title: Significant activity of ecdysteroids on the resistance to doxorubicin in mammalian cancer cells expressing the human ABCB1 transporter.
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.
authors.affiliation: Institute of Pharmacognosy, Faculty of Pharmacy, University of Szeged, Eötvös u. 6, 6720 Szeged, Hungary.
authors.forename: Ana
authors.initials: A
authors.lastname: Martins
authors.forename: Noémi
authors.initials: N
authors.lastname: Tóth
authors.forename: Attila
authors.initials: A
authors.lastname: Ványolós
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Béni
authors.forename: István
authors.initials: I
authors.lastname: Zupkó
authors.forename: József
authors.initials: J
authors.lastname: Molnár
authors.forename: Mária
authors.initials: M
authors.lastname: Báthori
authors.forename: Attila
authors.initials: A
authors.lastname: Hunyadi
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology*; D004336:Drug Antagonism; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D026461:Ecdysteroids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D013329:Structure-Activity Relationship
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D026461:Ecdysteroids; D004317:Doxorubicin