Mode of action of 3-substituted propylamine cytotoxicity in culture cells

Cytotoxic effects on MDBK cells of various 3-substituted propylamines, including spermine and spermidine, were tested in culture in the presence of calf serum, and the possible mode of action was studied from the viewpoint of oxidative deamination leading to acrolein formation. The compounds were roughly classified in two groups with ic₅₀ values of 0.1 and 0.4mM under the conditions used. Phenyl derivatives of 3-substituted propylamines, 3-benzylaminopropylamine, and polyamines were included in the first group with ic₅₀ values of 0.1 mM, and acrolein was liberated from these compounds after incubation with bovine plasma amine oxidase. Alkyl derivatives of 3-substituted propylamines (with ic₅₀ values of 0.4mM), on the other hand, were unable to release acrolein after the oxidative deamination, which was further confirmed by a lack of liberation of acrolein from the authentic 3-butoxypropanal. These observations indicated that both the acrolein originating from the 3-substituted propanals, and the propanal as such, were possibly involved in manifestation of the cytotoxicity of the 3-substituted propylamines. Thus, spermine and spermidine may exert their cytotoxic effects on the cells in vitro by a combination of two mechanisms involving acrolein and oxidized polyamines.