Cytolytic mechanism of attenuated preparation (OK-432) of Streptococcus haemolyticus against ascites hepatoma, AH 130 and AH 41 C cells.

Abstract

In order to gain insight into the mechanisms by which OK-432 (a lyophilized preparation of an attenuated strain of Streptococcus haemolyticus) treatment lyzed tumor cells, the in vivo effect of the agent on some enzymes, cellular components and surface properties of ascites hepatoma, AH 130 and AH 41 C cells, was studied in comparison with the effect of 5-fluorouracil (5FU) and cyclophosphamide (CP) on these parameters. Administration of OK-432 (0.5 mg/rat/day) to AH 130 cell-bearing rats for 4 days was found to enhance leakage of intracellular potassium and calcium, cause a decrease in hexokinase activity, cause a decrease in saturated fatty acids but a significant increase in cholesterol, unsaturated fatty acids of total phospholipids and 2, 4, 6-trinitrobenzenesulfonate binding to phosphatidylethanolamine as compared with the control cells. OK-432 administered for 2 days to AH 41 C cell-bearing rats also enhanced the leakage of the intracellular cations and the proportion of arachidonic acid in total phospholipids. On the other hand, significant alterations of these parameters in the cells were not demonstrated by 5FU and CP treatments. OK-432 treatment is considered to have an important influence on the lipid metabolism of the cells resulting in an increase in membrane fluidity which is related to leakage of essential components and hexokinase, consequently the leakage appears to inhibit the cell growth.