Potential interactions between metal-based phenanthroline drugs and the unfolded protein response endoplasmic reticulum stress pathway

Abstract The unfolded protein response has recently been implicated as a mechanism by which 1,10-phenanthroline-containing coordination compounds trigger cell death. We explored the interaction of two such compounds—one containing copper and one manganese—with endoplasmic reticulum (ER) stress. Pretreatment with anisomycin significantly enhanced cytotoxic activity both metal-based in A2780, but only copper-based compound A549 cells. effects pretreatment tunicamycin were dependent on nature metal center compounds. In A2780 cells, action was reduced at high concentration. contrast, cells efficacy manganese all tested concentrations. Intriguingly, some impact free 1,10-phenanthroline also observed These results are discussed context emerging evidence that ER plays role 1,10-phenanthroline-based