PSC-833, a frontier in modulation of P-glycoprotein mediated multidrug resistance

Cancer Metastasis Rev. 1998 Jun;17(2):163-8. doi: 10.1023/a:1006046201497.


The expression of drug efflux mechanisms by cancer cells during chemotherapy leads to multidrug resistance (MDR) and constitutes a major obstacle in the effective treatment of cancer. The most widely characterized drug effluxes pump is P-glycoprotein (P-gp) and efforts are being directed towards identifying agents that reverse P-gp mediated drug resistance. PSC-833 is a non-immunosuppressive cyclosporin derivative that potently and specifically inhibits P-gp. The current review focuses on the elucidation of the mechanism of action of PSC-833 as a potential MDR reversing agent, using syngeneic multidrug resistant sublines of MDA435 human breast adenocarcinoma cell line that express increasing levels of P-gp. In vitro experiments indicate that PSC-833 interacts directly with P-gp with high affinity and probably interferes with the ATPase activity of P-gp. Studies in multidrug resistant tumor models confirm P-gp as the in vivo target of PSC-833 and demonstrate the ability of PSC-833 to reverse MDR leukemias and solid tumors in mice. Presently, PSC-833 is being evaluated in the clinic.

Publication types

  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1*
  • Animals
  • Cyclosporins / pharmacology*
  • Cyclosporins / therapeutic use*
  • Drug Resistance, Multiple*
  • Drug Resistance, Neoplasm*
  • Humans
  • Mice
  • Neoplasms / drug therapy*
  • Neoplasms, Experimental / drug therapy
  • Rats


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Cyclosporins
  • valspodar