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In Silico Identification and In Vitro Evaluation of New ABCG2 Transporter Inhibitors as Potential Anticancer Agents.
Di Micco, Simone; Di Sarno, Veronica; Rossi, Martina; Vestuto, Vincenzo; Konno, Takumi; Novi, Sara; Tecce, Mario Felice; Napolitano, Valeria; Ciaglia, Tania; Vitale, Andrea; Gomez-Monterrey, Isabel Maria; Bifulco, Giuseppe; Bertamino, Alessia; Ostacolo, Carmine; Blasi, Paolo; Fasano, Alessio; Campiglia, Pietro; Musella, Simona.
Afiliación
  • Di Micco S; European Biomedical Research Institute of Salerno, Via S. De Renzi 50, 84125 Salerno, Italy.
  • Di Sarno V; Department of Pharmacy, University of Salerno, Via G. Paolo II, 84084 Fisciano, Italy.
  • Rossi M; Department of Pharmacy and Biotechnology, Via San Donato 19/2, 40127 Bologna, Italy.
  • Vestuto V; Center for Applied Biomedical Research (CRBA), University of Bologna, 40126 Bologna, Italy.
  • Konno T; Department of Pharmacy, University of Salerno, Via G. Paolo II, 84084 Fisciano, Italy.
  • Novi S; Department of Pediatrics, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Tecce MF; Department of Pediatrics, Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital for Children, Boston, MA 02114, USA.
  • Napolitano V; Department of Pharmacy, University of Salerno, Via G. Paolo II, 84084 Fisciano, Italy.
  • Ciaglia T; Department of Pharmacy, University of Salerno, Via G. Paolo II, 84084 Fisciano, Italy.
  • Vitale A; Department of Pharmacy, University of Salerno, Via G. Paolo II, 84084 Fisciano, Italy.
  • Gomez-Monterrey IM; Department of Pharmacy, University of Salerno, Via G. Paolo II, 84084 Fisciano, Italy.
  • Bifulco G; Pineta Grande Hospital, Via Domiziana, km 30/00, 81030 Castel Volturno, Italy.
  • Bertamino A; Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131 Napoli, Italy.
  • Ostacolo C; Department of Pharmacy, University of Salerno, Via G. Paolo II, 84084 Fisciano, Italy.
  • Blasi P; Department of Pharmacy, University of Salerno, Via G. Paolo II, 84084 Fisciano, Italy.
  • Fasano A; Department of Pharmacy, University of Salerno, Via G. Paolo II, 84084 Fisciano, Italy.
  • Campiglia P; Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131 Napoli, Italy.
  • Musella S; Department of Pharmacy and Biotechnology, Via San Donato 19/2, 40127 Bologna, Italy.
Int J Mol Sci ; 24(1)2022 Dec 31.
Article en En | MEDLINE | ID: mdl-36614168
Different molecular mechanisms contribute to the development of multidrug resistance in cancer, including increased drug efflux, enhanced cellular repair mechanisms and alterations of drug metabolism or drug targets. ABCG2 is a member of the ATP-binding cassette superfamily transporters that promotes drug efflux, inducing chemotherapeutic resistance in malignant cells. In this context, the development of selective ABCG2 inhibitors might be a suitable strategy to improve chemotherapy efficacy. Thus, through a multidisciplinary approach, we identified a new ABCG2 selective inhibitor (8), highlighting its ability to increase mitoxantrone cytotoxicity in both hepatocellular carcinoma (EC50from 8.67 ± 2.65 to 1.25 ± 0.80 µM) and transfected breast cancer cell lines (EC50from 9.92 ± 2.32 to 2.45 ± 1.40 µM). Moreover, mitoxantrone co-administration in both transfected and non-transfected HEK293 revealed that compound 8 notably lowered the mitoxantrone EC50, demonstrating its efficacy along with the importance of the ABCG2 extrusion pump overexpression in MDR reversion. These results were corroborated by evaluating the effect of inhibitor 8 on mitoxantrone cell uptake in multicellular tumor spheroids and via proteomic experiments.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 / Neoplasias / Antineoplásicos Tipo de estudio: Diagnostic_studies Límite: Humans Idioma: En Revista: Int J Mol Sci Año: 2022 Tipo del documento: Article País de afiliación: Italia

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 / Neoplasias / Antineoplásicos Tipo de estudio: Diagnostic_studies Límite: Humans Idioma: En Revista: Int J Mol Sci Año: 2022 Tipo del documento: Article País de afiliación: Italia