Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study, we describe the cytotoxicity of the new drug prodigiosin (PG) in two small cell lung carcinoma (SCLC) cell lines, GLC4 and its derived doxorubicin-resistant GLC4/ADR cell line, which overexpresses multidrug-related protein 1 (MRP-1). We observed through Western blot that PG mediated cytochrome c release, caspase cascade activation and PARP cleavage, thereby leading to apoptosis in a dose-response manner. MRP-1 expression increased after PG treatment, although that does not lead to protein accumulation. The MTT assay showed no difference in sensitivity to PG between the two cell lines. Our results support PG as a potential drug for the treatment of lung cancer as it overcomes the multidrug resistance phenotype produced by MRP-1 overexpression.
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PMID:High cytotoxic sensitivity of the human small cell lung doxorubicin-resistant carcinoma (GLC4/ADR) cell line to prodigiosin through apoptosis activation. 1574 75

Angiogenesis is becoming a major target for antitumor therapies, and identifying new angiogenic factors and their specific inhibitors may provide new avenues for tumor management. Here we identify gastrin-releasing peptide (GRP) as a new angiogenic molecule that is secreted by tumors and acts directly upon GRP receptors in the endothelial cells. Addition of GRP increases endothelial cell migration and cord formation in vitro, and induces angiogenesis in an in vivo assay. We have recently identified a small molecule GRP blocker, compound 77427. This inhibitor significantly reduced endothelial cell cord formation in vitro and angiogenesis in vivo. Conversely, when applied to VEGF-induced angiogenesis, the small molecule did not have any effect, demonstrating its specificity. Furthermore, this GRP blocker was able to reduce lung tumor cell growth in vitro as demonstrated by MTT and clonogenic assays. When applied to a xenograft model with lung cancer cells, compound 77427 reduced tumor volume to undetectable sizes, although when the treatment was suspended, tumors began to grow again at normal rates. Our collective observations indicate that GRP is a new angiogenic peptide and that its inhibition offers an attractive tool to reduce tumor burden.
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PMID:Gastrin-releasing peptide (GRP) induces angiogenesis and the specific GRP blocker 77427 inhibits tumor growth in vitro and in vivo. 1575 Jun 18

Chemotherapy for lung cancer not only has severe side effects but frequently also exhibits limited, if any clinical effectiveness. Dexamethasone (DEX) and similar glucocorticoids (GCs) such as prednisone are often used in the clinical setting, for example, as cotreatment to prevent nausea and other symptoms. Clinical trials evaluating the impact of GCs on tumour control and patient survival of lung carcinoma have never been performed. Therefore, we isolated cancer cells from resected lung tumour specimens and treated them with cisplatin in the presence or absence of DEX. Cell number of viable and dead cells was evaluated by trypan blue exclusion and viability was measured by the MTT-assay. We found that DEX induced resistance toward cisplatin in all of 10 examined tumour samples. Similar results were found using gemcitabine as cytotoxic drug. Survival of drug-treated lung carcinoma cells in the presence of DEX was longlasting as examined 2 and 3 weeks after cisplatin treatment of a lung carcinoma cell line. These data corroborate recent in vitro and in vivo xenograft findings and rise additional concerns about the widespread combined use of DEX with antineoplastic drugs in the clinical management of patients with lung cancer.
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PMID:Dexamethasone-induced cisplatin and gemcitabine resistance in lung carcinoma samples treated ex vivo. 1575 74

A series of synthetic (nonylphenol, diethylstilbestrol, and bisphenol A) and natural (quercetin, resveratrol, and genistein) phenolic estrogens were investigated for their ability to affect the viability and proliferation of A549 lung cancer cells. To assess and distinguish the cytotoxic effect of individual estrogens, we used both the MTT tetrazolium spectrophotometric method and the fluorescence assay, while the induction of the cell specific apoptotic process was examined by fluorescence microscopy after treatment of cells with SYTO 24 green fluorescent dye. A systematic study of interferences for both fluorescence and MTT methods is presented. The results showed that both natural and synthetic estrogens decreased the viability and proliferation of A549 lung cancer cells in a dose-dependent manner but at different sensitivities. Nonylphenol appeared very different as compared to the other estrogens, acting by inducing the higher inactivation rate of the cells within a very short time. The cytotoxic effect of the estrogens was directly related to their structural and conformational characteristics including chain length, number, and position of hydroxyl groups and degree of saturation.
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PMID:Effect of natural and synthetic estrogens on a549 lung cancer cells: correlation of chemical structures with cytotoxic effects. 1577 86

