ANTINEOPLASTIC AGENTS .45. SEA-CUCUMBER CYTOTOXIC SAPONINS

Separation of the cytotoxic and antineoplastic constituents, guided by bioassay, led in each case to a complex of lanostane type saponins characteristic of sea cucumber Cuvierian organ toxins. The major cytotoxic component of each saponin mixture was isolated and designated stichostatin 1, thelenostatin 1 and actinostatin 1, respectively. A description of the isolation, purification and partial characterization of stichostatin 1 provided a summary of the techniques found most useful in this 1st detailed study of sea cucumber cytotoxic constituents. Antineoplastic effects were noted mouse P-388 and L-1210 leukemia cells and human 9KB oral carcinoma cells. A definitive structural elucidation of these 3 new cytotoxic saponins, combined with further cytotoxic and antineoplastic evaluations, will be undertaken. Presently available evidence indicates that such sea cucumber saponins have potentially useful and interesting biological properties. The inhibition of cell growth by the 3 tetracyclic triterpene saponins described in this report may be due to RNA and protein synthesis inhibition.