Engineering Amyloid Aggregation as a New Way to Eliminate Cancer Stem Cells by the Disruption of Iron Homeostasis.

Cancer stem cells (CSCs) play crucial roles in tumor initiation. Amyloid β (Aβ), which is associated with Alzheimer's disease (AD), has been identified to induce cytotoxicity in tumor cells besides brain cells. Herein, we find that oligomeric Aβ1-42 and Aβ1-40 (OAβ1-42 and OAβ1-40) can repress the viability of breast CSCs. Intriguingly, OAβ1-42 and OAβ1-40 preferentially induce the growth arrest of breast CSCs by contrast with the bulk cancer cells. Further studies indicate that OAβ1-42 and OAβ1-40 disturb iron homeostasis, which results in iron accumulation in lysosomes. The iron in lysosomes then induces ROS production by Fenton reaction, leading to breast CSC death. In vivo experiments show that the tumorigenesis of breast CSCs pretreated with OAβ1-42 is inhibited. These results reveal that OAβ1-42 and OAβ1-40 are multifaceted players with the ability to eliminate CSCs. Our work may provide a new clue to better understand the biological functions of amyloid oligomers.