Cytotoxicity to tumors by alpha, beta-dihydric long-chain fatty alcohols isolated from esterolysates of uncytotoxic sheep cutaneous wax: the dependence on the molecular hydrophobicity balance of N- or iso-alkyl moiety bulkiness and two hydroxyl groups.
Wool fatty alcohols (WF-Alc; C10-C33), separated by esterolysis of wool grease secreted from sheep sebaceous gland, inhibited growth of mouse Ehrlich ascites carcinoma (EAC) cells in contrast to no inhibition by unesterolysed wool grease. WF-Alc was fractionated by molecular distillation and subsequent octadecylsilica (ODS) gel liquid chromatography, showing that most of the growth-inhibitory activity was found in the most hydrophilic fraction with the lowest boiling-point (MW 200-300; C12-C20), ODS-HPLC of the fraction showed that most of the activity resided in two homogeneous fractions identified by GC-MS and 13C-/1H-NMR as alpha, beta-dihydric saturated fatty alcohols such as 1,2-hexadecanediol (n-C16(OH)2) and 16-methyl-1,2-heptadecanediol (iso-C18(OH)2), respectively. EAC cells implanted into mice were inhibited markedly by n-C16(OH)2 possessing a cytolysing ability and slightly by iso-C18(OH)2, but hardly by other alkyl-alpha, beta-diols (C12-C24) contained in WF-Alc. Thus, the antitumor activity of WF-Alc was exhibited only after saponification of uncytotoxic wool grease, showing necessity of unesterified hydroxyl groups, and was dependent upon the molecular hydrophobicity balance attributed to both hydroxyl groups and n- or iso-alkyl moiety bulkiness specified out of diverse species of fatty alcohols contained in WF-Alc.
Miwa
N
N
Division of Cell Biochemistry, Hiroshima Prefectural University School of BioScience, Japan.
Nakamura
S
S
Nagao
N
N
Naruse
S
S
Sato
Y
Y
Kageyama
K
K
D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification* / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D004354:Drug Screening Assays, Antitumor; D005233:Fatty Alcohols / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D008401:Gas Chromatography-Mass Spectrometry; D008175:Lung Neoplasms / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008810:Mice, Inbred C57BL; D009447:Neuroblastoma / Q000188:drug therapy; D012756:Sheep; D012867:Skin / Q000378:metabolism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014885:Waxes / Q000737:chemistry*; D014935:Wool / Q000737:chemistry*
D000970:Antineoplastic Agents; D005233:Fatty Alcohols; D014885:Waxes