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 species but scarcely for fatty alcohols. Three unsaturated fatty alcohols at 35-50 microM inhibited DNA synthesis and the proliferation of tumor cells by a combination with hyperthermia to greater extents in the order: oleyl (C18:1)-> linoleyl (C18:2)-> alpha-linolenyl (C18:3) alcohol, which is an order inverse to that known for the corresponding fatty acids (4). In contrast, two saturated fatty alcohols, palmityl (C16:0)- and stearyl (C18:0) alcohols, did not inhibit at the same concentrations. At 100 microM, palmityl alcohol inhibited, whereas stearyl alcohol did not. The effective fatty alcohols appreciably permeated the cells. The inhibition of the unsaturated fatty alcohols on DNA synthesis and proliferation was nearly proportional to the amount of their intercellular accumulation at 37 degrees C or 42 degrees C; the most inhibitory, oleyl alcohol, was the most membrane-permeable, whilst inversely the least inhibitory, alpha-linolenyl alcohol, was the least permeable. A proportional correlation was not observed for saturated fatty alcohols; palmityl alcohol underwent an approximate 2-fold more abundant accumulation than other fatty alcohols, but was weakly inhibitory. Thus, oleyl alcohol may exert an antitumor action via appropriately efficient transmembrane permeation and a combination with hyperthermia.
Takada
Y
Y
Department of Radiology, Osaka City University Medical School, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
Kageyama
K
K
Yamada
R
R
Onoyama
Y
Y
Nakajima
T
T
Hosono
M
M
Miwa
N
N
D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division; D002463:Cell Membrane Permeability / Q000187:drug effects; D003470:Culture Media; D004261:DNA Replication / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000187:drug effects*; D005233:Fatty Alcohols / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006358:Hot Temperature; D051379:Mice; D008813:Mice, Inbred ICR; D014407:Tumor Cells, Cultured / Q000378:metabolism
D003470:Culture Media; D004273:DNA, Neoplasm; D005233:Fatty Alcohols