Cell suspension cultures of Taxus cuspidata produce taxanes that are released from the outer surface of cells into the culture medium as free and bound alkaloids. Paclitaxel (Taxol (TM)), is an anti-cancer drug in short supply. It has a taxane ring derived from baccatin III and a C-13 phenylisoserine side-chain. This drug is produced over a wide range of gravitational forces. Monoclonal and polyclonal antibodies to paclitaxel, baccatin III, and the C-13 phenylisoserine side chain were combined in multiple-labeling studies to localize taxanes and paclitaxel on cell surfaces or on particles released into the culture medium. Bioreactor vessel design altered the composition of taxanes recovered from cells in simulated microgravity. At 10(-2) and 2x10(-4)g, taxane recovery was reduced but biomass growth and percent paclitaxel was significantly increased. At 1 to 24g, growth was reduced with a significant recovery of total taxanes with low percent paclitaxel. Bound paclitaxel was also localized in endonuclease-rich fragmenting nuclei of individual apoptotic cells. A model is presented comprising TCH (touch) genes encoding enzymes that modify taxane-bearing xylan residues in cell walls, the calcium-sensing of gravitational forces by the cytoplasm, and the predisposition of nuclei to apoptosis. This integrates the adaptive physiological and biochemical responses of drug-producing genomes with gravitational forces.
Taxane recovery from cells of Taxus in micro- and hypergravity
Acta astronautica ; 42 , 8-Jan
1998-01-01
Miscellaneous
No indication
English
Taxane recovery from cells of Taxus in micro- and hypergravity
British Library Conference Proceedings | 1998
|PART 6 -- CELLS AND ANIMALS - Taxane recovery from cells of Taxus in micro- and hypergravity
Online Contents | 1998
|Proliferation of Paramecium tetraurelia under Hypergravity
British Library Conference Proceedings | 2002
|Hypergravity suppresses bone resorption in ovariectomized rats
Online Contents | 2011
|Hypergravity modulates cyclic GMP efflux in nitric oxide-stimulated human melanocytic cells
British Library Conference Proceedings | 2005
|