ENHANCEMENT OF CELL MEDIATED LYSIS OF TUMOUR CELLS BY CHELIDONIUM MAJUS L ALKALOIDS (UKRAIN)

A. LIEPINS

Memorial Univ., Fac. Med., St. John's, NF, Canada A1B 3V6

Alkaloids from Chelidonium majus L. conjugated to thiophosphoric acid yield non-toxic compound with a MW=1,470, named Ukrain (J. W. Nowicky, Laimgrubengasse 19/5, A-1060, Vienna, Austria). This compound has been reported to have therapeutic properties in a variety of cancer patients (Nowicky, J. W., IV Med. Cong. of Chemotherapy, Chemotherapia: Suppl No. 2, Vol 4, pp 1169-1171, 1985). Ukrain at 1.18 μM, was found to increase by 50 fold the cytolytic activity of spleen cells from C57BL/6 (H-2^b) mice alloimmunized (IP, for 18 days) with mastocytoma P815 (H-2^d) cells, (from 1.3 to 65.0% specific lysis, E/T=5:1, 3.5 hr/assays). The enhanced lytic activity was dose dependent and remained specific for the immunizing cells. The peritoneal exudate cells (PEC) lytic activity was increased from 7.0% to 25.0% specific lysis in the presence of 2.36 μM of Ukrain. The drug had no effect on the spontaneous ⁵¹Cr release of target cells within the concentration range used: 0.59 to 37.8 μM. Spleen cells from alloimmunized mice harvested after 14 days and cultured in vitro for 4 days in the presence or absence of 10 units/ml of rIL-2 were found to have a specific cytolytic activity of 25.0 and 16.3%, respectively. In the presence of 1.18 μM of Ukrain the cytolytic activity of both these effector cell populations was increased to 60.0%. In all assays the lytic activity remained specific for the immunizing tumour cells and the effects of Ukrain were dose dependent.