Plasma membrane lipid composition of vinblastine sensitive and resistant human leukaemic lymphoblasts

Abstract

Plasma membranes purified 32- to 45-fold were isolated from leukaemic T-lymphoblasts, both sensitive and resistant to the Vinca alkaloid vinblastine. On development of drug resistance there was a very significant elevation of ether lipid content. 1-0-alkyl phospholipid increased by 200% with a smaller 30% increase in 1-0-alkenyl phospholipid. Cholesterol and phospholipid levels were also found to increase by 50% and 30% respectively, while the lipid to protein ratio increased by 60%. More modest changes were observed in the fatty acid composition of the membranes, with an alteration in the double bond index from 35.3 to 41.2. These lipid changes may have important implications in the changes to membrane permeability that develop with drug resistance.

The plant alkaloid voacamine induces apoptosis-independent autophagic cell death on both sensitive and multidrug resistant human osteosarcoma cells

“…For instance, in vinblastine-resistant leukemic lymphoblasts, cholesterol and phospholipids levels were found to increase by 50% and 30% respectively, while the lipid to protein ratio increased by 60%. 36 The analysis by freeze-fracture electron microscopy, besides confirming the remarkable increase of vesicular structures inside VOA-treated cells, furnished further ultrastructural details on the autophagosome formation and on their structural differences between sensitive and resistant cells. The freeze-fracture images have to be interpreted on the basis of the various models proposed for the autophagosome formation.…”

Increased sensitivity of multidrug-resistant myeloid leukemia cell lines to lovastatin

“…15 Of note, cholesterol level was found to increase by as much as 50% in some multidrug resistant cells in comparison with their parental cells. 42,43 Present study showed that Pgp-expressing leukemia cell lines K-562/ADR, NOMO-1/ADR and NB4/RA/MDR were more sensitive to lovastatin than their parental cell lines in terms of inhibition of proliferation and induction of apoptosis. However, despite the high expression of MDR-1 mRNA and Pgp on membrane, the MDR-1 genetransduced variant of NB4, NB4/MDR, was not more sensitive to lovastatin, showing equal sensitivity to lovastatin as their parental cells.…”

Agents that Reverse Multidrug Resistance, Tamoxifen, Verapamil, and Cyclosporin A, Block Glycosphingolipid Metabolism by Inhibiting Ceramide Glycosylation in Human Cancer Cells

“…Reports show that P-gp ATPase activity is dependent on the lipid environment (5), and lipids interact with P-gp substrates (6). Differences in glycerolipid and sphingomyelin compositions of multidrug-resistant and drug-sensitive cells have been reported (7)(8)(9)(10)(11), and ganglioside composition of multidrug-resistant and drug-sensitive cells has been examined. Whereas diversity in ganglioside composition was revealed, no definitive correlation with drug resistance was demonstrated (7,12).…”