[Studies on the purification of water-soluble holothurian glycosides from Apostichopus japonicus and their tumor suppressing activity].
To obtain water-soluble holothurian glycosides with high tumor suppressing activities from Apostichopus japonicus, macroporous resin, silica gel and gel-filtration column chromatograghy were used to purify the water-soluble holothurian glycosides, and their tumor suppressing activity and inducing apoptosis of tumor cells were examined in this study. The 70% ethanol fraction of macroporous resin column, the pSC-2 and pSC-3 fractions from silica gel column showed very strong tumor suppressing activity towards HeLa cells, A-549 lung cancer cells, SGC-7901 stomach cancer cells and Bel-7402 liver cancer cells. SC-2 and SC-3 fraction purified from Sephadex LH-20 gel-filtration column chromatography, with a purity above 99.6%, all had the properties of triterpenoid glycosides. Purified SC-2 fraction had remarkable tumor suppressing activity on HeLa cells in a dose- and time-dependent manner, and had prominent tumor suppressing activity to mouse S180 solid tumors in a dose-dependent manner. Besides, the SC-2 fraction also had remarkable ability in elevating mouse thymus index and spleen index. The purified SC-2 fraction could induce apoptosis of HeLa cells in a dose-dependent manner, and DNA fragmentation of HeLa cells occurred after treated 12 h with 10 mg x L(-1) and 50 mg x L(-1) of SC-2 fractions. From the results, it can be concluded that the purified SC-2 fraction of water-soluble holothurian glycosides has extremely strong tumor suppressing activity, and the suppression is realized by inducing tumor cells to undergo apoptosis. This study lays solid foundation for development of highly effective new natural anticancer agents from sea cucumbers.
Fan
Ting-jun
TJ
Department of Marine Biology, College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China. tjfan@mail.ouc.edu.cn
Yuan
Wen-peng
WP
Cong
Ri-shan
RS
Yang
Xiu-xia
XX
Wang
Wei-wei
WW
Jing
Zhao
Z
D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006027:Glycosides / Q000302:isolation & purification / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D009368:Neoplasm Transplantation; D011897:Random Allocation; D012510:Sarcoma 180 / Q000473:pathology*; D047528:Stichopus / Q000737:chemistry*; D047368:Tumor Burden / Q000187:drug effects
D000970:Antineoplastic Agents; D006027:Glycosides