Tryptanthrin inhibits MDR1 and reverses doxorubicin resistance in breast cancer cells

Biochem Biophys Res Commun. 2007 Jun 22;358(1):79-84. doi: 10.1016/j.bbrc.2007.04.107. Epub 2007 Apr 26.


Development of agents to overcome multidrug resistance (MDR) is important in cancer chemotherapy. Up to date, few chemicals have been reported to down-regulate MDR1 gene expression. We evaluated the effect of tryptanthrin on P-glycoprotein (P-gp)-mediated MDR in a breast cancer cell line MCF-7. Tryptanthrin could depress overexpression of MDR1 gene. We observed reduction of P-gp protein in parallel with decreases in mRNA in MCF-7/adr cells treated with tryptanthrin. Tryptanthrin suppressed the activity of MDR1 gene promoter. Tryptanthrin also enhanced interaction of the nuclear proteins with the negatively regulatory CAAT region of MDR1 gene promoter in MCF-7/adr. It might result in suppression of MDR1 gene. In addition, tryptanthrin decreased the amount of mutant p53 protein with decreasing mutant p53 protein stability. It might contribute to negative regulation of MDR1 gene. In conclusion, tryptanthrin exhibited MDR reversing effect by down-regulation of MDR1 gene and might be a new adjuvant agent for chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis
  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms
  • Cell Line, Tumor
  • Doxorubicin / pharmacology*
  • Drug Resistance, Multiple / drug effects
  • Drug Resistance, Neoplasm / drug effects*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mutation
  • Promoter Regions, Genetic
  • Quinazolines / pharmacology*
  • Tumor Suppressor Protein p53 / biosynthesis


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • Quinazolines
  • Tumor Suppressor Protein p53
  • tryptanthrine
  • Doxorubicin