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-kappaB 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-kappaB family and NF-kappaB dependent pathway. The present results suggest that compound 1 has a promising potential to be used as a valuable chemopreventive agent.
Kong
Chang-Suk
CS
Marine Bioprocess Research Center, Pukyong National University, Busan 608-737, Republic of Korea.
Kim
Jung-Ae
JA
Yoon
Na-Young
NY
Kim
Se-Kwon
SK
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004396:Coloring Agents; D004249:DNA Damage; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D019254:Genes, bcl-2 / Q000187:drug effects / Q000235:genetics; D016158:Genes, p53 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D016328:NF-kappa B / Q000235:genetics; D000459:Phaeophyceae / Q000737:chemistry*; D010696:Phloroglucinol / Q000302:isolation & purification / Q000633:toxicity*; D018515:Plant Leaves / Q000378:metabolism; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D013778:Tetrazolium Salts; D013844:Thiazoles
D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D004396:Coloring Agents; D016328:NF-kappa B; D012334:RNA, Neoplasm; D013778:Tetrazolium Salts; D013844:Thiazoles; D010696:Phloroglucinol; D020169:Caspases; C022616:thiazolyl blue