Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0007131 (non-small cell lung cancer)
 22,601 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several experiments have demonstrated that pineal gland plays a physiological anticancer role. Melatonin (MLT), its most investigated hormone, is a natural anticancer agent. However, MLT would not be the only endocrine molecule responsible for the anticancer property of the pineal gland. In fact, another pineal indole hormone, the 5-methoxytryptamine (5-MTT), has appeared to exert in vitro an antitumour activity superior to that of MLT itself. Previous studies have already shown the therapeutic anticancer action of MLT in association with chemotherapy also in human neoplasms. This study was performed to evaluate the influence of 5-MTT at physiological doses (1 mg/day orally during light phase) on the efficacy of chemotherapy with cisplatin plus etoposide in advanced non-small cell lung cancer patients with respect to that obtained in patients treated by chemotherapy alone or chemotherapy plus pharmacological doses of MLT (20 mg/day orally during the dark phase of the day). The study included 100 patients, who were randomised to receive chemotherapy alone or in association with MLT or 5-MTT. The overall response rate achieved in both patients concomitantly treated with MLT or 5-MTT was significantly higher with respect to that obtained in patients treated with chemotherapy alone. Moreover, both MLT and 5-MTT significantly reduced some chemotherapy-related toxicities, namely thrombocytopenia and neurotoxicity. This preliminary study shows that less known pineal hormone 5-MTT may exert at low doses the same anticancer therapeutic effect in association with chemotherapy, which may be obtained by pharmacological doses of the most investigated pineal hormone MLT.
 ...
PMID:Biochemotherapy with immunomodulating pineal hormones other than melatonin: 5-methoxytryptamine as a new oncostatic pineal agent. 1745 89

Nicotinic acetylcholine receptors (nAChR) are expressed on normal bronchial epithelial and nonsmall cell lung cancer (NSCLC) cells and are involved in cell growth regulation. Nicotine induced cell proliferation. The purpose of this study was to determine if interruption of autocrine nicotinic cholinergic signaling might inhibit A549 NSCLC cell growth. For this purpose alpha-Cobratoxin (alpha-CbT), a high affinity alpha7-nAChR antagonist was studied. Cell growth decrease was evaluated by Clonogenic and MTT assays. Evidence of apoptosis was identified staining cell with Annexin-V/PI. Characterization of the basal NF-kappaB activity was done using the Trans-AM NF-kappaB assay colorimetric kit. "In vivo" antitumour activity was evaluated in orthotopically transplanted nude mice monitored by In vivo Imaging System technology. alpha-CbT caused concentration-dependent cell growth decrease, mitochondrial apoptosis caspases-9 and 3-dependent, but caspase-2 and p53-independent and down-regulation of basal high levels of activated NF-kappaB. alpha-CbT treatment determines a significant reduction of tumor growth in nude mice orthotopically engrafted with A549-luciferase cells (4.6% of living cells vs. 31% in untreated mice). No sign of toxicity was reported related to treatment. These findings suggest that alpha7-nAChR antagonists namely alpha-CbT may be useful adjuvant for treatment of NSCLC and potentially other cancers.
 ...
PMID:Natural agents targeting the alpha7-nicotinic-receptor in NSCLC: a promising prospective in anti-cancer drug development. 1806 32

