Coenzyme Q0 induces apoptosis and modulates the cell cycle in estrogen receptor negative breast cancer cells

We postulated that methoxy-substituted cyclic compounds could inhibit estrogen receptor (ER) negative breast cancer growth in vitro. Therefore, this study assessed the cytotoxic potential of various methoxy-substituted cyclic compounds [7,8-dimethoxyflavone, 4-methoxyphenylacetic acid, 2-methoxyphenylacetic acid, 4-methoxybenzophenone, 5-methoxy-1-indanone, and coenzyme Q₀ (CoQ₀)] toward ER-negative human breast cancer cells (MDA-MB-231 and SKBr3). Cytotoxicity was assessed using the sulforhodamine B assay. CoQ₀ demonstrated the strongest cytotoxicity toward MDA-MB-231 and SKBr3 cells with IC₅₀ values of 1.7 μmol/l and 3.1 μmol/l, respectively, whereas the other compounds were either much less potent or completely lacked cytotoxicity toward both breast cancer cell lines. Therefore, only CoQ₀ was examined for its ability to modulate cell cycle progression and induce apoptosis. Cell cycle experiments, using propidium iodide staining and flow cytometry, demonstrated that CoQ₀ at 7.5 μmol/l increased the proportion of MDA-MB-231 cells in G₁/G₀-phase by 16.6±0.6% of control (P<0.05), and increased in the proportion of S-phase SKBr3 cells by 37.8±5.8% over control (P<0.05). Induction of apoptosis was determined using propidium iodide/Annexin-V-FLUOS staining followed by flow cytometry. The results demonstrated that treatment with CoQ₀ (7.5 μmol/l) increased the proportion of apoptotic MDA-MB-231 and SKBr3 cells by 12-fold and 4-fold over control (P<0.05), respectively. Thus, CoQ₀ is a potent cytotoxic drug that induces apoptosis and modulates cell cycle progression in ER-negative breast cancer cells. Therefore, CoQ₀ is an appropriate candidate for further study and development as a potential drug for ER-negative breast cancer.