Ecdysteroid Derivatives that Reverse P-Glycoprotein-Mediated Drug Resistance
Roberta Bortolozzi, Andrea Luraghi, Elena Mattiuzzo, Alessandro Sacchetti, Alessandra Silvani, Giampietro Viola
Abstract
reduced the side population representing cancer stem cells, which are characterized by a high expression of ABC drug transporters. Further, in DAOY cells, the same two compounds synergized with cisplatin and vincristine, two drugs used commonly in the therapy of medulloblastoma. Molecular docking studies on the homology-modeled structure of the human P-glycoprotein provided a rationale for the biological results, validating the binding mode within the receptor site, in accordance with lipophilicity data and observed structure-activity relationship information. Altogether, the present results endorse these derivatives as promising P-gp inhibitors, and they may serve as candidates to reverse drug resistance in cancer cells.