Induction of apoptosis by 5,7-dihydroxy-8-nitrochrysin in breast cancer cells: the role of reactive oxygen species and Akt.

5,7-dihydroxy-8-nitrochrysin (NOC), a novel synthetic chrysin analogue, induces apoptosis in human cancer cells. We previously demonstrated that NOC possesses stronger cytotoxicity towards human colon carcinoma and human gastric carcinoma cells than chrysin. Herein, we demonstrate the mechanism by which NOC preferentially suppresses the viability of the MDA-MB-453 human breast cancer cell line (ER negative, Her2 overexpressing) and moderately suppresses the viability of the MCF-7 cell line (ER positive, Her2 low), but has little effect on the immortalized non-cancerous HBL-100 breast cell line (ER positive, Her2 low). Moreover, the results of our studies, for the first time, provide mechanistic evidence that NOC induces apoptosis by the generation of reactive oxygen species and Akt dephosphorylation. Our findings highlight a new mechanism responsible for NOC-induced apoptosis, and raise the possibility that NOC might be promising as a candidate for human breast cancer therapy.