Cell kill and cytostasis by ET-18-OCH3 and heat.

BACKGROUND

The ether lipid analogue 1-octadecyl-2-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3) is known to have plasma membrane interacting antitumor activity. However, the mechanism and the mode of action of its activity remain to be elucidated fully.

MATERIALS AND METHODS

In this study, the proportion of the inhibitory effects resulting either from direct cell kill or from cytostasis induced by (ET-18-OCH3) alone or in combination with heat in BG-1 human ovarian carcinoma cells was quantitated.

RESULTS

The magnitude of both cell kill and cytostasis in BG-1 cells was dependent on the concentration of ET-18-OCH3 and the duration of exposure. Cell kill induced by exposure to 2 or 8 microM ET-18-OCH3 for 1-14 days could be expressed as a simple exponential function of exposure dose (concentration x time). As assayed by colony formation, cell survival after continuous exposure to the drug was significantly reduced from that measured when the drug was removed and the cells were incubated for 14 days in drug-free medium.

CONCLUSIONS

We conclude that ET-18-OCH3 induces substantial cytostasis as well as cell kill in BG-1 cells and that this cytostasis is directly proportional to the amount of cell kill induced. These data are important in determining appropriate treatment regimens using ET-18-OCH3, either alone or in combination with other anticancer agents.