High anticancer activity and apoptosis- and autophagy-inducing properties of novel lanthanide(iii) complexes bearing 8-hydroxyquinoline-N-oxide and 1,10-phenanthroline

Abstract

In the quest for rare earth metal complexes with enhanced cancer chemotherapeutic properties, the discovery of seven lanthanide(III) complexes bearing 8-hydroxyquinoline-N-oxide (NQ) and 1,10-phenanthroline (phen) ligands, i.e., [Sm^III(NQ)(phen)(H₂O)Cl₂] (Ln1), [Eu^II(NQ)(phen)(H₂O)Cl₂] (Ln2), [Gd^III(NQ)(phen)(H₂O)Cl₂] (Ln3), [Dy^III(NQ)(phen)(H₂O)Cl₂] (Ln4), [Ho^III(NQ)(phen)(H₂O)Cl₂] (Ln5), [Er^III(NQ)(phen)(H₂O)Cl₂] (Ln6), and [Yb^III(NQ)(phen)(H₂O)Cl₂] (Ln7), as potential anticancer drugs is described. Complexes Ln1–Ln7 exhibit high antiproliferative activity against cisplatin-resistant A549/DDP cells (IC₅₀ = 0.025–0.097 μM) and low toxicity to normal HL-7702 cells. Moreover, complex Ln1, and to a lesser extent Ln7, can upregulate the expression of LC3 and Beclin1 and downregulate p62 to induce apoptosis in cisplatin-resistant A549/DDP cell lines, which is related to the cell autophagy-inducing properties of Ln1 and Ln7. Furthermore, in vivo assays suggest that Ln1 significantly inhibits A549/DDP xenograft tumor growth (56.5%). These results indicate that lanthanide(III) complex Ln1 is a promising candidate as an anticancer drug against cisplatin-resistant A549/DDP cells.