Coumarin and its derivative 7-hydroxycoumarin (7-OHC) have antitumor and antimetastatic properties. The purpose of this study was to investigate the possible effects of these compounds on expression of the bcl-2 and Bax oncoproteins in two human lung cancer cell lines, A427 and Calu-1. The cells were cultured in vitro for 24 h in RPMI 1640 with 1.5% (v/v) ethanol, 1.0 mM ethanolic coumarin or 1.0 mM ethanolic 7-OHC. Viability was determined in each cell line by an MTT assay. Total protein was extracted from cell lysates and the bcl-2 and Bax oncoproteins were identified. Western blotting showed a decrease in bcl-2 and an increase in Bax in A427 cells cultured with coumarin or 7-OHC. Neither drug changed bcl-2 expression in Calu-1 cells compared to solvent controls, and Bax expression was only slightly increased by coumarin. We conclude that 7-OHC is a more potent inhibitor of cell proliferation than coumarin and has more marked effects on oncoprotein expression. Also, the A427 cell line was more sensitive to the drugs than Calu-1.
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PMID:Effects of coumarin and 7OH-coumarin on bcl-2 and Bax expression in two human lung cancer cell lines in vitro. 1596 20

Lung cancer has emerged as a leading cause of cancer death in the world. Non-small cell lung cancer (NSCLC) accounts for 75-80% of all lung cancers. Current therapies are ineffective, thus new approaches are needed to improve the therapeutic ratio. Double stranded RNA (dsRNA)-mediated RNA interference (RNAi) has shown promise in gene silencing, the potential of which in developing new methods for the therapy of NSCLC needs to be tested. We report here RNAi induced effective silencing of the epidermal growth factor receptor (EGFR) gene, which is over expressed in NSCLC. NSCLC cell lines A549 and SPC-A1 were transfected with sequence- specific dsRNA as well as various controls. Immune fluorescent labeling and flow cytometry were used to monitor the reduction in the production of EGFR protein. Quantitative reverse-transcriptase PCR was used to detect the level of EGFR mRNA. Cell count, colony assay, scratch assay, MTT assay in vitro and tumor growth assay in athymic nude mice in vivo were used to assess the functional effects of EGFR silencing on tumor cell growth and proliferation. Our data showed transfection of NSCLC cells with dsRNA resulted in sequence specific silencing of EGFR with 71.31% and 71.78 % decreases in EGFR protein production and 37.04% and 54.92% in mRNA transcription in A549 and SPC-A1 cells respectively. The decrease in EGFR protein production caused significant growth inhibition, i.e.: reducing the total cell numbers by 85.0% and 78.3%, and colony forming numbers by 63.3% and 66.8%. These effects greatly retarded the migration of NSCLC cells by more than 80% both at 24 h and at 48 h, and enhanced chemo-sensitivity to cisplatin by four-fold in A549 cells and seven-fold in SPC-A1. Furthermore, dsRNA specific for EGFR inhibited tumor growth in vivo both in size by 75.06% and in weight by 73.08%. Our data demonstrate a new therapeutic effect of sequence specific suppression of EGFR gene expression by RNAi, enabling inhibition of tumor proliferation and growth. However, in vivo use of dsRNA for gene transfer to tumor cells would be limited because dsRNA would be quickly degraded once delivered in vivo. We thus tested a new bovine lentiviral vector and showed lentivector-mediated RNAi effects were efficient and specific. Combining RNAi with this gene delivery system may enable us to develop RNAi for silencing EGFR into an effective therapy for NSCLC.
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PMID:Silencing the epidermal growth factor receptor gene with RNAi may be developed as a potential therapy for non small cell lung cancer. 1598 32

Cooking oil fumes (COF) exposure was demonstrated to be associated with lung cancer development in Taiwanese nonsmoking women. Previous studies identified Cox-2 overexpression and oxidative DNA damage in lung adenocarcinoma cells after exposure to COF. Involvement of COF in lung tumorigenesis may be associated with cell survival, as well as proliferation of lung adenocarcinoma. To test this hypothesis, A549, a lung adenocarcinoma cell line, was used, and MTT assay data showed that the cell viability of A549 was significantly increased in a concentration-dependent manner by COF treatment for 48 h. Flow cytometery results indicated that the proportion of A549 cell at S-phase was markedly increased after exposure of COF. To elucidate whether the anti-apoptotic c-IAP2 (IAP2) was involved in COF-improved cell survival, IAP2 protein levels was determined by Western blot, and the results showed it was significantly induced by COF in a concentration-dependent manner. Moreover, the suppression of BAY, a nuclear factor (NF)-kappaB binding inhibitor, or the COF-induced IAP2 protein levels indicated that NF-kappaB activation by COF may partly be involved in IAP2 induction. These results showed that the positive impact of COF on cell survival and proliferation of A549 lung tumor cells may be through an induction of IAP2 overexpression.
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PMID:Cooking oil fumes improve lung adenocarcinoma cell survival through c-IAP2 induction. 1607 64

Calcitriol is a potent antiproliferative agent against various tumour cells in vitro. Its biological activity is mediated by the vitamin D receptors (VDRs). Here, we present the results of a study on vitamin D3 compounds (calcitriol and its analogue PRI-2191) as potential agents in combined antitumour therapy in vitro. Applying antiproliferative SRB and MTT assays, we measured the growth inhibitory effects of vitamin D compounds applied alone or in combination with either cisplatin or doxorubicin. Next, we examined the correlation of this effect with the presence of nVDR (nuclear VDR). The following cancer cell lines were applied: HL-60 (human leukaemia), SW707 (human colon cancer), A549 (human lung cancer), WEHI-3 (mouse leukaemia). The treatment of tumour cells with the combination of vitamin D compounds and cytostatics decreased the inhibitory concentration 50% (IC50) values compared with the effects of cytostatics applied alone. The synergistic effect was positively correlated with nVDR expression.
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PMID:Correlation between VDR expression and antiproliferative activity of vitamin D3 compounds in combination with cytostatics. 1615 69

An alpha-tocopherol, beta-carotene supplementation trial (ATBC) and a chemoprevention trial with beta-carotene and retinoids (CARET trial) were conducted in the 1990s in populations at risk for the development of lung cancer. Both trials had to be discontinued due to significant increases in lung cancer and cardiovascular mortality. Clinical trials to test the cancer preventive effects of beta-carotene are still ongoing, and high concentrations of this provitamin are contained in numerous dietary supplements. Using a cell line derived from a human pulmonary adenocarcinoma (PAC) of Clara cell lineage and immortalized human small airway epithelial cells, our data show that low concentrations of beta-carotene that can be realistically expected in human tissues after oral administration caused a significant increase in intracellular cAMP and activated PKA, as well as in phosphorylation of ERK1/2 and CREB. Furthermore, the proliferation of cells was significantly stimulated by identical concentrations of beta-carotene as monitored by MTT assays. Control experiments with retinol also showed stimulation of cell proliferation and activation of PKA in both cell lines. In light of the fact that PAC is the leading type of lung cancer, these findings suggest that the growth promoting effects of beta-carotene on this cancer type observed in our experiments may have contributed to the unfortunate outcome of the ATBC and CARET trials. This interpretation is supported by the fact that elevated levels of cAMP in the cardiovascular system play a major role in the genesis of cardiovascular disease, which was also greatly promoted in the CARET trial. Our data challenge the widely accepted view that beta-carotene may be useful as a cancer preventive agent.
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PMID:Growth stimulation of human pulmonary adenocarcinoma cells and small airway epithelial cells by beta-carotene via activation of cAMP, PKA, CREB and ERK1/2. 1620 75

Smoking is a risk factor for lung cancer, chronic obstructive pulmonary disease, chronic bronchitis and asthma. The chronic lung diseases are also a predisposing factor for the development of lung cancer. Glucocorticoids are used for the management of chronic lung diseases because of their anti-inflammatory activity. These drugs also have anti-tumourigenic effects in mouse models of lung cancer. Glucocorticoids are frequently used as co-treatment with cancer therapy. Using the human pulmonary adenocarcinoma (PAC) cell line NCI-H322 with features of bronchiolar Clara cells, and immortalised human small airway epithelial cells, our data show that the glucocorticoid dexamethasone increased cell proliferation in MTT assays in a PKA-dependent manner. Dexamethasone significantly increased intracellular cAMP in direct immunoassays. Immunoblot analysis revealed increased phosphorylation of ERK1/2 and of the transcription factor CREB in response to dexamethasone. These data suggest that glucocorticoids could have tumour promoting activity on a sub-set of human PAC.
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PMID:PKA-dependent growth stimulation of cells derived from human pulmonary adenocarcinoma and small airway epithelium by dexamethasone. 1623 8


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