Heart failure drug proscillaridin A targets MYC overexpressing leukemia through global loss of lysine acetylation.

ABSTRACT:

Background

Cardiac glycosides are approved for the treatment of heart failure as Na⁺/K⁺ pump inhibitors. Their repurposing in oncology is currently investigated in preclinical and clinical studies. However, the identification of a specific cancer type defined by a molecular signature to design targeted clinical trials with cardiac glycosides remains to be characterized. Here, we demonstrate that cardiac glycoside proscillaridin A specifically targets MYC overexpressing leukemia cells and leukemia stem cells by causing MYC degradation, epigenetic reprogramming and leukemia differentiation through loss of lysine acetylation.

Methods

Proscillaridin A anticancer activity was investigated against a panel of human leukemia and solid tumor cell lines with diff

SUBMITTER: Da Costa EM 

PROVIDER: S-EPMC6563382 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature