Function and mechanism of pyronaridine: a new inhibitor of P-glycoprotein-mediated multidrug resistance

Acta Pharmacol Sin. 2002 Jun;23(6):544-50.


Aim: To study the effect and mechanism of pyronaridine (PND) on the reversal of multidrug resistance (MDR) in K562/A02 and MCF7/ADR cell lines with mdr1+.

Methods: MTT assay was used to determine the cells growth inhibition after incubation for 72 h in the presence of doxorubicin (DOX) with or without PND. Intracellular accumulation of DOX was analyzed by spectrofluorometry. P-glycoprotein (P-gp) activity was investigated by measuring the extrusion of the cationic dye rhodamine 123 (Rh123). The apoptosis of cells and mdr1 gene expression were detected using flow cytometry and RTPCR, respectively.

Results: PND slightly inhibited the growth of MDR human leukemia, breast cancer cells, and their parental cell lines. The IC50 of PND were 5.10 - 18.66 micromol/L depending on the kinds of cell lines. PND at low toxic concentrations enhanced antiproliferative effect of DOX on MDR cells and the apoptosis induced by DOX in a concentration-dependent manner. Intracellular accumulation of DOX and Rh123 in MDR cell lines increased after combination with PND. PND did not down-regulate mdr1 gene expression in MDR cell lines K562/A02 and MCF7/ADR.

Conclusion: As the third-generation Pgp inhibitor, PND significantly reversed MDR in MDR cell lines K562/A02 and MCF7/ADR by inhibiting P-gp function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors*
  • Antineoplastic Agents / pharmacology
  • Apoptosis
  • Breast Neoplasms / pathology
  • Doxorubicin / pharmacokinetics
  • Doxorubicin / pharmacology
  • Drug Resistance, Multiple*
  • Drug Synergism
  • Female
  • Genes, MDR / genetics*
  • Humans
  • K562 Cells
  • Naphthyridines / pharmacology*
  • Tumor Cells, Cultured


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • Naphthyridines
  • Doxorubicin
  • pyronaridine