MAPK inhibitors augment gallic acid-induced A549 lung cancer cell death through the enhancement of glutathione depletion.
Woo Hyun Park, Suhn Hee Kim
(Department of Physiology, Medical School, Research Institute for Endocrine Sciences, Chonbuk National University, Jeonju 561-180, Republic of Korea. parkwh71@chonbuk.ac.kr)
Oncol. Rep.
gallic_acid ga is involved in various biological_processes such_as cell growth_inhibition and apoptosis through changes in reactive_oxygen species_ros in the present_study we_investigated the effects of mapk mek jnk or p38 inhibitors on cell death in ga-induced a549 lung cancer cells in relation to ros and glutathione_gsh treatment with μm ga inhibited the growth of a549_cells and induced_apoptosis and/or necrosis which was accompanied_by the loss of mitochondrial_membrane potential_mmp ∆ψ ga increased ros levels as_well as gsh_depletion in a549_cells at mek_inhibitor seemed to enhance cell growth_inhibition by ga this inhibitor also increased cell death mmp ∆ψ loss and gsh_depletion in ga-treated a549_cells both jnk and p38 inhibitors intensified growth_inhibition cell death mmp ∆ψ loss and gsh_depletion by ga however none of the mapk_inhibitors significantly altered ros levels in ga-treated a549_cells in conclusion mapk_inhibitors enhanced growth_inhibition and death in ga-treated a549_cells which were correlated with gsh_depletion rather_than ros levels
Prevention of mouse lung tumors and modulation of DNA methylation by combined treatment with budesonide and R115777 (Zarnestra MT).
Fadel S Alyaqoub, Lianhui Tao, Paula M Kramer, Vernon E Steele, Ronald A Lubet, William T Gunning, Michael A Pereira
(Medical University of Ohio, Toledo, OH 43614, USA.)
Carcinogenesis
budesonide an anti-inflammatory glucocorticoid r115777 farnesyl_transferase inhibitor zarnestra tipifarnib or combinations of them were evaluated for prevention of lung tumors and for modulation of dna_methylation in tumors lung tumors were induced by vinyl_carbamate in female_strain mice one week_later mice received or mg/kg_r115777 by oral_gavage and days/week or mg/kg of budesonide in their diet or their combined treatment until_killed at and weeks after administering the vinyl_carbamate other mice were administered the drugs for weeks before killing at week at week the rank_order for prevention of lung tumors was the combined treatment budesonide r115777 at later killings r115777 was no longer effective whereas budesonide and the combinations continued to prevent tumors albeit at reduced efficacy dna_hypomethylation in lung tumors was prevented by treatment with r115777 budesonide and the combinations when administered starting at week to tumor-bearing_mice the drugs reversed dna_hypomethylation in the tumors in summary combined treatment with budesonide and r115777 produced the following results it was more_efficacious in preventing lung tumors than the individual drugs and ii it prevented and reversed dna_hypomethylation in lung tumors these_results support the combined use of budesonide and r115777 in prevention of lung tumors and suggest_that reversal of dna_hypomethylation in lung tumors would_be useful as_surrogate end-point biomarker for
Decoding circulating nucleic acids in human serum using microfluidic single molecule spectroscopy.
Kelvin J Liu, Malcolm V Brock, Ie-Ming Shih, Tza-Huei Wang
(Biomedical Engineering Department, 3400 North Charles Street, Johns Hopkins University, Baltimore, Maryland 21218, USA.)
J. Am. Chem. Soc.
circulating_nucleic acid cna has_been the focus of recent research as noninvasive source of biomarker_candidates among these markers dna fragment size has shown_promise for discerning the source of cna molecules in cancer and prenatal diagnostics we have developed one-step assay for analyzing circulating_dna size and quantity directly in human serum microfluidic cylindrical illumination confocal spectroscopy and fluorescence burst size analysis are used to individually count and size fluorescently-labeled cna molecules as they are driven through microfluidic constriction first single molecule sizing was performed on lambda hind iii digest dna to obtain size calibration_curve linear relation_between dna length and burst size was seen from bp to kbp subsequently the single molecule assay parameters were optimized finally dna sizing analysis was performed on serum_samples from both early and late stage lung cancer patients this assay was performed directly in patient serum using only single reagent simple dna intercalating dye and without the need for dna isolation or enzymatic amplification steps this demonstrates_that microfluidic single molecule spectroscopy can_be rapid facile and inexpensive alternative to the established pcr-based_methods that have_been used near exclusively for cna
Effects of navelbine and docetaxel on gene expression in lung cancer cell strains.
Li Cai, Hai-ying Dong, Guang-jie Sui
(Internal Medicine of Oncology, the Third Affiliated Hospital of Harbin Medical University, Harbin 150040, China. caiwenxin76@yahoo.com.cn)
Acta Pharmacol. Sin.
to search genes sensitivity to the anti-cancer_drugs navelbine_nvb and docetaxel_doc in small-cell_lung cancer sclc and non-small-cell_lung cancer nsclc cell strains the sensitivity of strains of sclc and strains of nsclc to nvb and doc was evaluated using the mtt_assay the expression of sensitive-related genes to the anti-cancer_drugs in lung cancer cell strains was measured using cdna macroarrays and the relationship was analyzed in total there were or genes sensitive to nvb and doc for nvb genes were sensitive to nvb co-expressed genes between the sclc+nsclc_set and the nsclc set expressed genes and specially_expressed genes in the sclc+nsclc_set and expressed genes and specially_expressed genes in the nsclc set for doc genes were sensitive to doc co-expressed genes between the sclc+nsclc_set and the nsclc set expressed genes and specially_expressed genes in the sclc+nsclc_set and expressed genes and specially_expressed genes in the nsclc set the genes sensitive to nvb and doc in lung-cancer cell stains were mainly divided_into the following categories signal_transduction molecules cell factors transcription_factors and metabolism-related enzymes and inhibitors there were obvious differences in genes related to nvb and doc between sclc and nsclc cell strains but the same as categories
FTY720 treatment in experimentally urethane-induced lung tumors.
Léa Bueno Lucas da Silva, Daniel Araki Ribeiro, Patrícia Maluf Cury, José Antonio Cordeiro, Valquiria Bueno
(Division of Immunology, FAMERP Sao Jose do Rio Preto Medical School, Brazil.)
J. Exp. Ther. Oncol.
fty720 has_been shown to prevent cancer development in experimental_models but there is no report whether this beneficial_effect is associated with the time_point of the drug_administration lung adenoma was induced in mice by urethane_injection followed_by different periods of fty720 administration in order to evaluate lung tumor development balb/c_mice received two doses g/kg of urethane intraperitoneally and were submitted to five daily_doses of fty720 mg/kg/day starting just after urethane_injection g2 weeks after urethane_injection g3 weeks after urethane_injection g4 and no fty720 administration g1 twenty-four weeks after urethane administration mice were evaluated for leukocyte numbers in blood_lymphocytes in spleen and lungs were evaluated for changes in histology and pcna expression lung nodules were present in higher numbers both in non treated g1 0-7 and fty720 treated weeks after urethane_injection g4 0-6 g4 group also presented the highest number of papillary nodules there was decrease in pcna staining in early time fty720 treated mice therefore our_data suggest_that fty720 treatment in early periods after lung tumor induction is beneficial and impairs adenoma development
Stromal cell-derived factor-1 enhances motility and integrin up-regulation through CXCR4, ERK and NF-kappaB-dependent pathway in human lung cancer cells.
Yi-Chia Huang, Yu-Chun Hsiao, Ying-Ju Chen, Ying-Ying Wei, Tzu-Hsu Lai, Chih-Hsin Tang
(School of Cosmeceutics, College of Pharmacy, China Medical University, Taichung, Taiwan.)
Biochem. Pharmacol.
the chemokine stromal-derived factor-1alpha sdf-1alpha and its receptor_cxcr4 play_crucial role in adhesion and migration of human cancer cells integrins are the major adhesive molecules in mammalian cells here_we found that sdf-1alpha increased the migration and cell surface expression of beta1 or beta3_integrin in human lung cancer cells a549_cells cxcr4-neutralizing antibody cxcr4 specific inhibitor amd3100 or small_interfering rna against cxcr4 inhibited the sdf-1alpha-induced increase in the migration of lung cancer cells stimulation of cells with sdf-1alpha caused an increase in extracellular_signal regulated kinase_erk phosphorylation in time-dependent_manner in addition treatment of a549_cells with erk inhibitor_pd98059 nf-kappab inhibitor pdtc or ikappab protease_inhibitor tpck inhibited sdf-1alpha-induced cells migration and integrins expression treatment of a549_cells with sdf-1alpha induced ikappab_kinase alpha/beta ikk alpha/beta phosphorylation ikappabalpha_phosphorylation ikappabalpha degradation p65_ser phosphorylation and kappab-luciferase_activity the sdf-1alpha-mediated increases in ikk alpha/beta phosphorylation p65_ser phosphorylation and kappab-luciferase_activity were inhibited by pd98059 and erk2 mutant taken_together these_results suggest_that sdf-1alpha acts_through cxcr4 to activate erk which in turn_activates ikkalpha/beta and nf-kappab resulting in the activations of beta1 and beta3 integrins and contributing the migration of
Combination therapeutic effect of cisplatin along with Solanum trilobatum on benzo(a)pyrene induced experimental lung carcinogenesis.
P N Venkatesan, P Rajendran, G Ekambaram, D Sakthisekaran
(Department of Medical Biochemistry, Dr ALM PG Institute of Basic Medical Sciences, University of Madras, Chennai, India. pnv76@yahoo.com)
Nat. Prod. Res.
lung cancer is one of the leading_causes of cancer death in the world and is notoriously_difficult to treat effectively in the present_study male_swiss albino_mice were divided_into five groups of six animals each group animals received corn_oil orally and served_as control_group ii cancer-induced animals received benzo_pyrene mg_kg bodyweight dissolved in corn_oil orally_twice weekly for four successive weeks group iii cancer-bearing_animals after weeks of induction were treated with cisplatin mg_kg bodyweight once_weekly for weeks group iv cancer-bearing_animals were treated with cisplatin along with solanum trilobatum mg_kg bodyweight orally_once weekly for weeks and group animals constituted the drug control treated with cisplatin along with trilobatum the serum lung and liver were investigated biochemically for aryl_hydrocarbon hydroxylase gamma-glutamyl_transpeptidase nucleotidase lactate_dehydrogenase ldh and protein-bound carbohydrate components hexose hexosamine and sialic_acid these enzyme_activities were increased significantly in cancer-bearing_animals compared with control_animals the elevation of these in cancer-bearing_animals was indicative of the persistent deteriorating effect of in cancer-bearing_animals our_data suggest_that cisplatin administered with trilobatum may extend its chemotherapeutic effect through modulating protein-bound carbohydrate levels and marker enzymes as they are indicators of cancer the combination of cisplatin with trilobatum could effectively treat the p-induced lung cancer in mice by offering protection from reactive_oxygen species damage
Secretion of metastasis related gangliosides by mouse B16-melanoma in circulation in vivo and in culture media in vitro.
S Saha, K C Mohanty
(Department of Metabolic Regulation, Chittaranjan National Cancer Institute, Kolkata, India. sahasandip51@rediffmail.com)
Indian J. Exp. Biol.
mouse b16luf1 melanoma cells of lower metastatic_potential to lung were treated in vitro with same concentration microm of gangliosides prepared from plasma of mice_bearing lung metastasis of b16luf5_b16luf9 or b16luf10 melanoma cell_lines of increasing metastatic_potential to lung luf1 luf5 luf9 luf10 and injected to normal mice through tail_vein the number of metastatic tumor nodules formed in lung increased gradually in mice receiving b16luf5_b16luf9 and b16luf10-ganglioside-treated b16luf1_cells compared to mice receiving b16luf1_cells without_any ganglioside treatment similarly mouse b16luf1 melanoma cells treated in vitro with microm concentration of gangliosides prepared from spent culture_media of b16luf5_b16luf9 or b16luf10 cells cultured in vitro were injected to normal mice through tail_vein the number of metastatic tumor nodules formed in lung increased gradually in mice receiving b16luf5_b16luf9 and b16luf10-ganglioside-treated b16luf1_cells compared to mice receiving b16luf1_cells without_any ganglioside treatment the results_indicated that metastasis-associated gangliosides present in plasma and culture_media of b16-melanoma of increasing metastatic_potential to lung enhanced metastatic_potential of b16luf1_cells the increasing concentration of metastasis-associated gangliosides present in plasma and in culture_media of b16-melanoma of increasing metastatic_potential possibly
The effects of N-acetyl cysteine, buthionine sulfoximine, diethyldithiocarbamate or 3-amino-1,2,4-triazole on antimycin A-treated Calu-6 lung cells in relation to cell growth, reactive oxygen species and glutathione.
Yong Hwan Han, Woo Hyun Park
(Department of Physiology, Medical School, Institute for Medical Sciences Chonbuk National University, JeonJu 561-180, Korea.)
Oncol. Rep.
antimycin ama_inhibits mitochondrial_electron transport between cytochrome and we recently demonstrated that ama_inhibits the growth of lung cancer calu-6_cells and the changes of reactive_oxygen species_ros and glutathione_gsh levels affect apoptosis in calu-6_cells here_we examined the effects of n-acetyl-cysteine nac well_known antioxidant l-buthionine_sulfoximine bso an inhibitor of gsh_synthesis diethyl-dithiocarbamate ddc an inhibitor of cu_zn-sod or 3-amino-1 4-triazole at an inhibitor of catalase on ama-treated_calu-6 cells in relation to cell death ros and gsh_levels treatment with ama induced cell growth_inhibition apoptosis and the loss of mitochondrial_membrane potential_mmp deltapsim in calu-6_cells while the intracellular_ros level was decreased in microm ama-treated_calu-6 cells o2 levels among ros were significantly increased ama also induced gsh_depletion in calu-6_cells treatment with nac showed decreasing effect on o2 levels in ama-treated cells preventing apoptosis mmp deltapsim loss and gsh_depletion in these cells bso significantly increased gsh_depletion and apoptosis in ama-treated cells while both ddc and at increased ros levels in ama-treated_calu-6 cells only ddc intensified gsh_depletion and apoptosis bso and at increased the ros level in calu-6 control cells but these agents did_not induce_apoptosis and gsh_depletion in conclusion_our results_suggest that gsh_depletion rather_than ros level in ama-treated_calu-6 cells is more
Effects of navelbine and docetaxel on gene expression in human lung cancer cell lines.
Guangyue Shi, Li Cai, Wei Jiang, Guangjie Sui
(Department of Medicine & Oncology, The Third Affiliated Hospital of Harbin Medical University, Harbin 150040, China.)
Cell Biochem. Biophys.
in this_study we identified the genes in small_cell lung cancer sclc and non-small_cell lung cancer nsclc cell_lines sensitive to anticancer_drugs for this purpose sensitivity of four sclc and six nsclc cell_lines to navelbine_nvb and docetaxel_doc was evaluated using mtt_assay expression of `291 drug sensitivity-related genes in these cells was measured by cdna macroarrays and their relationship was analyzed overall there were genes sensitive to nvb and doc regarding nvb genes were sensitive to nvb co-expressed genes between sclc+nsclc and nsclc sets expressed and seven specially_expressed genes in sclc+nsclc_set and expressed and nine specially_expressed genes in nsclc set concerning doc genes were sensitive to doc co-expressed genes between sclc+nsclc and nsclc sets expressed and specially_expressed genes in sclc+nsclc_set and expressed and specially_expressed genes in nsclc set the genes sensitive to nvb and doc in these cell_lines were categorized_into signal_transduction molecules cell factors transcription_factors and metabolism-related enzymes and their inhibitors in conclusion there were gene expression differences_between sclc and nsclc cell_lines related to nvb and doc nevertheless these