Simultaneous Targeting of NQO1 and SOD1 Eradicates Breast Cancer Stem Cells via Mitochondrial Futile Redox Cycling.

ABSTRACT: Triple-negative breast cancer (TNBC) contains the highest proportion of cancer stem-like cells (CSC), which display intrinsic resistance to currently available cancer therapies. This therapeutic resistance is partially mediated by an antioxidant defense coordinated by the transcription factor NRF2 and its downstream targets that include NAD(P)H quinone oxidoreductase 1 (NQO1). In this study, we identified the antioxidant enzymes NQO1 and superoxide dismutase 1 (SOD1) as therapeutic vulnerabilities of ALDH+ epithelial-like CSCs and CD24-/loCD44+/hi mesenchymal-like CSCs in TNBC. Effective targeting of these CSC states was achieved by using isobutyl-deoxynyboquinone (IB-DNQ), a potent and specific NQO1-bioactivatable futile redox cycling molecule, which generated large amounts of reactive ox

SUBMITTER: Luo M 

PROVIDER: S-EPMC11647209 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature