Discovery of a selective TRF2 inhibitor FKB04 induced telomere shortening and senescence in liver cancer cells.

ABSTRACT: Telomere repeat binding factor 2 (TRF2), a critical element of the shelterin complex, plays a vital role in the maintenance of genome integrity. TRF2 overexpression is found in a wide range of malignant cancers, whereas its down-regulation could cause cell death. Despite its potential role, the selectively small-molecule inhibitors of TRF2 and its therapeutic effects on liver cancer remain largely unknown. Our clinical data combined with bioinformatic analysis demonstrated that TRF2 is overexpressed in liver cancer and that high expression is associated with poor prognosis. Flavokavain B derivative FKB04 potently inhibited TRF2 expression in liver cancer cells while having limited effects on the other five shelterin subunits. Moreover, FKB04 treatment induced telomere shortening and increa

SUBMITTER: Qiu YD 

PROVIDER: S-EPMC11130216 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature