• The Korean Journal of Physiology and Pharmacology
• /
• 제25권4호
• /
• pp.273-280
• /
• 2021

Lung cancer despite advancement in the medical field continues to be a major threat to human lives and accounts for a high proportion of fatalities caused by cancers globally. The current study investigated vanillin oxime, a derivative of vanillin, against lung cancer cells for development of treatment and explored the mechanism. Cell viability changes by vanillin oxime were measured using MTT assay. Vanillin oxime-mediated apoptosis was detected in A549 and NCI-H2170 cells at 48 h of exposure by flow cytometry. The CEBP homologous protein (CHOP) and death receptor 5 (DR5) levels were analysed by RT-PCR and protein levels by Western blotting. Vanillin oxime in concentration-dependent way suppressed A549 and NCI-H2170 cell viabilities. On exposure to 12.5 and 15 μM concentrations of vanillin oxime elevated Bax, caspase-3, and -9 levels in A549 and NCI-H2170 cells were observed. Vanillin oxime exposure suppressed levels of Bcl-2, survivin, Bcl-xL, cFLIP, and IAPs proteins in A549 and NCI-H2170 cells. It stimulated significant elevation in DR4 and DR5 levels in A549 and NCI-H2170 cells. In A549 and NCI-H2170 cells vanillin oxime exposure caused significant (p < 0.05) enhancement in CHOP and DR5 mRNA expression. Vanillin oxime exposure of A549 and NCI-H2170 cells led to significant (p < 0.05) enhancement in levels of phosphorylated extracellular-signal-regulated kinase and c-Jun N-terminal kinase. Thus, vanillin oxime inhibits pulmonary cell proliferation via induction of apoptosis through tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mediated pathway. Therefore, vanillin oxime may be studied further to develop a treatment for lung cancer.

• Nutrition Research and Practice
• /
• 제17권5호
• /
• pp.844-854
• /
• 2023

BACKGROUND/OBJECTIVES: Fucoidan, a polysaccharide content in brown algae, has been reported to inhibit the growth of cancer cells. The present study aimed to investigate the suppression effects of fucoidan on A549 non-small cell lung cancer cells migration. MATERIALS/METHODS: The anti-migratory activity of fucoidan in A549 cells was examined by wound healing assay and phalloidin-rhodamine staining in response to fucoidan (0-100 ㎍/mL) treatment for 48 h. Western blot analysis was performed to clarify the protein expressions relevant to migratory activity. RESULTS: Fucoidan (25-100 ㎍/mL) significantly suppressed A549 cells migration together with reduced the intensity of phalloidin-rhodamine which detect filopodia and lamellipodia protrusions at 48 h of treatment. The protein expression indicated that fucoidan significantly suppressed the phosphorylation of focal adhesion kinase (FAK), Src, and extracellular signal-related kinase (ERK). In addition, the phosphorylation of p38 in A549 cells was found to be increased. CONCLUSIONS: Our data conclude that fucoidan exhibits anti-migratory activities against lung cancer A549 cells mediated by inhibiting ERK1/2 and FAK-Src pathway.

• 대한한방내과학회지
• /
• 제28권3호
• /
• pp.473-491
• /
• 2007

Objectives : This study was designed to investigate the antiproliferative activity of the water extract of Samgibopae-tang (SGBPT) in NCI-H460 and A549 non-small-cell lung cancer cell lines Methods : In this study, we measured the subsistence, form of NCI-H460 and A549 non-small-cell lung cancer cell by hemocytometer and DAPI staining. In each cell, we analyzed DNA fragmentation. reverse transcription-polymerase chain reaction and measured activity of caspase-3, caspase-8 and caspase-9. Results and Conclusions : We found that exposure of A549 cells to SGBPT resulted in growth inhibition in a dose-dependent manner. butSGBPT did not affect the growth of NCI-H460 cells. The antiproliferative effect by SGBPT treatment in A549 cells was associated with morphological changes. SGBPT treatment partially induced the expression of DR5 cells and the expression of Faswas markedly increased in both transcriptional and translational levels in A549 cells. SGBPT treatment partially induced the expression of Bcl-2, Bcl-XL and the expression of Bid was markedly decreased in translational levels in A549 cells. However, SGBPT treatment did not affect the expression of IAP family in A549 orNCI-H460 cells. SGBPT treatment partially induced the expression of caspase-3, caspase-8, caspase-9 activity which markedly increased in a dose-dependent manners in A549 cells. The fragmental development of PARP and ${\beta}$-catenin protein was observed in A549 cells by SGBPT treatment. SGBPT treatment induced the expression of PLC-${\gamma}1$ protein which decreased in A549 cells. SGBPT treatment partially induced the expression of DFF45/ICAD which markedly increased in a dose-dependent manner in A549 cells. Taken together. these findings suggested that SGBPT-induced inhibition of human lung carcinoma did not affect NCI-H460 cell growth. However, SGBPT-induced inhibition of human lung carcinoma A549 cell growth was associated with the induction of death receptor and mitochondrial pathway. The results provided important new insights into the possible molecular mechanisms of the anti-cancer activity of SGBPT.

