Simultaneous combination of microtubule depolymerizing and stabilizing agents acts at low doses. 1995

P Garcia, and D Braguer, and G Carles, and C Briand
URA CNRS 1924, Faculté de Pharmacie, Marseille, France.

The combined activity of a stabilizing and a depolymerizing agent was studied on microtubule formation in vitro and on cellular parameters related to the cytoskeleton. New compounds in each class of microtubular drugs, docetaxel, as stabilizing agent, and CI 980, as colchicine analog, currently in clinical trials, were tested at high and low concentrations. Simultaneous combination of docetaxel and CI 980, both in vitro and in cell lines, induced microtubule structures resulting from the association of the effects of the two drugs: short and numerous microtubules in vitro, abnormal asters or short bundles in cells depolymerized in their periphery. Moreover, combining the two drugs at low concentrations inducing neither modification of the microtubular network nor variation in cell polymerized tubulin content showed synergistic effects in mitotic cell block and, at lower concentrations, in inhibition of proliferation in the KB 3-1 cell line. Similar qualitative results were obtained with paclitaxel and colcemid, used in the place of docetaxel and CI 980, respectively. At low doses, the taxoid/colchine analog combination seems to induce some degree of mitotic inhibition, resulting from a subtle effect on the inhibition of microtubule dynamics.

UI MeSH Term Description Entries
D007624 KB Cells This line KB is now known to be a subline of the ubiquitous KERATIN-forming tumor cell line HeLa. It was originally thought to be derived from an epidermal carcinoma of the mouth, but was subsequently found, based on isoenzyme analysis, HeLa marker chromosomes, and DNA fingerprinting, to have been established via contamination by HELA CELLS. The cells are positive for keratin by immunoperoxidase staining. KB cells have been reported to contain human papillomavirus18 (HPV-18) sequences. HeLa-KB Cells,Cell, HeLa-KB,Cell, KB,Cells, HeLa-KB,Cells, KB,HeLa KB Cells,HeLa-KB Cell,KB Cell
D008856 Microscopy, Fluorescence Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye. Fluorescence Microscopy,Immunofluorescence Microscopy,Microscopy, Immunofluorescence,Fluorescence Microscopies,Immunofluorescence Microscopies,Microscopies, Fluorescence,Microscopies, Immunofluorescence
D008868 Microtubule Proteins Proteins found in the microtubules. Proteins, Microtubule
D008870 Microtubules Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein TUBULIN and are influenced by TUBULIN MODULATORS. Microtubule
D011719 Pyrazines A heterocyclic aromatic organic compound with the chemical formula C4H4N2. Pyrazine
D011725 Pyridines Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
D002219 Carbamates Derivatives of carbamic acid, H2NC( Carbamate,Aminoformic Acids,Carbamic Acids,Acids, Aminoformic,Acids, Carbamic
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D003078 Colchicine A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (PERIODIC DISEASE). Colchicine, (+-)-Isomer,Colchicine, (R)-Isomer
D003703 Demecolcine An alkaloid isolated from Colchicum autumnale L. and used as an antineoplastic. Colcemid,Colcemide,Colchamine,Demecolcine, (+-)-Isomer

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