Potent Anticancer Efficacy of First-In-Class Cu and Au Metaled Phosphorus Dendrons with Distinct Cell Death Pathways.

First-in-class Cu and Au metaled phosphorus dendrons were synthesized and showed significant antiproliferative activity against several aggressive breast cancer cell lines. The data suggest that the cytotoxicity increases with reducing length of the alkyl chains, whereas the replacement of Cu with Au considerably increases the antiproliferative activity of metaled phosphorus dendrons. Very interestingly, we found that the cell death pathway is related to the nature of the metal complexed by the plain dendrons. Cu metaled dendrons showed a potent caspase-independent cell death pathway, whereas Au metaled dendrons displayed a caspase-dependent apoptotic pathway. The complexation of plain dendrons with Au increased the cellular lethality versus dendrons with Cu and promoted the translocation of Bax into the mitochondria and the release of Cytochrome C (Cyto C).