 3-amino-l,4-dimethyl-5H-pyrido-(4,3-b)indol (Trp-P-l), respectively. The cytotoxicity effects of fermented soybean against the cell lines with human lung carcinoma (A549), human gastric carcinoma (AGS) and human breast adenocarcinoma (MCF-7) were inhibited with the increase of the extract concentration. The treatment of 1.0 mg/mL ethyl acetate fraction of fermented soybean showed strong cytotoxicities of 71.6%, 91.5% and 80.7% against A549, AGS and MCF-7, respectively.

• 한국식품영양학회지
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• 제22권2호
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• pp.308-312
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• 2009

저분자량 키토산 올리고당의 세포 독성을 실험하였다. 저분자량 키토산 올리고당은 정상세포주인 Vero E6(Africa green monkey kidney cell)에 대한 세포 독성을 거의 나타내지 않았다. 정상세포주에 대한 저분자량 키토산 올리고당의 $IC_{50}$값은 $1,060.28{\mu}g/m{\ell}$이었다. 저분자량 키토산 올리고당은 폐암 세포주인 A549, 방광암 세포주인 J82, 대장암 세포주인 SNU-C4, 위암 세포주인 SNU-1, 유방암 세포주인 ZR75-1 등과 같은 사람의 종양세포주에 대한 in vitro 항종양성을 나타내었다. 종양세포주에 대한 저분자량 키토산 올리고당의 $IC_{50}$값은 A549, J82, SNU-C4, SNU-1, ZR75-1 세포주의 경우에 각각 $477.42{\mu}/m{\ell}$, $480.40{\mu}g/m{\ell}$, $436.84{\mu}g/m{\ell}$, $373.55{\mu}g/m{\ell}$, and $539.95{\mu}/m{\ell}$이었다.

• 한국식품영양학회지
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• 제22권4호
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• pp.639-643
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• 2009

키토산 가수분해물의 세포 독성 및 항종양성 실험에서 키토산 가수분해물은 정상세포주인 Vero E6(Africa green monkey kidney cell)에 대한 세포 독성을 거의 나타내지 않았다. 정상세포주에 대한 키토산 가수분해물의 $IC_{50}$값은 1,107.95 ${\mu}g/m{\ell}$이었다. 키토산 가수분해물은 폐암 세포주인 A549, 방광암 세포주인 J82, 대장암 세포주인 SNU-C4, 위암 세포주인 SNU-1, 유방암 세포주인 ZR75-1 등과 같은 사람의 종양세포주에 대한 in vitro 항종양성을 나타내었다. 종양세포주에 대한 키토산 가수분해물의 $IC_{50}$값은 A549, J82, SNU-C4, SNU-1, ZR75-1 세포주의 경우에 각각 421.06 ${\mu}g/m{\ell}$, 417.99 ${\mu}g/m{\ell}$, 445.54 ${\mu}g/m{\ell}$, 380.65 ${\mu}g/m{\ell}$, and 460.49 ${\mu}g/m{\ell}$이었다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7265-7270
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• 2013

Objective: The present study was designed to investigate the probable mechanisms of synthetic retinoid 4-amino-2-tri-fluoromethyl-phenyl ester (ATPR) inhibition of the proliferation and migration of A549 human lung carcinoma cells. Materials and Methods: After the A549 cells were treated with different concentrations of ATPR or all-trans retinoic acid (ATRA) for 72 h, scratch-wound assays were performed to assess migration. Immunofluorescence was used to determine the distribution of CAV1 and $RXR{\alpha}$, while expression of CAV1, MLCK, MLC, P38, and phosphorylation of MLC and P38 were detected by Western blotting. Results: ATPR could block the migration of A549 cells. The relative migration rate of ML-7 group had significantly decreased compared with control group. In addition, ATPR decreased the expression of a migration related proteins, MLCK, and phosphorylation of MLC and P38. ATPR could also influence the expression of RARs or RXRs. At the same time, CAV1 accumulated at cell membranes, and $RXR{\alpha}$ relocated to the nucleus after ATPR treatment. Conclusions: Caveolae may be implicate in the transport of ATPR to the nucleus. Change in the expression and distribution of $RXR{\alpha}$ may be implicated in ATPR inhibition of A549 cell proliferation. The mechanisms of ATPR reduction in A549 cell migration may be associated with expression of MLCK and phosphorylation of MLC and P38.

