Effects of miltefosine on various biochemical parameters in a panel of tumor cell lines with different sensitivities

Citation
M. Rybczynska et al., Effects of miltefosine on various biochemical parameters in a panel of tumor cell lines with different sensitivities, BIOCH PHARM, 62(6), 2001, pp. 765-772
Citations number
45
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BIOCHEMICAL PHARMACOLOGY
ISSN journal
0006-2952 → ACNP
Volume
62
Issue
6
Year of publication
2001
Pages
765 - 772
Database
ISI
SICI code
0006-2952(20010915)62:6<765:EOMOVB>2.0.ZU;2-0
Abstract
We investigated endocytosis activity, uptake of miltefosine (hexadecylphosp hocholine), phospholipid and cholesterol content, the cell cycle, and apopt osis in 13 tumor cell lines (MCF7, MCF7/ADR, KB-3-1, KB-8-5, KB-Cl, HeLa, H eLa-MDR1-G185, HeLa-MDR1-V185, CCRF/CEM, CCRF/VCR 1000, CCRF/ADR5000, HL-60 , HL-60/AR) with different sensitivities to treatment with the antitumor ph ospholipid analogues miltefosine and D-21266 (octadecyl-(N,N-dimethyl-piper idino-4-yl)-phosphate). In this panel of cell lines, MDR1 (multidrug resist ance gene 1)- and MRP1 (multidrug resistance-associated protein)-expressing cells were found to be slightly more resistant to both compounds than sens itive parental cells. No correlation was found between resistance to miltef osine and endocytosis, intracellular concentration of miltefosine, the phos pholipid and cholesterol content, induction of apoptosis, or cell cycle alt erations in all the cell lines tested. Wild-type p53 containing WMN Burkitt 's lymphoma cells and wild type p53-deficient CA46 exhibited similar sensit ivities to miltefosine. The low percentage of apoptosis induced in MCF7 cel ls lacking caspase 3 indicated that caspase 3 seems to play an essential ro le in miltefosine-induced apoptosis. (C) 2001 Elsevier Science Inc. All rig hts reserved.