Constitutive expression of cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) occurs frequently in non-small cell lung cancer (NSCLC). Anticancer research targeting EGFR has got an extensive attention especially in NSCLC and COX-2 inhibitor also shown a certain anticancer activity in recent years. Simultaneously targeting COX-2 and EGFR may be a promising therapeutic way. We carried out the in vitro study using selective COX-2 inhibitor celecoxib combined with EGFR-tyrosine kinase inhibitor (EGFR-TKI) ZD1839 on NSCLC cell lines to investigate the anti proliferation effect and the cell molecular mechanism. MTT growth assay showed the synergistic therapeutic effect of certain concentration of celecoxib combined with ZD1839 and synergistic apoptosis effect was detected by Hoechest33258 fluorescence staining and flow cytometric analysis. In western blot analysis, ZD1839 single agent inhibited the activation of EGFR and downstream cell signal transduction AKT and extrocellular signal-regulated kinase (ERK) pathways, the transcription activity of nuclear factor-kappa B (NF-kappaB), and the expression of COX-2. Celecoxib single agent could also inhibit AKT and ERK pathway in NSCLC, even the EGFR expression under high concentration treatment. Celecoxib combined with ZD1839 led to stronger inhibition of related cell signal transduction pathways in NSCLC.
 ...
PMID:Selective COX-2 inhibitor celecoxib combined with EGFR-TKI ZD1839 on non-small cell lung cancer cell lines: in vitro toxicity and mechanism study. 1817 86

Gemcitabine is a chemotherapeutic drug widely used in the treatment of non-small cell lung carcinoma, especially in advanced lung adenocarcinoma. However, many patients with advanced lung adenocarcinoma show a resistance to gemcitabine. Overexpression of COX-2 has been found in human non-small cell lung cancer tissues and itA s cell lines. Evidences show that COX-2 is involved in drug resistance of tumor. However, It is unknown whether COX-2 inhibitor can augment the efficacy of gemcitabine against lung adenocarcinoma. In this study, A549 cells were treated with gemcitabine and/or NS-398. The cell viability was examined by MTT assay. The cell cycle distribution and apoptotic ratio were tested by flow cytometry. The levels of p21WAF1, p27KIP1, p16INK4a and p15INK4b expression were detected by western blotting. After the cells were treated with gemcitabine along with NS-398, more cells were arrested in G1 phase and went to apoptosis. The levels of p21WAF1 and p27KIP1 protein were elevated, while the levels of p16INK4a and p15INK4b protein were not changed. It can be concluded that NS-398 enhances the efficacy of gemcitabine against lung adenocarcinoma and the efficacy is associated with up-regulation of p21WAF1 and p27KIP1protein.
 ...
PMID:NS-398 enhances the efficacy of gemcitabine against lung adenocarcinoma through up-regulation of p21WAF1 and p27KIP1 protein. 1834 52

The antisense oligonucleotide 2'-O-methyl-RNA is a selective telomerase inhibitor targeting the telomerase RNA component and represents a potential candidate for anticancer therapy. The poor cellular uptake of 2'-O-methyl-RNA is a limiting factor that may contribute to the lack of functional efficacy. To improve delivery of 2'-O-methyl-RNA and consequently antitumoral efficiency in human lung cancer cells, we have investigated several transfection reagents. The transfection reagents DOTAP, MegaFectin 60, SuperFect, FuGENE 6 and MATra-A were tested for intracellular delivery. A FAM-labeled 2'-O-methyl-RNA was used to assess the intracellular distribution by confocal laser scanning microscopy in A549 human non-small cell lung cancer cells. Telomerase activity was measured using the telomeric repeat amplification protocol. Cell viability after transfection was quantified by the MTT assay. All transfection reagents enhanced 2'-O-methyl-RNA uptake in A549 cells but the cationic lipid reagents DOTAP and MegaFectin 60 were most efficient in the delivery of 2'-O-methyl-RNA resulting in telomerase inhibition. Among both DOTAP exhibited the lowest cytotoxicity. Our experiments show that DOTAP is the most suitable transfection reagent for the delivery of 2'-O-methyl-RNA in human lung cancer cells according to its relatively low cytotoxicity and its ability to promote efficient uptake leading to the inhibition of telomerase.
 ...
PMID:Efficient telomerase inhibition in human non-small cell lung cancer cells by liposomal delivery of 2'-O-methyl-RNA. 1880 62

