Systematic synthesis of low-molecular weight fucoidan derivatives and their effect on cancer cells.
Low-molecular weight type I and II fucoidan derivatives with different sulfation patterns were designed and systematically synthesized from the corresponding common key intermediate and their anti-proliferative activities and apoptosis-inducing activities against human breast cancer (MCF-7) and human cervical epithelioid carcinoma (HeLa) cells were evaluated. Our results demonstrated that one of the type II fucoidan derivatives, 9, effectively reduced the number of viable MCF-7 and HeLa cells in a dose-dependent manner without causing cytotoxicity toward normal WI-38 cells, and that the anti-proliferative activity of 9 was comparable to that of fucoidan 2 isolated from Fucus vesiculosus. Moreover, it was found that both 2 and 9 exhibited similar apoptosis-inducing activities through activation of caspase-8 and -9 on MCF-7 and HeLa cells, respectively.
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hoyoshi, Kohoku-ku, Yokohama 223-8522, Japan. dtak@applc.keio.ac.jp toshima@applc.keio.ac.jp.
Akihiro
A
Kasai
Shinsuke
S
Arafuka
Nozomi
N
Koshiba
Daisuke
D
Takahashi
Kazunobu
K
Toshima
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D008856:Microscopy, Fluorescence; D015394:Molecular Structure; D008970:Molecular Weight; D011134:Polysaccharides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000970:Antineoplastic Agents; D011134:Polysaccharides; C007789:fucoidan