Synthesis and comparison of the antitumor activities of steroids on ABCB1-transfected mouse lymphoma and human ovary carcinoma

Julianna Serly, Irén Vincze, Csaba Somlai, László Hodoniczki, József Molnár

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Multidrug resistance modifiers were indentified against ABC transporters such as ABCB1, but there are other resistance mechanisms based upon such transporters as CTR1 or ATP7A/B membrane proteins. Cisplatin resistance due to the lower expression of CTR1 or to the over-expression of ATP7A/B is also responsible for therapeutic failures in many cancer types. Materials and Methods: 35 modified steroid derivatives were tested for their multidrug reversal and proliferation inhibitory activity comparing their effects in human ABCB1-transfected mouse T-cell lymphoma and cisplatin resistant human ovary carcinoma cell lines. The selected potent resistance reversal agents were tested in a checkerboard assay in the presence of the anticancer drug doxorubicin on mouse lymphoma or cisplatin on human ovary cancer cell lines. Results: Correlations between chemical structure of different steroidal compounds on their effects on drug resistance were investigated. A common characteristic feature of D-ring substituents with N or O atom in the position of 1,3 was found within the effective inhibitors of proliferation when comparing the effective compounds on the two cancer cell lines. Conclusion: We assume that the polar substituents forming a bidentate part may serve as a binding moiety on the polar protein-glycan surface of the cells and can result in an effect independent of the structure of the A ring.

Original languageEnglish
Pages (from-to)138-147
Number of pages10
JournalLetters in Drug Design and Discovery
Volume8
Issue number2
DOIs
Publication statusPublished - Feb 1 2011

Keywords

  • ABCB1
  • Cisplatin resistance
  • Human ovary carcinoma cell line
  • Modified steroids
  • Mouse T-cell lymphoma cell line
  • Multidrug resistance

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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