pulsatilla-saponin-d and Hemolysis

The strong hemolytic toxicity of pulsatilla saponin D (1, HD

Topics: A549 Cells; Animals; Antineoplastic Agents; Apoptosis; Cell Cycle Checkpoints; Cell Line, Tumor; Cytotoxins; Erythrocytes; G1 Phase; Hemolysis; Humans; KB Cells; Lung Neoplasms; MCF-7 Cells; Rabbits; Saponins; Structure-Activity Relationship

The strong haemolytic activity of Pulsatilla saponin A (PSA), D (PSD) hampered their clinical development of antitumor agents. In order to solve this problem, C-28 position modification derivatives of PSA/PSD were synthesized. The cytotoxicity and haemolytic activity of these compounds were evaluated. Structure-activity relationship and structure-toxicity relationship had been observed. The mice acute toxicity of compound 11 was reduced greatly than that of PSA. This study indicates that compound 11 may represent an interesting class of potent antitumor agents from triterpenoid saponins avoiding the haemolysis problem. The present study has important significance for the development of antitumor saponins.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Survival; Drug Screening Assays, Antitumor; Hemolysis; Humans; Mice; Saponins; Structure-Activity Relationship

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.

Topics: Animals; Cell Line, Tumor; Cell Membrane Permeability; Erythrocytes; Hemolysis; Humans; Oleanolic Acid; Saponins; Sheep; Triterpenes