Substituted steroidal compounds containing amino and amido groups reverse multidrug resistance of mouse T-lymphoma and two human prostate cancer cell lines In Vitro

Ákos Csonka, Sami Hamdoun, Gabriella Spengler, Ana Martins, Irén Vincze, Thomas Efferth, Joseph Molnár

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Resistance to chemotherapy is a main problem in cancer. The search for new effective compounds that can increase sensitivity of resistant cells to existing chemotherapeutics is an urgent need. In previous studies, it has been demonstrated that steroid derivatives showed promising results concerning their capacity to modulate resistance of multidrug-resistant cell lines. Materials and Methods: Steroid derivatives were studied for their growth-inhibitory effect, cytotoxicity, reversal of multidrug resistance, apoptosis induction, and interaction with doxorubicin on multidrug resistant human ATP-binding cassette, sub-family B, member 1 (ABCB1) gene-transfected mouse T-lymphoma cell line, and human PC-3 and LNCaP prostate cancer cell lines in vitro. The steroidal interaction with P-glycopro tein (ABCB1) was investigated by molecular docking. Results: Both the activity of steroid derivatives on inhibition of the ABCB1 pump and their interaction with doxorubicin are dependent on the substituent groups of the investigated steroidal structures. Even though the investigated steroid derivatives were found to have limited antiproliferative effect on the three different cancer cell lines, in combination with doxorubicin, most of them acted as good potentiators. The binding energies from molecular docking ranged from -6.43 to -9.88 kcal/mol. The predicted inhibition constants ranged from 0.1 to 10.1 μM. A significant negative correlation was found between binding energy and fluorescence activity ratio (R=-0.5, p=0.015). Conclusion: The effective compounds can be candidates of model molecules for possible application in the treatment of multidrug resistant cancer in rational drug design.

Original languageEnglish
Pages (from-to)2105-2112
Number of pages8
JournalAnticancer research
Volume35
Issue number4
Publication statusPublished - Apr 1 2015

Keywords

  • ABCB1 transporter
  • Mouse T-lymphoma
  • Multidrug resistance
  • PC-3 prostate cancer cell line
  • Steroids

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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