Lipids: A key role in multidrug resistance? (Review).

  • Authors:
    • J Pallarés-Trujillo
    • F J López-Soriano
    • J M Argilés
  • View Affiliations

  • Published online on: April 1, 2000     https://doi.org/10.3892/ijo.16.4.783
  • Pages: 783-881
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Among tumoral resistances, multidrug resistance (MDR) is characterized as cross-resistance to a variety of structurally and functionally unrelated drugs such as vinca alkaloids, colchicine, and anthracyclines. Decreased drug cellular influx and increased cellular ability for drug extrusion are the main mechanisms involved in MDR. Two plasma membrane proteins, p-glycoprotein (p-gp) and the multidrug resistance-associated protein (MRP), act as ATP-dependent cellular efflux. Furthermore, protein kinase C (PKC) is also central to MDR. The present study reviews the role of cholesterol and other lipids in the reduction of drug influx and drug binding to cellular membranes. The study also examines the effect of lipid composition on p-gp activity. Concerning the role of PKC in MDR, two phospholipases involved in diacylglycerol (DG) production increase in MDR cells. These are phosphatidylinositol-4, 5-bisphosphate-specific phospholipase C and phosphatidylethanolamine-specific phospholipase D. A positive feedback mechanism for DG production which includes these phospholipases, a phosphatidylcholine-specific phospholipase C and a phosphatidylcholine-specific phospholipase A2 has also been suggested. The hypothesis of exocytic involvement in MDR is reviewed, and some lipid changes found in MDR cells are interpreted according to those fusogenic properties normally involved in exocytic transport. Also, the possible role of lipid mediators, such as phosphatidic acid and platelet-activating factor, is examined.

Related Articles

Journal Cover

April 2000
Volume 16 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Pallarés-Trujillo, J., López-Soriano, F., & Argilés, J. (2000). Lipids: A key role in multidrug resistance? (Review).. International Journal of Oncology, 16, 783-881. https://doi.org/10.3892/ijo.16.4.783
MLA
Pallarés-Trujillo, J., López-Soriano, F., Argilés, J."Lipids: A key role in multidrug resistance? (Review).". International Journal of Oncology 16.4 (2000): 783-881.
Chicago
Pallarés-Trujillo, J., López-Soriano, F., Argilés, J."Lipids: A key role in multidrug resistance? (Review).". International Journal of Oncology 16, no. 4 (2000): 783-881. https://doi.org/10.3892/ijo.16.4.783