The relationship between H-1-NMR mobile lipid intensity and cholesterol intwo human tumor multidrug resistant cell lines (MCF-7 and LoVo)

The high resolution proton nuclear magnetic resonance (H-1-NMR) spectra of two different cell lines exhibiting multidrug resistance (MDR) as demonstra ted by the expression of the well-known energy-driven, membrane-bound 170 k Da P-glycoprotein pump known as Pgp were investigated. In particular, the m obile lipid (ML) profile, and the growth and biochemical characteristics of MCF-7 (human mammary carcinoma) and LoVo (human colon adenocarcinoma) sens itive and resistant tumor cells were compared. The results indicate that bo th MCF-7 and LoVo resistant cells have a higher ML intensity than their res pective sensitive counterparts. However, since sensitive and resistant cell s of each pair grow in the same manner, variations in growth characteristic s do not appear to be the cause of the ML changes as has been suggested by other authors in non-resistant tumor cells. In order to investigate further the origin of the ML changes, lipid analyses were conducted in sensitive a nd resistant cell types. The results of these experiments show that resista nt cells of both cell types have a greater amount of esterified cholesterol and saturated cholesteryl ester and triglyceride fatty acid than their sen sitive counterparts. From a thorough analysis of the data obtained in this paper utilizing numerous techniques including biological, biophysical and b iochemical ones, it is hypothesized that cholesterol and triglyceride play a pivotal role in inducing changes in NMR ML signals. The importance of the se lipid variations in MDR is discussed in view of the controversy regardin g the origin of ML signals and the paramount role played by the Pgp pump iq resistance. (C) 2001 Elsevier Science B.V. All rights reserved.