Antiinvasive activity of hexadecylphosphocholine in vitro.

The antiinvasive and related effects of hexadecylphosphocholine (HePC), a newly synthesized antitumor phospholipid, were studied on malignant murine MO4 cells in vitro and compared to the effects produced by racemic - 1 - 0 - octadecyl - 2 - 0 - methylglycero - 3 - phosphocholine (ET-18-OCH3), the prototype of ether lipids. The effects on cell survival produced by both drugs, determined through the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium-bromide test, was moderate at the antiinvasive concentration of 30 micrograms for HePC and 10 micrograms for ET-18-OCH3 per ml. Growth in suspension culture and directional migration from MO4 spheroids explanted on solid substrate was reduced in the presence of 30 micrograms HePC per ml. Invasion of MO4 cells into precultured heart fragments (PHF) was variably inhibited in the presence of 30 micrograms HePC per ml, while the antiinvasive effect on two epithelial lines was more complete. Invasion was also inhibited in PHF pretreated with 30 micrograms HePC and 10 micrograms ET-18-OCH3 per ml for 48 hours followed by confrontation with MO4 spheroids in drug-free medium. This inhibition of invasion was maintained when PHF was pretreated and kept in drug-free medium for 7 days before confrontation with MO4 spheroids. It was our impression that this phenomenon was more obvious with ET-18-OCH3 than with HePC. After pretreatment of PHF followed by 7-day incubation in drug free-medium, a larger shift towards higher molecular weight of the N-linked cell surface glycosylpeptides (N-GP) was observed with ET-18-OCH3 than with HePC. Removal of terminal sialic acid moieties abolished the shift in PHF pretreated with HePC or ET-18-OCH3 followed or not by further incubation in drug-free medium. The antiinvasive effect on the malignant epithelial cells was complete at 30 micrograms HePC per ml. Areas of differentiation in close contact with the PHF were obvious. We concluded that both ET-18-OCH3 and HePC had antiinvasive activity in vitro. For MO4 cells, this antiinvasive activity was less variable with ET-18-OCH3 than with HePC.