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

Journal of Medicinal Chemistry
Ana MartinsAttila Hunyadi

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.

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Citations

Dec 18, 2013·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ana MartinsAttila Hunyadi
Nov 26, 2015·Magnetic Resonance in Chemistry : MRC·Tamás GátiGábor Tóth
Apr 1, 2014·Biotechnology Advances·Tsanko S GechevBernd Mueller-Roeber
Nov 5, 2016·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Judit MüllerGyörgy T Balogh
Jan 27, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Attila HunyadiGábor Tóth
Mar 24, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Godwin A DziwornuSuthananda N Sunassee
Oct 12, 2013·Magnetic Resonance in Chemistry : MRC·Attila BalázsGábor Tóth
Aug 14, 2020·Journal of Natural Products·Roberta BortolozziGiampietro Viola
Mar 12, 2021·The Journal of Nutritional Biochemistry·Zhihao QuAiling Liu
Aug 14, 2021·Acta Pharmaceutica Sinica. B·Niranjan DasAnupam Bishayee
May 26, 2018·ACS Medicinal Chemistry Letters·Gaia FumagalliDaniele Passarella
Sep 17, 2021·International Journal of Environmental Health Research·Homayoon Yazdanshenas, Majid Tafrihi

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