• 농업생명과학연구
• /
• 제45권5호
• /
• pp.91-96
• /
• 2011

We investigated the inhibitory effects of solvent extracts from Ailanthus altissima in A549 human lung cancer cell. A. altissima has been recognized as a traditional healthy food due to its various biological activities against hypertension, strokes, fever, pain, neuralgia, inflammation, and cancer effects. Recently, it has been reported that the extracts of various wild vegetables show strong anti-cancer properties by induction of apoptosis. However, the mechanisms of their cytotoxicity in human lung cancer cells have been poorly understood. The present study was investigated the effects of solvent extracts from A. altissima on cell growth and apoptosis on A549 human lung cancer cells. A treatment of A. altissima inhibited the growth of A549 cells in a dose-dependent manner by inducing apoptosis. Especially, the chloroform fraction showed the highest anti-cancer effect among five kinds of fractions. And also, induction of apoptosis by chloroform fraction were associated with down-regulation of Bcl-2, and up-regulation of pro-apoptotic Bax expression. From these results, A. altissima may have a therapeutic potential in human lung cancer cells and as a functional food.

• Biomolecules & Therapeutics
• /
• 제20권6호
• /
• pp.513-519
• /
• 2012

Although the immense efforts have been made for cancer prevention, early diagnosis, and treatment, cancer morbidity and mortality has not been decreased during last forty years. Especially, lung cancer is top-ranked in cancer-associated human death. Therefore, effective strategy is strongly required for the management of lung cancer. In the present study, we found that novel daphnane diterpenoids, yuanhualine (YL), yuanhuahine (YH) and yuanhuagine (YG) isolated from the flower of Daphne genkwa (Thymelaeaceae), exhibited potent anti-proliferative activities against human lung A549 cells with the $IC_{50}$ values of 7.0, 15.2 and 24.7 nM, respectively. Flow cytometric analysis revealed that the daphnane diterpenoids induced cell-cycle arrest in the G0/G1 as well as G2/M phase in A549 cells. The cell-cycle arrests were well correlated with the expression of checkpoint proteins including the up-regulation of cyclin-dependent kinase inhibitor p21 and p53 and down-regulation of cyclin A, cyclin B1, cyclin E, cyclin dependent kinase 4, cdc2, phosphorylation of Rb and cMyc expression. In the analysis of signal transduction molecules, the daphnane diterpenoids suppressed the activation of Akt, STAT3 and Src in human lung cancer cells. The daphnane diterpenoids also exerted the potent anti-proliferative activity against anticancer-drug resistant cancer cells including gemcitabine-resistant A549, gefitinib-, erlotinib-resistant H292 cells. Synergistic effects in the growth inhibition were also observed when yuanhualine was combined with gemcitabine, gefitinib or erlotinib in A549 cells. Taken together, these findings suggest that the novel daphnane diterpenoids might provide lead candidates for the development of therapeutic agents for human lung cancers.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권9호
• /
• pp.4039-4044
• /
• 2014

Background: The aim of this study was to investigate the anti-cancer effects and mechanisms of immunochemotherapy of 5-fluorouracil (5-FU) and interleukin-2 (IL-2) on non-small cell lung cancer (NSCLC) A549 cells. Materials and Methods: In order to detect whether 5-FU+IL-2 could effectively inhibit tumor growth in vivo, we established an A549-bearing nude mouse model. The cytotoxicity of natural killer (NK) cells was evaluated using a standard chromium release assay. To evaluate the relevance of NK cells in 5-FU+IL-2-mediated tumor inhibitory effects, we depleted NK cells in A549-bearing mice by injecting anti-asialo-GM-1 antibodies. Effects of 5-FU+IL-2 on the expression and promoter activity of NKG2D ligands (MICA/MICB) in A549 cells in vitro were also assessed. Results: In A549-bearing nude mice, combination therapy significantly inhibited tumor growth in comparison with monotherapy with 5-FU or IL-2 and enhanced the recognition and lysis of tumor cells by NK cells. Further study of mechanisms showed that NK cells played a vital role in the anticancer immune response of 5-FU+IL-2 immunochemotherapy. In addition, the combination therapy synergistically stimulated the expression and promoter activity of MICA/MICB. Conclusions: 5-FU and IL-2 immunochemotherapy significantly inhibited tumor growth and activated NK cytotoxicity in vivo, and these effects were partly impaired after depleting NK cells in tumor-bearing mice. Combination treatment of 5-FU and IL-2 upregulated the expression and the promoter activity of MICA/MICB in A549 cells, which enhanced the recognition of A549 cells by NK cells. All of the data indicated that immunochemotherapy of 5-FU and IL-2 may provide a new treatment option for patients with lung cancer.

