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 H2O2 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°C than at 37°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.
MDL 72527 and spermine oxidation products induce a lysosomotropic effect and mitochondrial alterations in tumour cells
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E. Agostinelli, G. Tempera, L. Dalla Vedova, M. Condello, G. Arancia; MDL 72527 and spermine oxidation products induce a lysosomotropic effect and mitochondrial alterations in tumour cells. Biochem Soc Trans 1 April 2007; 35 (2): 343–348. doi: https://doi.org/10.1042/BST0350343
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