Significant activity of ecdysteroids on the resistance to doxorubicin in mammalian cancer cells expressing the human ABCB1 transporter

Ana Martins, Noémi Tóth, Attila Ványolós, Zoltán Béni, István Zupkó, József Molnár, Mária Báthori, Attila Hunyadi

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Multidrug resistance (MDR) is a major cause of failure of cancer chemotherapy. Fifty-eight ecdysteroids, herbal analogues of the insect molting hormone and their semisynthetic derivatives, were tested for their activity against L5178 mouse T-cell lymphoma cells (non-MDR) and their subcell line transfected with pHa MDR1/A retrovirus overexpressing the human ABCB1 efflux pump (MDR cell line). The compounds showed very low antiproliferative activities but modulated the efflux of rhodamine 123 mediated by the ABCB1 transporter. Roughly depending on the polarity, mild to strong synergism or antagonism was observed by combining ecdysteroids with doxorubicin, and specific structure-activity relationships were also found. Our results show the effect of ecdysteroids on MDR cancer cells for the first time. Less polar derivatives may serve as valuable leads toward a potent and safe resistance modulator. Biological significance of the resistance-increasing activity of the most abundant phytoecdysteroids including 20-hydroxyecdysone is yet to be clarified.

Original languageEnglish
Pages (from-to)5034-5043
Number of pages10
JournalJournal of Medicinal Chemistry
Volume55
Issue number11
DOIs
Publication statusPublished - Jun 14 2012

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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