Combined treatment with emodin and a telomerase inhibitor induces significant telomere damage/dysfunction and cell death.

ABSTRACT: G-quadruplex telomeric secondary structures represent natural replication fork barriers and must be resolved to permit efficient replication. Stabilization of telomeric G4 leads to telomere dysfunctions demonstrated by telomere shortening or damage, resulting in genome instability and apoptosis. Chemical compounds targeting G4 structures have been reported to induce telomere disturbance and tumor suppression. Here, virtual screening was performed in a natural compound library using PyRx to identify novel G4 ligands. Emodin was identified as one of the best candidates, showing a great G4-binding potential. Subsequently, we confirmed that emodin could stabilize G4 structures in vitro and trigger telomere dysfunctions including fragile telomeres, telomere loss, and telomeric DNA damage. Howev

SUBMITTER: Liu R 

PROVIDER: S-EPMC6624283 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature