{"database":"biostudies-other","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["2(1)"],"submitter":["Vine KL"],"journal":["Heliyon"],"pagination":["e00060"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4945850"],"abstract":["The search for novel anticancer therapeutics with the ability to overcome multi-drug resistance (MDR) mechanisms is of high priority. A class of molecules that show potential in overcoming MDR are the N-alkylated isatins. In particular 5,7-dibromo-N-alkylisatins are potent microtubule destabilizing agents that act to depolymerize microtubules, induce apoptosis and inhibit primary tumor growth in vivo. In this study we evaluated the ability of four dibrominated N-alkylisatin derivatives and the parent compound, 5,7-dibromoisatin, to circumvent MDR. All of the isatin-based compounds examined retained potency against the MDR cell lines; U937VbR and MES-SA/Dx5 and displayed bioequivalent dose-dependent cytotoxicity to that of the parental control cell lines. We show that one mechanism by which the isatin-based compounds overcome MDR is by circumventing P-glycoprotein (P-gp) mediated drug efflux. Thus, as the isatin-based compounds are not susceptible to extrusion from P-gp overexpressing tumor cells, they represent a promising alternative strategy as a stand-alone or combination therapy for treating MDR cancer."],"repository":["biostudies-other"],"pmcid":["PMC4945850"],"data_source":["Europe PMC"],"pubmed_authors":["Belfiore L","Wade S","Vine KL","Locke JM","Jones L","Ranson M","Minaei E"],"additional_accession":[]},"is_claimable":false,"name":"N-alkylated isatins evade P-gp mediated efflux and retain potency in MDR cancer cell lines.","description":"The search for novel anticancer therapeutics with the ability to overcome multi-drug resistance (MDR) mechanisms is of high priority. A class of molecules that show potential in overcoming MDR are the N-alkylated isatins. In particular 5,7-dibromo-N-alkylisatins are potent microtubule destabilizing agents that act to depolymerize microtubules, induce apoptosis and inhibit primary tumor growth in vivo. In this study we evaluated the ability of four dibrominated N-alkylisatin derivatives and the parent compound, 5,7-dibromoisatin, to circumvent MDR. All of the isatin-based compounds examined retained potency against the MDR cell lines; U937VbR and MES-SA/Dx5 and displayed bioequivalent dose-dependent cytotoxicity to that of the parental control cell lines. We show that one mechanism by which the isatin-based compounds overcome MDR is by circumventing P-glycoprotein (P-gp) mediated drug efflux. Thus, as the isatin-based compounds are not susceptible to extrusion from P-gp overexpressing tumor cells, they represent a promising alternative strategy as a stand-alone or combination therapy for treating MDR cancer.","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Jan","modification":"2019-03-27T02:18:25Z","creation":"2019-03-27T02:18:25Z"},"accession":"S-EPMC4945850","cross_references":{"pubmed":["27441242"],"doi":["10.1016/j.heliyon.2015.e00060 "]}}