Earticle

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 abilities to inhibit proliferation of MCF-7 and MDA-MB-231 human breast cancer cells were evaluated by measuring cell death via induction of apoptosis. The compound 1 exerted a higher anti-proliferative activity in the human breast cancer cells compared with compound 2. Compound 1 induced significant proliferative inhibition and apoptosis in a dosedependent manner in MCF-7 human cancer cells. Treatment with compound 1 induced the increase in caspase (-3 and -9) activities, DNA repair enzyme poly-(ADP-ribose) polymerase (PARP) cleavage, and pro-apoptotic gene and the decrease in anti-apoptotic gene. Besides, NF-κB family and -dependent activated genes were downregulated 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-κB or -dependent pathway. Although further studies are needed, the present results suggest that compound 1 has a promising potential as valuable chemopreventive agents.

In present study, we isolated phloroglucinol derivative, 1-(3',5'-dihydroxyphenoxy)-7-(2'',4'',6-trihydroxyphenoxy)-2,4,9-trihydroxydibenzo-1,4-dioxin (1), from Ecklonia Cava and its potential inhibitory effect on adipocyte differentiation in 3T3-L1 cells. Lipid accumulation and expression of several genes associated with adipogenesis and lipolysis were examined at the end of differentiation period. Lipid accumulation was examined by measuring triglyceride contents and Oil-Red O staining. The expression levels of several genes and proteins were examined using reverse transcription-polymerase chain reaction (RT-PCR), real-time PCR and western blot analysis. Presence of compound 1 induced significant reduction of lipid accumulation and down-regulation of peroxisome proliferatoractivated receptor-g (PPARγ), sterol regulatory element-binding protein 1c (SREBP1c) and CCAAT/enhancer-binding proteins (C/EBPα) in a dose-dependent manner. Moreover, presence of compound 1 induced down-regulation of adipogenic target genes such as adipocyte fatty acid binding protein (aP2), fatty acid transport protein (FATP), fatty acid synthase (FAS), acyl-CoA synthetase 1 (ACS1), lipoprotein lipase (LPL) and leptin genes. According to the lipolytic response, compound 1 down-regulated perilipin and hormonesensitive lipase (HSL) and up-regulated tumor necrosis factor a (TNFa). Therefore, these results suggest that compound 1 might decrease lipid accumulation during adipocyte differentiation by modulation of adipogenesis and lipogenesis and compound 1 could be developed as a good functional agent to improve antiobesity.