[Comparative study of cytotoxic and hemolytic effects of triterpenoids isolated from Ginseng and Sea cucumber].
Specific features of cytotoxic (against tumor cells), hemolytic, and liposomal (effect on permeability) activities of triterpenoids isolated from sea cucumbers and ginseng roots were studied. It was shown that oleanolic acid, protopanaxatriol, and protopanaxadiol at 5 to 20 micrograms/ml inhibited the growth of tumor cells, while at doses up to 100 micrograms/ml, they did not induce hemolysis or changes in liposome permeability. Monoglucosides of protopanaxadiol, Rh2, Rg3, and substance K exerted moderate cytotoxic and membrane activities. The membrane sensitivity to these glucosides was inversely proportional to the membrane content of cholesterol. The cytotoxicity of the protopanaxadiol-active glycosides increased with a decrease of pH of the medium. All studied glycosides did not affect the cell and model lipid membranes. The activity of the oleanolic acid glycoside, ginsenoside Z-R1, depended to a great extent on the pH of the medium. The decrease of pH from 7.4 to 5.6 increased the membranolytic activities by more than one order of magnitude. Glycosides from sea cucumbers, echinosides A and B, holothurins A and B, holotoxin A1, and cucumarioside G1, had very high cytotoxic and liposomal activities. Addition of cholesterol to cell membranes enhanced the cytotoxic effects of these glycosides. The ginsenosides with two carbohydrate moieties (bisdesmosides), as well as all the panaxatriol glycosides we studied did not exhibit cytotoxic activities against tumor cells or alter the permeability of model lipid and lipid-sterol membranes. The triterpenoids studied were classified into four categories in accordance with their membranotropic activities. A possible protective role of these glycosides in the organism-producent is discussed.
Popov
A M
AM
Pacific Institute of Bioorganic Chemistry, Far East Division of the Russian Academy of Sciences, Vladivostok, 690022 Russia. Popov@piboc.marine.ru
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008081:Liposomes; D005894:Panax / Q000737:chemistry*; D012616:Sea Cucumbers / Q000737:chemistry*; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D008081:Liposomes; D014315:Triterpenes