Cytotoxicity of docosahexaenoic acid and eicosapentaenoic acid in tumor cells and the dependence on binding to serum proteins and incorporation into intracellular lipids

Docosahexaenoic acid (DHA) inhibited the DNA synthesis in Ehrlich ascites t umor cells more markedly than eicosapentaenoic acid (EPA), which was more i nhibitory than oleic-, linoleic-, linolenic-, and arachidonic acids. Their activities augmented according to the increase of number of double bonds in the molecule. To correlate the cytotoxicity with lipid syntheses in the ce lls, distribution of EPA and DHA incorporated into cellular lipids was asse ssed. EPA was incorporated into triglycerides (TG) and DHA into phosphatidy lcholine (PC). These synthesis into TG and PC etc., which shattered from cy totoxicity, may be involved in tumor-cellular protecting actions against EP A or DHA. EPA and DKA involved in cytotoxicity exhibition are their free ac id forms. Thus, as an anticancer reaction, intracellular accumulation in th e free acid form of DHA was more marked than that of EPA.