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.