DHL-11, a novel prieurianin-type limonoid isolated from <i>Munronia henryi</i>, targeting IMPDH2 to inhibit triple-negative breast cancer.

ABSTRACT: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, characterized by the poorest prognosis, and poses a significant threat to women's health. In this study, we identified two novel prieurianin-type limonoids extracted from Munronia henryi, one of which, named DHL-11, exhibited antitumor activity against TNBC cells. DHL-11 suppressed cell proliferation and migration, induced G2/M cell cycle arrest and apoptosis, and effectively increased the accumulation of reactive oxygen species (ROS) and cellular DNA damage in TNBC cells. Mechanistically, we found that DHL-11 binds to the non-catalytic pocket of IMPDH2 and disrupts the interaction between IMPDH2 and FANCI, leading to the degradation of the IMPDH2 protein. The decrease of IMPDH2 protein reduced gua

SUBMITTER: Zhu Y 

PROVIDER: S-EPMC12827893 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature