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• W1991618461 abstract "Hexadecylphosphocholine (HePC, Miltefosine) is a representative of the group of alkyl-lysophosphocholines showing remarkable antitumoral activity in in vitro experiments and in experimental animal tumour models. The epidermoid tumour cell line KB, which is highly sensitive to HePC (half-maximal growth inhibiting concentration, ic 50: 1.2 μM; half lethal concentration, lc 50: 2.8 μM), was slowly adapted to increasing concentrations of HePC. After 14 months, the adaptation process was stopped at a concentration of 10 μg/ml (23.5 μM). At this point, the KB cells tolerated high doses of HePC ( ic 50: 41.2 μM; lc 50: 87.1 μM). The resistant cells (KBr) also showed crossresistance to the other well studied ether-lysophospholipids, Edexfosine ( 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine, OMG-3PC; ET18OCH3) and Ilmofosine (1 S-hexadecyl-2-methoxymethyl-rac-(1-thio-3-hydroxy)propyl-3-phosphocholine, BM 41.440). Comparison of the KB and KBr cells showed that total lipid phosphate, ether-lipid content, vinyl-ether-lipid content, protein content as well as cholesterol content were unchanged. Furthermore, no changes were observed in the lipid composition between KB and KBr cells. Uptake of choline was also unchanged in both cells, but the uptake of d-myo-inositol was lower by a factor of two in the KBr cells. However, in KB cells, the addition of HePC induced a 50% reduction of d-myo-inositol-uptake, whereas in KBr cells inositol uptake was unchanged. Differences in HePC uptake and HePC metabolism were apparent between the KB and KBr cell lines. KBr cells showed a 3-fold lower uptake for HePC and a 3- to 4-fold faster metabolism of HePC than KB cells. However, the amount of non-metabolised HePC after 2 days of incubation with 1 μg/ml HePC ( lc 50: 1.2 μg/ml) in KB cells was 3- to 4-fold lower than the amount of HePC in KBR cells at 10 μg/ml ( lc50: 37 μg/ml), indicating that KBr cells can incorporate higher amounts of HePC than KB cells without adverse effects for cell growth and viability. This seems to indicate that mechanisms other than slower uptake and faster metabolism are involved in the induction of resistance to HePC in KBr cells." @default.
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• W1991618461 date "1996-03-01" @default.
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• W1991618461 title "Induction of resistance to hexadecylphosphocholine in the highly sensitive human epidermoid tumour cell line KB" @default.
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• W1991618461 doi "https://doi.org/10.1016/0959-8049(95)00566-8" @default.
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