Cytotoxic Effects of 7-O-Butyl Naringenin on Human Breast Cancer MCF-7 Cells

The effect of 7-O-butyl naringenin (BN), a chemically synthesized derivative of naringenin, was tested on the proliferation of human breast cancer MCF-7 cells. BN inhibited the proliferation of MCF-7 cells in dose-dependent manner (IC∧50: 67.5±2.1 μM), resulting in an increase in the sub-G1 phase cell population. BN induced the generation of intracellular reactive oxygen species (ROS), which were reduced by pretreatment with N-acetylcysteine (NAC). BN also increased the phosphorylation of stress-activated protein kinase/c-Jun NH₄-terminal kinase 1/2 (SAPK/JNK1/2), c-Jun, and p38. However, the phosphorylation of extracellular-regulated kinase 1/2 (Erk1/2) was decreased in BN-treated cells. Pretreatment of cells with the specific inhibitors SP600125 and SB203580 diminished the BN-induced activation of SAPK/JNK1/2 and p38, respectively. These results indicate that the BN-induced cytotoxicity of MCF-7 cells is mediated by the generation of ROS as well as through the p38, SAPK/JNK1/2, and c-Jun activation signaling pathways. BN may therefore possess chemotherapeutic potential as an anti-proliferative agent.