A chalcone/quinolone hybrid drug (COQM) triggers oxidative stress, DNA damage, and apoptosis to induce selective antiproliferative effects in breast cancer cells

Abstract

COQM is a newly developed hybrid compound of chalcone and quinolone, both of which are known to have anticancer and anti-inflammatory abilities. However, the anticancer effect of COQM on breast cancer cells is not yet well understood, and its safety has not been fully investigated. In this study, we investigated the anticancer ability and mechanism of COQM against triple-negative breast cancer cells (TNBC; HCC1937) and non-TNBC cells (SKBR-3) compared with normal breast cells (H184B5F5/M10 (M10)). We found that COQM-treated breast cancer cells exhibited less proliferation, more subG1 accumulation and apoptosis (annexin V), and an increased activation of apoptotic signaling regulators, such as caspases 3, 8, and 9, compared with normal cells. These effects were attenuated by N-acetylcysteine (NAC) pretreatment, suggesting that these anti-breast cancer mechanisms are mediated by oxidative stress. COQM-induced oxidative stress responses were further confirmed by flow cytometry, which revealed a greater generation of reactive oxygen species and mitochondrial superoxide and lower mitochondrial membrane potential and glutathione, in breast cancer than normal cells, attenuated by NAC. Similarly, COQM exhibits greater oxidative stress-dependent DNA damages for γH2AX and 8-hydroxy-2-deoxyguanosine in breast cancer than normal cells, as confirmed via NAC. In brief, we found that COQM exerted anti-breast cancer effects and oxidative stress-mediated mechanisms, and caused minimal damage to normal cells.