Reversal of multidrug resistance of tumor cells

D. Szabó, H. Keyzer, H. E. Kaiser, J. Molnár

Research output: Contribution to journalReview article

63 Citations (Scopus)


Drug resistance to chemotherapy is rapidly emerging. Resistance to one drug carries over resistance to unrelated anticancer drugs leading to multidrug resistance (MDR). A major factor of MDR is P-glycoprotein (P-gp) mediated ABC transport found in many eukaryotic cells. P-gp acts as a drug eMux pump. The mdr1 gene involved in P-gp 170 protein production is localized in the human chromosome 7 band p2 1.0 - 21.1. Point mutations alter cross-resistance patterns. A variety of stimuli increase the expression of the mdr1 gene: lowered extracellular pH, heat shock, arsenite, cytotoxic agents, anticancer drugs, transfection with oncogenes, HIV-I, and UV-irradiation. An alternative hypothesis to the efflux pump claims that P-gp modifies the intracellular environment to reduce accumulation of anticancer drugs in cancer cells by creating ionic or proton gradients. Chemosensitizers that block P-gp drug extrusion are generally lipid-soluble at physiological pH, possess a basic nitrogen atom and at least two co-planar rings. P-gp blocking does not depend on drug chirality. This opens the way of treating P-gp related MDR with chiral versions of drugs relatively harmless in terms of side-effects. We believe that resistance modifiers combined with cytostatics will chemotherapeutically be more effective for cancer patients.

Original languageEnglish
Pages (from-to)4261-4274
Number of pages14
JournalAnticancer research
Issue number6 B
Publication statusPublished - Dec 1 2000



  • Human mdr1-gene
  • Mouse lymphoma
  • Multidrug resistance reversal
  • Specificity and stereselectivity

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Szabó, D., Keyzer, H., Kaiser, H. E., & Molnár, J. (2000). Reversal of multidrug resistance of tumor cells. Anticancer research, 20(6 B), 4261-4274.