• Food Science and Biotechnology
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• 제17권6호
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• pp.1265-1271
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• 2008

Adlay bran is a waste product previously thought to have no commercial value, Its methanolic extract was fractionated using n-hexane (ABM-Hex), ethyl acetate (ABM-EtOAc), 1-butanol (ABM-BuOH), and water (ABM-$H_2O$). The ABM-EtOAc fraction exhibited a strongest inhibition against growth of human lung cancer cell A549 and human colorectal carcinoma cells HT-29 and COLO 205. Inhibition of cell cycle progression at $G_0/G_1$ transition, increase of cells at the sub-$G_1$ phase, and DNA ladders were observed in cells treated with ABM-EtOAc. The ABM-BuOH fraction showed the strongest inhibition of proinflammatory cytokines tumor necrosis factor (TNF)-$\alpha$ and interlukin (IL)-$1{\beta}$ in stimulated RAW 264.7 macrophages. Further, ABM-EtOAc and ABM-BuOH inhibited cyclooxygenase (COX)-2 expression in A549 and HT-29 carcinoma cells, while COX-l expression was not affected. These results reveal that both ABM-EtOAc and ABM-BuOH may aid the prevention of cancers and the applications in cancer chemotherapy.

• 동의생리병리학회지
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• 제17권1호
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• pp.213-219
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• 2003

We investigated the effects of Insamsapye-tang (ISSPT) water extract on the cell proliferation of human lung carcinoma A549 cells. ISSPT treatment resulted in the inhibition of cell proliferation in a concentration-dependent manner. This anti-proliferative effect of A549 cells by ISSSPT treatment was associated with morphological changes such as membrane shrinking and cell rounding up. DNA flow cytometric histograms showed that population of G1 phase of the cell cycle was increased by ISSPT treatment in a concentration-dependent manner. ISSPT treatment induced the levels of tumor suppressor p53 protein and cyclin-dependent kinase (Cdk) inhibitor p27 without significant alteration of cyclins and Cdks expression. In addition, ISSPT treatment resulted in down-regulation of phosphorylated retinoblastoma protein (pRB). However, the levels of p130, the pRB family protein, and transcription factors. E2F-1 and E2F-4. were remained unchanged. The present results indicated that ISSPT-induced inhibition of lung cancer cell proliferation is associated with the blockage of G1/S progression and the induction of apoptosis, and we suggest that ISSPT will be an effective therapeutic agent on human lung cancer.

• 대한의생명과학회지
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• 제28권4호
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• pp.247-259
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• 2022

Immunotherapy, which uses an immune mechanism in the body, has received considerable attention for cancer treatment. Suberoylanilide hydroxamic acid (SAHA), also known as a histone deacetylase inhibitor (HDACi), is used as a cancer treatment to induce active immunity by increasing the expression of T cell-induced chemokines. However, this SAHA treatment has the disadvantage of causing PD-L1 overexpression in tumor cells. In this study, we prevented PD-L1 overexpression by blocking the PD-1/PD-L1 pathway using PD-L1 siRNA. We designed two types of liposomes, the neutral lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholin (POPC) for SAHA, and 1,2-dioleoyl-3-trimethylammoniumpropane (DOTAP) for siRNA. To effectively target PD-L1 in cancer cells, we conjugated PD-L1 antibody with liposomes containing SAHA or PD-L1 siRNA. These immunoliposomes were also evaluated for cytotoxicity, gene silencing, and T-cell-induced chemokine expression in human non-small cell lung cancer A549 cells. It was confirmed that the combination of the two immunoliposomes increased the cancer cell suppression efficacy through Jurkat T cell induction more than twice compared to SAHA alone treatment. In conclusion, this combination of immunoliposomes containing a drug and nucleic acid has promising therapeutic potential for non-small-cell lung carcinoma (NSCLC).

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.5895-5900
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• 2013

Dictamnine (Dic) has the ability to exert cytotoxicity in human cervix, colon, and oral carcinoma cells and dihydroartemisinin (DHA) also has potent anticancer activity on various tumour cell lines. This report explores the molecular mechanisms by which Dic treatment and combination treatment with DHA and Dic cause apoptosis in human lung adenocarcinoma A549 cells. Dic treatment induced concentration- and time-dependent cell death. FCM analysis showed that Dic induced S phase cell cycle arrest at low concentration and cell apoptosis at high concentration in which loss of mitochondrial membrane potential (${\Delta}{\Psi}m$) was not involved. In addition, inhibition of caspase-3 using the specific inhibitor, z-DQMD-fmk, did not attenuate Dic-induced apoptosis, implying that Dic-induced caspase-3-independent apoptosis. Combination treatment with DHA and Dic dramatically increased the apoptotic cell death compared to Dic alone. Interestingly, pretreatment with z-DQMD-fmk significantly attenuated DHA and Dic co-induced apoptosis, implying that caspase-3 plays an important role in Dic and DHA co-induced cell apoptosis. Collectively, we found that Dic induced S phase cell cycle arrest at low concentration and cell apoptosis at high concentration in which mitochondria and caspase were not involved and DHA enhanced Dic induced A549 cell apoptosis via a caspase-dependent pathway.