Effects of ethyl-esterization, chain-lengths, unsaturation degrees, and hyperthermia on carcinostatic effect of omega-hydroxylated fatty acids.
OBJECTIVE
To evaluate promotive effect of hyperthermia on the carcinostatic activity of synthesized omega-hydroxy fatty acids (omega HFAs) and their ethylesters agaist Ehrlich ascites tumor (EAT) cells.


METHODS
EAT cells were cultured with either omegaHFAs or their ethylester derivatives in a water bath at either 37 degrees C or 42 degrees C for 30 min, followed by incubation in a CO2 incubator for 20 or 72 h. Mitochond-rial dehydrogenase-based WST-1 assay and trypan blue dye exclusion assay were then conducted after incubation. Morphological changes were observed by scanning electron microscopy (SEM).


RESULTS
Omega-HFA having a saturated 16-carbon straight-chain (omega H16:0) was the most carcinostatic (at 37 degrees C - viability level: 60.0%; at 42 degrees C - 49.6% (WST-1)) among saturated and unsaturated omegaHFAs with 12, 15 or 16 carbon atoms, when administrated to EAT cells at 100 microM for 20 h. Carcinostatic activity was markedly enhanced by ethyl-esterization of saturated fatty acids, such as omegaH16:0 (at 37 degrees C - 42.3%; at 42 degrees C - 11.2%, ibid) and omegaH15:0 (at 37 degrees C - 74.6%; at 42 degrees C - 25.3%, ibid), and their unsaturated counterparts were extremely effective only in combination with hyperthermia. Prolongation of the incubation period to 72 h at the same concentration increased appreciably their carcinostatic effect (omega H16:0 ethylesther: 1.3%; omegaH15:0 ethylesther: 8.0%). These values were also supported by dye exclusion assay. The carcinostatic activity enhanced more markedly by hyperthermia (1.2%; 2.1%, ibid). SEM shows that omegaH16:0 ethylester-exposed EAT cells underwent extensive injury, such as deformation of cell structure or disappearance of microvilli.


CONCLUSIONS
omega H16:0 ethylester possesses high carcinostatic activity in vitro in combination with hyperthermia and may be utilized as potent anticancer therapeutic agent.
Kusumoto
K
K
International Buddhist University, 3-2-1 Gakuenmae Habikino, Osaka 583-8501, Japan. kuskus@shitennoji.ac.jp
Kageyama
K
K
Matsuda
T
T
Tomura
T T
TT
Munakata
H
H
Tanaka
H
H
Yazama
F
F
Miwa
N
N
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000378:metabolism / Q000648:ultrastructure; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D004951:Esterification; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use*; D005260:Female; D006358:Hot Temperature; D051379:Mice; D008813:Mice, Inbred ICR; D008871:Microvilli / Q000187:drug effects / Q000648:ultrastructure; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000378:metabolism
D000970:Antineoplastic Agents; D005227:Fatty Acids