MDL 72527 and spermine oxidation products induce a lysosomotropic effect and mitochondrial alterations in tumour cells.

E Agostinelli, G Tempera, L Dalla Vedova, M Condello, G Arancia

Index: Biochem. Soc. Trans. 35(Pt 2) , 343-8, (2007)

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Abstract

Cytotoxic products of polyamines generated in situ by an enzyme-catalysed reaction may be useful as a new avenue in combating cancer. This study demonstrated that MDR (multidrug-resistant) cancer cells (colon adenocarcinoma and melanoma) are significantly more sensitive than the corresponding WT (wild-type) ones to H(2)O(2) and aldehydes, the products of BSAO (bovine serum amine oxidase)-catalysed oxidation of spermine. Moreover, cytotoxicity was considerably greater when the treatment was carried out at 42 degrees C than at 37 degrees C. TEM (transmission electron microscopy) observations showed major ultrastructural alterations of the mitochondria. These were more pronounced in MDR than in WT cells. After treatment with BSAO/spermine, a higher mitochondrial membrane depolarization and an increased mitochondrial activity in drug-resistant cells were observed.