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

Abstract

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. <i>In vivo</i> 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.