• Nutrition Research and Practice
• /
• 제14권2호
• /
• pp.127-133
• /
• 2020

BACKGROUND/OBJECTIVES: Non-small cell lung cancer is mostly recognized among other types of lung cancer with a poor prognosis by cause of chemotherapeutic resistance and increased metastasis. Luteolin has been found to decrease cell metastasis. However, its underlying mechanisms remain unresolved. The objective of this study was to examine the effect (and its mechanism) of luteolin on the migration and invasion of human non-small cell lung cancer A549 cells. MATERIALS/METHODS: Cell viability was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Wound healing and transwell assays were evaluated to assess migration and invasion, respectively. Western blot analysis and immunofluorescence were further performed to investigate the role of luteolin and its mechanisms of action. RESULTS: Administration with up to 40 μM luteolin showed no cytotoxic activity on lung cancer A549 cells or non-cancer MRC-5 cells. Additionally, luteolin at 20-40 μM significantly suppressed A549 cells' migration, invasion, and the formation of filopodia in a concentration-dependent manner at 24 h. This is similar with western blot analysis, which revealed diminished the phosphorylated focal adhesion kinase (pFAK), phosphorylated non-receptor tyrosine kinase (pSrc), Ras-related C3 botulinum toxin substrate 1 (Rac1), cell division control protein 42 (Cdc42), and Ras homolog gene family member A (RhoA) expression levels. CONCLUSIONS: Overall, our data indicate that luteolin plays a role in controlling lung cancer cells' migration and invasion via Src/FAK and its downstream Rac1, Cdc42, and RhoA pathways. Luteolin might be considered a promising candidate for suppressing invasion and metastasis of lung cancer cells.

• Journal of Acupuncture Research
• /
• 제31권1호
• /
• pp.111-119
• /
• 2014

Objectives : I investigated whether Bee Venom can synergistically strengthen the cytotoxic effects of NK-92 cells, enhancing the inhibition of the growth of Lung Cancer Cells including A549 and NCI-H460 through induction of death receptor dependent extrinsic apoptosis and NO generation in the Nitro-oxide pathway. Methods : Bee Venom inhibited cell proliferation of A549 or NCI-H460 Human Lung Cancer Cells as well as NK-92 Cells. Moreover, when they were co-punctured with NK cells and concomitantly treated by 3 ${\mu}g/ml$ of Bee Venom, more influence was exerted on inhibition of proliferation of A549 or NCI-H460 Human Lung Cancer Cells than BV or NK cell co-culture alone. Results : The expression of Fas, TNFR2, DR3, DR6 in A549 Lung Cancer Cells was significantly increased by co-culture of NK-92 cells and treatment of 3 ${\mu}g/ml$ of Bee Venom, compared to co-culture of NK-92 cells alone, whereas the expression of Fas, TNFR2, DR6 in NCI-H460 Lung Cancer Cells was significantly increased by co-culture of NK-92 cells, representing no synergistic effects in the co-culture of NK-92 cell and concomitant treatment of 3 ${\mu}g/ml$ of Bee Venom. Coincidently, caspase-8, a expression of pro-apoptotic proteins in the extrinsic apoptosis pathway demonstrated same results as the above. Meanwhile, In NO generation, there is little change of NO generation in co-culture of NK-92 cells with A549 cells as well as the co-culture of NK-92 cell with them and concomitant treatment of 3 ${\mu}g/ml$ of Bee Venom, whereas increase of NO generation was shown in co-culture of NK-92 cells with NCI-H460 cells as well as the co-culture of NK-92 cell with them and concomitant treatment of 3 ${\mu}g/ml$ of Bee Venom, although synergistic effects by Bee Venom was not found. Conclusions : These present data provide that Bee Venom could be useful candidate compounds to enhance lung cancer growth inhibiting ability of NK-92 cells through DR expression and the related apoptosis.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권7호
• /
• pp.3093-3097
• /
• 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
• /
• 제18권4호
• /
• pp.1147-1152
• /
• 2004

To investigate the anti-cancer effects of aqueous extract of Cheonkumwikyung-tang (CKWKT) on the growth of human lung carcinoma cell line A549, we performed various biochemical experiments such as the effects of CKWKT 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; CKWKT treatment declined the cell viability and proliferation of A549 cells in a concentration-dependent manner. The anti-proliferative effect by CKWKT treatment in A549 cells was associated with morphological changes such as membrane shrinking and cell rounding up. CKWKT treatment induced apoptotic cell death of A549 cells in a concentration-dependent manner, which was associated with inhibition and/or degradation of apoptotic target proteins such poly(ADP-ribose) polymerase, β-catenin and phospholipase C-γ1. Western blot analysis revealed that the levels cyclin-dependent kinase inhibitor p21 expression were induced by CKWKT treatment in A549 cells. Taken together, these findings suggest that CKWKT-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 CKWKT may have therapeutic potential in human lung cancer.