Comparative anti-mitotic effects of lithium gamma-linolenate, gamma-linolenic acid and arachidonic acid, on transformed and embryonic cells.

The effects of gamma-linolenic acid (GLA), the lithium salt of gamma-linolenic acid (LiGLA) and arachidonic acid (AA) were compared at doses of 50 microg/ml for periods of 6 and 24 h on cell cycle progression and apoptosis induction in transformed and in normal cells. In WHCO3 (oesophageal cancer) cells and on primary embryonic equine lung cells, we found LiGLA to be the most effective in apoptosis induction. After 24 h, 94% of the WHCO3 cancer cells and 44% of the primary embryonic equine lung cells exposed to LiGLA were apoptotic. The WHCO3 cancer cells were also very susceptible to the apoptosis-inducing effects of AA (56%) and GLA (44%), whereas the embryonic equine lung cells were much less affected by these two fatty acids. After 6 h exposure to all three compounds, most of the cycling WHCO3 cancer cells were blocked in S-phase. After 24 h treatment, some of the S-phase cells exposed to AA and GLA were apparently able to move into the G2/M phase, the LiGLA exposed cells were mostly apoptotic and no cycling cells were present. The primary embryonic equine lung cells were fairly resistant to the cytotoxic effects of GLA and AA. From our studies we conclude that, although LiGLA was the most toxic to the cancer cells, it is apparently less selective, compared to AA and GLA, in the killing of cancer and normal cells. It would also appear that the lithium might have added to the cytotoxic effects of LiGLA. The mechanism needs to be clarified.