Kusumoto iK., Kageyama K., Matsuda T., Tomura T.T., Munakata H., Tanaka H., Yazama F., Miwabr N.

Aim: To evaluate promotive effect of hyperthermia on the carcinostatic activity of synthesized omega-hydroxy fatty acids (wHFAs) and their ethylesters agaist Ehrlich ascites tumor (EAT) cells. Methods: EAT cells were cultured with either wHFAs or their ethylester derivatives in a water bath at either 37 °C or 42 °C for 30 min, followed by incubation in a CO2 incubator for 20 or 72 h. Mitochondrial 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 (wH16:0) was the most carcinostatic (at 37 °C – viability level: 60.0%; at 42 °C – 49.6% (WST-1)) among saturated and unsaturated wHFAs with 12, 15 or 16 carbon atoms, when administrated to EAT cells at 100 µM for 20 h. Carcinostatic activity was markedly enhanced by ethyl-esterization of saturated fatty acids, such as wH16:0 (at 37 °C – 42.3%; at 42 °C – 11.2% , ibid) and wH15:0 (at 37 °C – 74.6%; at 42 °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 (wH16:0 ethylesther: 1.3%; wH15:0 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 wH16:0 ethylester-exposed EAT cells underwent extensive injury, such as deformation of cell structure or disappearance of microvilli. Conclusions: wH16:0 ethylester possesses high carcinostatic activity in vitro in combination with hyperthermia and may be utilized as potent anticancer therapeutic agent.

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