Pyrogallol, a catechin compound, is an active component of Emblica officinalis extracts and has an anti-proliferative effect on some human cancer cell lines. In our preliminary study, pyrogallol had highly cytotoxic effect on human lung cancer cell lines and less effect on human bronchial epithelium cell line. This study was performed to investigate the beneficial effect of pyrogallol on human lung cancer cell lines - H441 (lung adenocarcinoma) and H520 (lung squamous cell carcinoma). The MTT (cytotoxic) data showed the inhibition growth of lung cancer cells followed pyrogallol treatment. The cell cycle of lung cancer cells was arrested in G2/M phase using flow cytometry. Using Western blot analysis, the cell cycle related proteins - cyclin B1 and Cdc25c were decreased in a time-dependent manner and the phosphorylated Cdc2 (Thr14) was increased within 4h pyrogallol treatment. Moreover, the higher cleavage of poly (ADP)-ribose polymerase (PARP), the increased of Bax concurrent with the decreased of Bcl-2 indicated that pyrogallol treatment resulted in apoptosis of lung cancer cells. The cell apoptosis was also directly demonstrated using Annexin V-FITC and TUNEL stain. Additionally, the tumoricidal effect of pyrogallol was measured using a xenograft nude mice model. After 5 weeks of pyrogallol treatment could cause the regression of tumor. Taken in vitro and in vivo studies together, these results suggest that pyrogallol can be developed as a promising anti-lung cancer drug particular for the non-small cell lung cancer (NSCLC).
 ...
PMID:Pyrogallol induces G2-M arrest in human lung cancer cells and inhibits tumor growth in an animal model. 1923 5

Tumor cells that have acquired resistance to gefitinib may complicate the future treatment of patients with non-small cell lung cancer (NSCLC). To investigate the mechanisms of acquired resistance, an acquired gefitinib-resistant cell line, PC-9/ZD2001, has been established using a gefitinib-sensitive NSCLC cell line, PC-9. PC-9/ZD2001 showed collateral sensitivity to tumor necrosis factor (TNF)-alpha. Bortezomib is a proteasome inhibitor and enhances TNF-alpha-induced cell death. These observations suggest that the combination of bortezomib and TNF-alpha might have effects against gefitinib-resistant cells. To verify this hypothesis, a combination effect between these drugs was examined using MTT assay and immunoblotting. This combination showed synergistic cytotoxic effect in NSCLC cell lines with either acquired or intrinsic gefitinib resistance. However, this combination effect was not observed in gefitinib-sensitive cells. On the other hand, bortezomib inhibited TNF-alpha-induced IkappaB degradation in all cell lines. From these observations, it is concluded that the combination of bortezomib and TNF-alpha could be used to overcome gefitinib-resistance.
 ...
PMID:Combination effect between bortezomib and tumor necrosis factor alpha on gefitinib-resistant non-small cell lung cancer cell lines. 1952 97

We observed a 53% response rate in non-small cell lung cancer (NSCLC) patients treated with vorinostat plus paclitaxel/carboplatin in a Phase I trial. Studies were undertaken to investigate the mechanism (s) underlying this activity. Growth inhibition was assessed in NSCLC cells by MTT assay after 72 hr of continuous drug exposure. Vorinostat (1 microM) inhibited growth by: 17% +/- 7% in A549, 28% +/- 6% in 128-88T, 39% +/- 8% in Calu1 and 41% +/- 7% in 201T cells. Vorinostat addition to carboplatin or paclitaxel led to significantly greater growth inhibition than chemotherapy alone in all 4 cell lines. Vorinostat (1 microM) synergistically increased the growth inhibitory effects of carboplatin/paclitaxel in 128-88T cells. When colony formation was measured after drug withdrawal, vorinostat significantly increased the effects of carboplatin but not paclitaxel. The % colony formation was control 100%; 1 microM vorinostat, 83% +/- 10%; 5 microM carboplatin, 41% +/- 11%; carboplatin/vorinostat, 8% +/- 4%; 2 nM paclitaxel, 53% +/- 11%; paclitaxel/vorinostat, 46% +/- 21%. In A549 and 128-88T, vorinostat potentiated carboplatin induction of gamma-H2AX (a DNA damage marker) and increased alpha-tubulin acetylation (a marker for stabilized mictrotubules). In A549, combination of vorinostat with paclitaxel resulted in a synergistic increase in alpha-tubulin acetylation, which reversed upon drug washout. We conclude that vorinostat interacts favorably with carboplatin and paclitaxel in NSCLC cells, which may explain the provocative response observed in our clinical trial. This likely involves a vorinostat-mediated irreversible increase in DNA damage in the case of carboplatin and a reversible increase in microtubule stability in the case of paclitaxel.
 ...
PMID:Vorinostat increases carboplatin and paclitaxel activity in non-small-cell lung cancer cells. 1962 89

