Induction of apoptosis by phloroglucinol derivative from Ecklonia Cava in MCF-7 human breast cancer cells

Phloroglucinol derivatives, dioxinodehydroeckol (1) and 1-(3',5'-dihydroxyphenoxy)-7-(2 '',4 '',6-trihydroxyphenoxy)-2,4,9-trihydroxydibenzo-1,4-dioxin (2), were isolated from Ecklonia Cava. Their ability to inhibit the proliferation of human breast cancer cells were evaluated by measuring cell death via induction of apoptosis. Compound 1 exerted a higher anti-proliferative activity in human breast cancer cells compared with compound 2. Furthermore, compound 1 induced a significant proliferative inhibition and apoptosis in a dose-dependent manner on MCF-7 human cancer cells. Treatment with compound 1 also induced the increase in caspase(-3 and -9) activity, DNA repair enzyme poly-(ADP-ribose) polymerase(PARP) cleavage, and pro-apoptotic gene and the decrease in anti-apoptotic gene. In addition, NF-kappa B family and -dependent activated genes were down-regulated by compound 1. These results indicated that the potential inhibitory effect of compound 1 against growth of MCF-7 human breast cancer cells might be associated with induction of apoptosis through NF-kappa B family and NF-kappa B dependent pathway. The present results suggest that compound 1 has a promising potential to be used as a valuable chemopreventive agent. (C) 2009 Elsevier Ltd. All rights reserved.