This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kaplan, O. Articles by Cohen, J. S. Search for Related Content PubMed PubMed Citation Articles by Kaplan, O. Articles by Cohen, J. S.

The Multidrug Resistance Phenotype: ³¹P Nuclear Magnetic Resonance Characterization and 2-Deoxyglucose Toxicity

Medicine Branch [O. K., J. W. J., C. R. F., J. S. C.], and Laboratory of Cell Biology [P. S., S. G., M. M. G.], National Cancer Institute, NIH, Bethesda, Maryland 20892, and Lombardi Cancer Research Center, Georgetown University Medical Center, Washington, DC 20007 [R. C.]

In order to identify changes in ³¹P nuclear magnetic resonance (NMR) spectra associated with multiple drug resistance (MDR), a number of wild type and drug-resistant cancer cell lines were studied. The resistant cells included cells selected with various drugs, mainly Adriamycin, as well as cells transfected with the human multidrug resistance gene (MDR1 gene), which encodes P-glycoprotein. In most cases, ³¹P NMR spectra were significantly different from those of parental, drug-sensitive lines. The spectra of resistant cells generally indicated increased levels of ATP and phosphocreatine in the cytoplasm. These changes are compatible with the increased glucose utilization rate previously described for resistant cells. Major changes were also observed in the levels of glycerophosphocholine and glycerophosphoethanolamine. Changes in cellular metabolism reflected by ³¹P NMR spectra depend on the drug used to select the cells for MDR. The direction of these changes was not consistent for all cell lines studied and could not be directly attributed to expression of P-glycoprotein, suggesting that the changes may be related to alterations in metabolism and membrane function associated with other mechanisms of MDR. The results demonstrate the suitability of ³¹P NMR for studies of biochemical changes associated with MDR. The toxicity of 2-deoxyglucose, a glucose antimetabolite, was investigated in addition to the NMR studies and was found to be consistently higher in multidrug-resistant cells than in the parental drug-sensitive lines. For MCF-7 breast cancer cells, where several sublines with different levels of resistance were available, the toxicity was highest for the most resistant lines.

¹ Permanent address: Department of Organic Chemistry and PharmaBiotec Research Center, Royal Danish School of Pharmacy, Universitetsparken 2, DK-2100 Copenhagen, Denmark. Financial support from the Alfred Benzon Foundation, NATO Science Fellowships Programme, and Danish Medical Research Council to J. W. J. is gratefully acknowledged.

² Present address: Bristol-Myers Squibb Company, Experimental Therapeutics, 5 Research Parkway, Wallingford, CT 06492.

³ Present address: Department of Pharmacology, Georgetown University, Georgetown Laboratories, 4 Research Court, Rockville, MD 20850.

Received 8/30/90. Accepted 1/ 8/91.

This article has been cited by other articles:

				N. Maril, H. Degani, E. Rushkin, A. D. Sherry, and M. Cohn Kinetics of cyclocreatine and Na+ cotransport in human breast cancer cells: mechanism of activity Am J Physiol Cell Physiol, October 1, 1999; 277(4): C708 - C716. [Abstract] [Full Text] [PDF]