Correlation of DNA synthesis-inhibiting activity and the extent of transmembrane permeation into tumor cells by unsaturated or saturated fatty alcohols of graded chain-length upon hyperthermia

The carcinostatic activity has been studied for fatty acids of diverse spec ies but scarcely for fatty alcohols. Three unsaturated fatty alcohols at 35 -50 muM inhibited DNA synthesis and the proliferation of tumor cells by a c ombination with hyperthermia to greater extents in the order: oleyl (C18:1) -> linoleyl (C18:2)-> alpha -linolenyl (C18:3) alcohol, which is an order i nverse to that known for the corresponding fatty acids (4). In contrast, tw o saturated fatty alcohols, palmityl (C16:0)- and stearyl (C18:0) alcohols, did not inhibit at the same concentrations. At 100 muM, palmityl alcohol i nhibited, whereas stearyl alcohol did not. The effective fatty alcohols app reciably permeated the cells. The inhibition of the unsaturated fatty alcoh ols on DNA synthesis and proliferation was nearly proportional to the amoun t of their intercellular accumulation at 37 degreesC or 42 degreesC; the mo st inhibitory, oleyl alcohol, was the most membrane-permeable, whilst inver sely the least inhibitory, alpha -linolenyl alcohol, was the least permeabl e. A proportional correlation was not observed for saturated fatty alcohols ; palmityl alcohol underwent an approximate 2-fold more abundant accumulati on than other fatty alcohols, but was weakly inhibitory. Thus, oleyl alcoho l may exert an antitumor action via appropriately efficient transmembrane p ermeation and a combination with hyperthermia.