Cytotoxic effects of daunomycin-fatty acid complexes on rat hepatoma cells.

The anthracycline antibiotic drug daunomycin has been coupled to fatty acids through formation of a peptide bond with the amino group of its lyxose residue. The arachidonic (C20:4) and docosahexaenoic (C22:6) acid derivatives showed potent in vitro and in vivo cytotoxic activity against rat hepatoma cells producing alpha-fetoprotein. With the exception of the acetate derivative, the complexes with saturated fatty acids showed no activity. The in vivo toxicity of the free daunomycin is markedly diminished when present in the form of these derivatives. The antitumor activities of the polyene fatty acid complexes appear to depend upon the high degree of affinity of alpha-fetoprotein for these acids. These results strongly suggest the use of daunomycin or other cytotoxic drug:polyene fatty acid complexes in the therapy of human tumors producing alpha-fetoprotein.