Dieckol, isolated from Ecklonia stolonifera, induces apoptosis in human hepatocellular carcinoma Hep3B cells.
Phlorotannins have been reported to demonstrate several biological properties, including antioxidant activity, and activities useful in the treatment of diabetic complications and in chemoprevention of several vascular diseases. In this study, we focused on the apoptosis induced by dieckol, a marine algal phlorotannin isolated from Ecklonia stolonifera, on human hepatocellular carcinoma (HCC) Hep3B cells. Dieckol reduced the numbers of viable cells and increased the numbers of apoptotic cells in a dose-dependent manner. Immunoblotting analysis revealed that dieckol increased the expression levels of cleaved caspases-3, 7, 8, and 9, and cleaved poly(ADP-ribose) polymerase. Dieckol increased the permeability of mitochondrial membranes and the release of cytochrome c from mitochondria into the cytosol with apoptosis-inducing factor. In addition, dieckol induced increased expression of truncated Bid and Bim. The results indicate that dieckol induces apoptosis via the activation of both death receptor and mitochondrial-dependent pathways in HCC Hep3B cells.
Department of Microbiology, College of Natural Sciences, Pukyong National University, 45 Yongsoro, Namgu, Busan, 608-737, Korea.
Jin-Soo
JS
Yoon
Anandam
A
Kasin Yadunandam
Soon-Jin
SJ
Kim
Hee-Chul
HC
Woo
Hyeung-Rak
HR
Kim
Gun-Do
GD
Kim
D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D001572:Benzofurans / Q000302:isolation & purification / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D057809:HEK293 Cells; D006801:Humans; D008113:Liver Neoplasms; D008565:Membrane Proteins / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism; D010539:Permeability; D000459:Phaeophyceae / Q000737:chemistry*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D000072224:Bcl-2-Like Protein 11; D001572:Benzofurans; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; C503840:dieckol; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases