Selective elimination of quiescent cancer cells by dequalinium chloride via ROS-mediated ferroptosis.

Quiescent cancer cells (QCCs) drive tumor dormancy and recurrence through their resistance to conventional therapies. Furthermore, because QCCs rely on oxidative phosphorylation and maintain a fragile redox balance, we hypothesized that they harbor a targetable redox vulnerability. Here, we show that the mitochondria-targeted agent dequalinium chloride (DQ) selectively kills QCCs in hypoxia- and nutrient limitation-induced quiescent models, including H2228 cells, multicellular spheroids, and colorectal cancer organoids, while sparing proliferating cells and normal fibroblasts. DQ induces ROS accumulation beyond the survival threshold of QCCs, leading to lipid peroxidation and ferroptotic cell death, whereas proliferating cells undergo limited caspase-independent apoptosis. These findings highlight redox imbalance as an actionable vulnerability of QCCs and position DQ as a potential repurposed agent for eliminating QCCs.