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Highest Cytotoxic Activity (highest + cytotoxic_activity)
Selected AbstractsCytotoxicity of settling particulate matter and sediments of the Neckar River (Germany) during a winter floodENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2000Henner Hollert Abstract To investigate the cytotoxic and genotoxic potentials of settling particulate matter (SPM) carried by the Neckar River, a well-studied model for a lock-regulated river in central Europe, during a flood, acute cytotoxicity was investigated using the fibroblast-like fish cell line RTG-2 with the neutral red retention, the succinic acid dehydrogenase (MTT), and the lactatedehydro-genase (LDH) release assays as well as microscopic inspection as endpoints. Genotoxicity of water, pore water, sediments, and SPM were assessed using the Ames test. Different extraction methods (Soxhlet extraction with solvents of variable polarity as well as a fluid/fluid extraction according to pH) in addition to a supplementation of biotests with S9 fractions from the liver of ,-naphthoflavone/phenobarbital-induced rats allowed a further characterization of the biological damage. Both sediments and SPM extracts caused cytotoxic effects in RTG-2 cells. Cytotoxicity was found to increase significantly with polarity of extracting solvents (NR50 = effective concentration for 50% cell death in the neutral red test: 80 [65], 100 [70], 180 [220], and 225 [270] mg/ml for ethanol, acetone, dichloromethane, and n -hexane extracts, respectively, if measured with [without] S9 supplementation). Following extraction according to pH, cytotoxicity could be attributed mainly to neutral substances (NR50: 80 and 218 mg dry SPM/ml test medium for the neutral and the acid fractions, respectively), whereas the slightly acid and basic fractions already showed little or no cytotoxicity. Samples taken during the period of flood rise showed the highest cytotoxic activities. Cytotoxicity was significantly enhanced by the addition of S9 preparations. In contrast, no genotoxic activity was found in native surface waters, pore waters, and SPM. [source] Significant cytotoxic activity in vitro of the EGFR tyrosine kinase inhibitor gefitinib in acute myeloblastic leukaemiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2008Elin Lindhagen Abstract Objectives:, Gefitinib inhibits epidermal growth factor receptor (EGFR) signalling, but may also act by non-EGFR dependent mechanisms. We have investigated the activity of gefitinib in haematological tumour cells, in particular acute myeloblastic leukaemia (AML). Methods:, Cytotoxic activity of gefitinib, alone or in combination with standard anti-leukaemic drugs, was assessed by the short-term fluorometric microculture cytotoxicity assay in tumour cells from 117 patients representing five haematological and five non-haematological malignancies. In AML, the EGFR status was analysed by immunochemistry. Gefitinib-induced apoptosis was investigated in a subset of AML samples, as well as in the leukaemia cell line MV-4-11, using a multiparametric high content screening assay. To confirm activation of caspase-3 in cells treated with gefitinib, a blocking test was carried out in which MV4-11 cells were pretreated with the specific caspase inhibitor DEVD-FMK. Results:, Gefitinib showed highest cytotoxic activity in AML (n = 19) with many samples being sensitive at concentrations achievable in clinical practice (<10 ,M), and no difference between previously untreated and relapsed patients. No correlation between the activity of gefitinib and standard antileukaemic drugs (cytarabine, doxorubicin, etoposide) was observed. Combining gefitinib with these drugs resulted in mainly additive or synergistic (etoposide) effects, with no evidence of sequence dependency. The AML cells did not express the EGFR. Gefitinib induced apoptosis, which was at least partly mediated by activation of the caspase-3 pathway. Conclusion:,In vitro, gefitinib has significant cytotoxic activity in AML by inducing apoptosis through non-EGFR dependent pathways. [source] Synthesis and Structure-Activity Relationship Studies of Pyrazole-based Heterocycles as Antitumor AgentsARCHIV DER PHARMAZIE, Issue 7 2010Ahmad M. Farag Abstract Several 4-cyano-1,5-diphenylpyrazoles attached to different heterocyclic ring systems at position 3 were synthesized starting from ethyl 4-cyano-1,5-diphenyl-1H -pyrazole-3-carboxylate 1. The newly synthesized compounds were tested in vivo for their anti-estrogenic effects and evaluated in vitro for their cytotoxic properties against estrogen-dependent tumors. 3-(5-Mercapto-1,3,4-oxadiazole-2-yl)-1,5-diphenyl-1H -pyrazole-4-carbonitrile 13 revealed the highest cytotoxic activity with a GI50 value equal to 40 nM against the IGROVI ovarian tumor cell line. It also showed an anti-estrogen activity 1.6 more effective than the reference drug, in addition to a high tolerable dose. 3-(5-(Methylthio)-4-phenyl-4H -1,2,4-triazol-3-yl)-1,5-diphenyl-1H -pyrazole-4-carbonitrile 7 was found to have the highest anti-estrogenic activity, while 1,5-diphenyl-3-[5-(phenylamino)-1,3,4-thiadiazol-2-yl]-1H -pyrazole-4-carbonitrile 11 showed the lowest activity. The oral LD50 values revealed that most of the tested compounds are relatively nontoxic. [source] Antiproliferative effects of essential oils and their major constituents in human renal adenocarcinoma and amelanotic melanoma cellsCELL PROLIFERATION, Issue 6 2008M. R. Loizzo Materials and methods: Essential oils were obtained by hydrodistillation and were analysed by gas chromatography and gas chromatography coupled to mass spectrometry. Antiproliferative activity was tested on amelanotic melanoma C32 cells and on renal cell adenocarcinoma cells, using the sulphorhodamine B assay. Results: Cupressus sempervirens ssp. pyramidalis leaf oil exerted the highest cytotoxic activity with an IC50 value of 104.90 µg/mL against C32, followed by activity of P. orientalis and P. asperula on the renal adenocarcinoma cell line (IC50 of 121.93 and 139.17 µg/mL, respectively). P. orientalis essential oil was also active against amelanotic melanoma with an IC50 of 330.04 µg/mL. Three identified terpenes, linalool, ,-caryophyllene and ,-cedrol, were found to be active on both cell lines tested. Conclusions: Our findings provide novel insights into the field of cytotoxic properties of essential oils. This study provided evidence on how cytotoxic activity of the oils is not always related to their major constituents, except for lower activity found in both cell lines for ,-cedrol. Interestingly, ,-caryophyllene and linalool exhibited comparable IC50 values to the commercial drug vinblastine on the ACHN cell line. This opens a new field of investigation to discover mechanisms responsible for the observed activity. [source] | ||||||||||