The effects of dithiolethione modified valproate, diclofenac and sulindac on non-small cell lung cancer (NSCLC) cells were investigated. Sulfur(S)-valproate and S-diclofenac at 1 microg/ml concentrations significantly reduced prostaglandin (PG)E(2) levels in NSCLC cell lines A549 and NCI-H1299 as did the COX-2 inhibitor DuP-697. In vitro, S-valproate, S-diclofenac and S-sulindac half-maximally inhibited the clonal growth of NCI-H1299 cells at 6, 6 and 15 microg/ml, respectively. Using the MTT assay, 10 microg/ml S-valproate, NO-aspirin and Cay10404, a selective COX-2 inhibitor, but not SC-560, a selective COX-1 inhibitor, inhibited the growth of A549 cells. In vivo, 18mg/kg i.p. of S-valproate and S-diclofenac, but not S-sulindac, significantly inhibited A549 or NCI-H1299 xenograft proliferation in nude mice, but had no effect on the nude mouse body weight. The mechanism by which S-valproate and S-diclofenac inhibited the growth of NSCLC cells was investigated. Nitric oxide-aspirin but not S-valproate caused apoptosis of NSCLC cells. By Western blot, S-valproate and S-diclofenac increased E-cadherin but reduced vimentin and ZEB1 (a transcriptional suppressor of E-cadherin) protein expression in NSCLC cells. Because S-valproate and S-diclofenac inhibit the growth of NSCLC cells and reduce PGE(2) levels, they may prove beneficial in the chemoprevention and/or therapy of NSCLC.
 ...
PMID:Dithiolethione modified valproate and diclofenac increase E-cadherin expression and decrease proliferation of non-small cell lung cancer cells. 1962 93

1. Erlotinib, a small-molecule epidermal growth factor receptor-tyrosine kinase (EGFR-TK) inhibitor, has been approved for the management of advanced non-small cell lung cancer. The aim of the present study was to investigate whether erlotinib exerts potent antitumour activities through the reactive oxygen species (ROS)-c-Jun N-terminal kinase (JNK) pathway in the human non-small cell lung cancer cell line A549. 2. The 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and Hoechst 33342 staining showed that erlotinib produced a decline in cell viability of A549 cells and induced cell apoptosis, coupled with quick accumulation of ROS. In addition, erlotinib increased the respiratory control ratio, NADPH oxidase catalytic subunit gp91(phox) expression and superoxide anion (O2(-)) generation, suggesting that erlotinib induced ROS production in A549 cells from both mitochondrial and NADPH oxidase sources. 3. Fluorescence microscopy with the JC-1 probe and western blot analysis indicated that erlotinib induced loss of mitochondrial membrane potential, the release of cytochrome c and apoptosis-inducing factor (AIF) and activation of JNK. 4. The results of the present study suggest that erlotinib has potent antitumour activity in A549 cells by activating ROS-dependent, JNK-driven cell apoptosis. These findings provide a novel insight into the mechanism of action of erlotinib in the treatment of human non-small cell lung cancer in addition to its effects in inhibiting EGFR-TK.
 ...
PMID:Erlotinib activates mitochondrial death pathways related to the production of reactive oxygen species in the human non-small cell lung cancer cell line A549. 1967 30


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>