Iron Promotes Cardiac Doxorubicin Retention and Toxicity Through Downregulation of the Mitochondrial Exporter ABCB8.

ABSTRACT: In several cancers, the efflux and resistance against doxorubicin (DOX), an effective anticancer drug, are associated with cellular iron deficiency and overexpression of the mitochondrial exporter ABCB8. Conversely, decreased ABCB8 expression and disrupted iron homeostasis in the heart have been implicated in DOX-associated cardiotoxicity. While studies have demonstrated that altered iron status can modulate the susceptibility to DOX cardiotoxicity, the exact molecular mechanisms have not been clearly understood. Here, we hypothesized that iron stores influence cardiac ABCB8 expression and consequently cardiac retention and toxicity of DOX. First, we found that ABCB8 deficiency in cardiomyocytes decreased DOX efflux, increased DOX-induced toxicity, and decreased cell viability. Conversely,

SUBMITTER: Menon AV 

PROVIDER: S-EPMC8963208 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature