Heat enhancement of cytotoxicity induced by oxidation products of spermine in chinese hamster ovary cells

Abstract

This study investigates the potential of using polyamines as thermosensitizers, in the presence of bovine serum amine oxidase (BSAO), as a new anticancer strategy. The effect of hyperthermia on cytotoxicity of spermine oxidized by purified bovine serum amine oxidase was investigated in Chinese hamster ovary cells. Several different spermine concentrations were employed in the presence of BSAO at 37° and 42°. Cytotoxicity was considerably enhanced at 42°. Heat also increased the individual cytotoxicity of both exogenous H 2O 2 and the exogenous aldehyde acrolein. Thus, both of these species could contribute to the thermal enhancement of cytotoxicity caused by BSAO and spermine. The effect of temperature was especially marked in the presence of exogenous catalase. This cytotoxicity cannot be accounted for by H 2O 2 and was attributed to aldehyde(s). The involvement of aldehyde(s) in cytotoxicity at 42° was also confirmed by the complete inhibition of cytotoxicity with both exogenous aldehyde dehydrogenase and exogenous catalase. A particularly interesting finding, in the presence of exogenous catalase, was that conditions of BSAO and spermine (⩽50 μM) which were non-toxic at 37° became cytotoxic at 42°. This suggests that spermine-derived aldehyde(s), that were non-toxic at 37°, contributed to cytotoxicity at 42° and resemble thermosensitizers. The thermosensitizing activity of aldehyde(s) produced in the BSAO-catalysed oxidation of spermine has potential value for improving the therapeutic effects of hyperthermia and could be considered for future application in cancer therapy. Polyamines are present at elevated levels in tumour cells and have been considered as heat sensitizers. By delivering BSAO into tumour cells, toxic oxidation products of polyamines could be produced in situ for selective killing of tumour cells.