Metabolic alterations in K562 cells exposed to taxol and tyrphostin AG957: 1H NMR and biochemical studies.
K562 cells exposed for 3 h to taxol or taxol plus tyrphostin AG957 exhibited a significant variation in the concentration of the water-soluble metabolites glutathione, myo-inositol and phosphorylcholine, as evaluated by (1)H NMR up to 72 h incubation in drug-free medium. Cells treated with both drugs showed an increase of glutathione and glutathione reductase at 24 h and a sharp decrease of myo-inositol between 8 and 24 h. Phosphorylcholine increased at 8 h both in taxol and taxol plus AG957-treated cells, which was then abruptly inverted to a significantly lower concentration at 24 h, subsequently increasing again to values higher than those found in taxol-treated and control cells. All the above reported effects were lacking in cells exposed to AG957 alone. These modifications, despite the enhancement of the overall apoptotic cascade in taxol plus AG957-treated cells, can be related to the activation of cellular detoxification mechanisms, to the correct osmolarity maintenance, and to alterations of phospholipid metabolism.
Knijn
Arno
A
Data Management Service, Istituto Superiore di Sanità, 00161 Rome, Italy.
Brisdelli
Fabrizia
F
Ferretti
Amalia
A
Iorio
Egidio
E
Marcheggiani
Donatella
D
Bozzi
Argante
A
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D019328:Buthionine Sulfoximine / Q000737:chemistry; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007294:Inositol / Q000737:chemistry / Q000378:metabolism; D020014:K562 Cells; D050356:Lipid Metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D015233:Models, Statistical; D017239:Paclitaxel / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D010767:Phosphorylcholine / Q000737:chemistry; D013997:Time Factors; D020032:Tyrphostins / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D010743:Phospholipids; D020032:Tyrphostins; C104965:tyrphostin AG957; D010767:Phosphorylcholine; D007294:Inositol; D019328:Buthionine Sulfoximine; D005978:Glutathione; D017239:Paclitaxel