Haemolytic activity, cytotoxicity and membrane cell permeabilization of semi-synthetic and natural lupane- and oleanane-type saponins.
The haemolysis of red blood cells inducing toxicity in most animals including humans is a major drawback for the clinical development of saponins as antitumour agents. In this study, the haemolytic and cytotoxic activities as well as the membrane cell permeabilization property of a library of 31 semi-synthetic and natural lupane- and oleanane-type saponins were evaluated and the structure-activity relationships were established. It was shown that lupane-type saponins do not exhibit any haemolytic activity and membrane cell permeabilization property at the maximum concentration tested (100 microM) independently of the nature of the sugar moieties. While oleanane-type saponins such as beta-hederin (25) and hederacolchiside A(1) (27) cause the death of cancer cell lines by permeabilizing the cellular membranes, lupane-type saponins seem to proceed via another mechanism, which could be related to the induction of apoptosis. Altogether, the results indicate that the cytotoxic lupane-type glycosides 10 and 22 bearing an alpha-l-rhamnopyranose moiety at the C-3 position represent promising antitumour agents for further studies on tumour-bearing mice since they are devoid of toxicity associated with the haemolysis of red blood cells.
Gauthier
Charles
C
Laboratoire LASEVE, Chaire de Recherche sur les Agents Anticancéreux d'Origine Naturelle, Université du Québec à Chicoutimi, Chicoutimi, Québec, Canada.
Legault
Jean
J
Girard-Lalancette
Karl
K
Mshvildadze
Vakhtang
V
Pichette
André
A
D000818:Animals; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000187:drug effects; D004912:Erythrocytes / Q000378:metabolism; D006461:Hemolysis; D006801:Humans; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D012503:Saponins / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D012756:Sheep; D014315:Triterpenes / Q000737:chemistry*; D053978:Pentacyclic Triterpenes
D009828:Oleanolic Acid; D012503:Saponins; D014315:Triterpenes; C413246:oleanane; C480546:lupane; D053978:Pentacyclic Triterpenes