RT Journal Article SR Electronic T1 Benzoxazole-based Zn(II) and Cu(II) Complexes Overcome Multidrug-resistance in Cancer JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 6181 OP 6187 DO 10.21873/anticanres.12971 VO 38 IS 11 A1 GABRIELLA SPENGLER A1 ANNAMÁRIA KINCSES A1 BÁLINT RÁCZ A1 BORISZ VARGA A1 GENKI WATANABE A1 RYOSUKE SAIJO A1 HIROSHI SEKIYA A1 EIJI TAMAI A1 JUN MAKI A1 JOSEPH MOLNÁR A1 MASAMI KAWASE YR 2018 UL http://ar.iiarjournals.org/content/38/11/6181.abstract AB Background/Aim: Multidrug resistance (MDR) represents a significant impediment to successful cancer treatment. In this study, novel metal [Zn(II), Cu(II), Mg(II), Ni(II), Pd(II), and Ag(I)] complexes of 2-trifluoroacetonylbenzoxazole previously synthesized and characterized by our group were tested for their MDR-reversing activity in comparison with the free ligands in L5178Y mouse T-lymphoma (MDR) cells transfected with human ATP-binding cassette sub-family B member 1 (ABCB1; P-glycoprotein) gene. Materials and Methods: Cytotoxic and antiproliferative effects of the complexes were assessed by the thiazolyl blue tetrazolium bromide (MTT) method. Modulation of ABCB1 activity was measured by rhodamine 123 accumulation assay using flow cytometry. The apoptosis-inducing activity of some complexes was also tested on the multidrug resistant L5178Y mouse T-lymphoma cells, using the annexin-V/propidium iodide assay. Results: When compared to the free ligand, a remarkable enhancement in MDR reversal and cytotoxic activity was found for the Zn(II) and Cu(II) complexes. The activity of the complexes proved to be up to 29- and 5-fold higher than that of the ligands and the ABCB1 inhibitor verapamil as positive control, respectively. The complexes possessed a remarkable potential to induce apoptosis of MDR cells. Conclusion: Our results suggest that the Zn(II) and Cu(II) complexes display significant MDR-reversing activity in a dose-dependent manner and possess strong cytotoxic activity and a remarkable potential to induce apoptosis in MDR L5178Y mouse T-lymphoma cells.