Characterization of Cellular Lipids in Doxorubicin-sensitive and -resistant P388 Mouse Leukemia Cells

Overview

Journal Cancer Chemother Pharmacol

Specialty Oncology

Date 1986 Jan 1

PMID 3698172

Citations 4

Authors

W M Holleran

M W DeGregorio

R Ganapathi

J R WILBUR

B A Macher

Affiliations

Soon will be listed here.

Abstract

The purpose of this study was to determine whether changes in cellular lipid composition accompanied the selection of cells that are resistant to the anthracycline doxorubicin. Total cellular lipid extracts from doxorubicin-sensitive and doxorubicin-resistant P388 murine leukemia cells were prepared and separated into neutral glycosphingolipids, gangliosides, phospholipids, and neutral lipid families. No significant quantitative differences in total cholesterol, lipid-bound sialic acid, neutral hexose, and lipid-bound phosphate were found between the two cell lines. Gas-liquid chromatographic analysis of the fatty acids derived from each lipid class demonstrated that sensitive and resistant cells had essentially identical fatty acid compositions. Qualitative evaluation of the four lipid classes by high-performance thin-layer chromatography revealed only minor differences in lipid composition between the resistant and the sensitive cells. Results from this study indicate that although minor differences between the two cell lines are present, no major cellular lipid differences are evident to account for the marked differences in the cellular pharmacokinetics and cytotoxic effects of doxorubicin between doxorubicin-sensitive and doxorubicin-resistant P388 murine leukemia a cells.

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References

Lane M . Clinical problems of resistance to cancer chemotherapeutic agents. Fed Proc. 1979; 38(1):103-7. View

Debenham P, Kartner N, Siminovitch L, Riordan J, Ling V . DNA-mediated transfer of multiple drug resistance and plasma membrane glycoprotein expression. Mol Cell Biol. 1982; 2(8):881-9. PMC: 369875. DOI: 10.1128/mcb.2.8.881-889.1982. View

Biedler J, Riehm H, Peterson R, Spengler B . Membrane-mediated drug resistance and phenotypic reversion to normal growth behavior of Chinese hamster cells. J Natl Cancer Inst. 1975; 55(3):671-80. DOI: 10.1093/jnci/55.3.671. View

Kessel D, Botterill V, Wodinsky I . Uptake and retention of daunomycin by mouse leukemic cells as factors in drug response. Cancer Res. 1968; 28(5):938-41. View

Inaba M, Kobayashi H, Sakurai Y, Johnson R . Active efflux of daunorubicin and adriamycin in sensitive and resistant sublines of P388 leukemia. Cancer Res. 1979; 39(6 Pt 1):2200-3. View

Ganapathi R, Grabowski D, ROUSE W, Riegler F . Differential effect of the calmodulin inhibitor trifluoperazine on cellular accumulation, retention, and cytotoxicity of anthracyclines in doxorubicin (adriamycin)-resistant P388 mouse leukemia cells. Cancer Res. 1984; 44(11):5056-61. View

Wheeler C, Rader R, Kessel D . Membrane alterations associated with progressive adriamycin resistance. Biochem Pharmacol. 1982; 31(16):2691-3. DOI: 10.1016/0006-2952(82)90723-7. View

Young R, Ozols R, Myers C . The anthracycline antineoplastic drugs. N Engl J Med. 1981; 305(3):139-53. DOI: 10.1056/NEJM198107163050305. View

GAVER R, Sweeley C . METHODS FOR METHANOLYSIS OF SPHINGOLIPIDS AND DIRECT DETERMINATION OF LONG-CHAIN BASES BY GAS CHROMATOGRAPHY. J Am Oil Chem Soc. 1965; 42:294-8. DOI: 10.1007/BF02540132. View

10.

BARTLETT G . Phosphorus assay in column chromatography. J Biol Chem. 1959; 234(3):466-8. View

11.

Siegfried J, Kennedy K, Sartorelli A, Tritton T . The role of membranes in the mechanism of action of the antineoplastic agent adriamycin. Spin-labeling studies with chronically hypoxic and drug-resistant tumor cells. J Biol Chem. 1983; 258(1):339-43. View

12.

Dano K . Active outward transport of daunomycin in resistant Ehrlich ascites tumor cells. Biochim Biophys Acta. 1973; 323(3):466-83. DOI: 10.1016/0005-2736(73)90191-0. View

13.

Giavazzi R, Scholar E, Hart I . Isolation and preliminary characterization of an Adriamycin-resistant murine fibrosarcoma cell line. Cancer Res. 1983; 43(5):2216-22. View

14.

Ramu A, Glaubiger D, Weintraub H . Differences in lipid composition of doxorubicin-sensitive and -resistant P388 cells. Cancer Treat Rep. 1984; 68(4):637-41. View

15.

Macher B, Klock J, Fukuda M, Fukuda M . Isolation and structural characterization of human lymphocyte and neutrophil gangliosides. J Biol Chem. 1981; 256(4):1968-74. View

16.

Svennerholm L . Quantitative estimation of sialic acids. II. A colorimetric resorcinol-hydrochloric acid method. Biochim Biophys Acta. 1957; 24(3):604-11. DOI: 10.1016/0006-3002(57)90254-8. View

17.

Lee W, Klock J, Macher B . Isolation and structural characterization of human lymphocyte neutral glycosphingolipids. Biochemistry. 1981; 20(13):3810-4. DOI: 10.1021/bi00516a022. View

18.

Peterson R, MEYERS M, Spengler B, Biedler J . Alteration of plasma membrane glycopeptides and gangliosides of Chinese hamster cells accompanying development of resistance to daunorubicin and vincristine. Cancer Res. 1983; 43(1):222-8. View

19.

Rogers K, Carr B, Tokes Z . Cell surface-mediated cytotoxicity of polymer-bound Adriamycin against drug-resistant hepatocytes. Cancer Res. 1983; 43(6):2741-8. View

20.

Crooke S, DuVernay V, Galvan L, Prestayko A . Structure-activity relationships of anthracyclines relative to effects on macromolecular syntheses. Mol Pharmacol. 1978; 14(2):290-8. View