Spermine Oxidation Products Induce Mitochondrial Alterations on Tumor Cells

Cytotoxic products of polyamines generated in situ by an enzyme-catalyzed reaction may be useful as a new avenue in combating cancer. This study demonstrates that multidrug resistant (MDR) cancer cells (colon adenocarcinoma and melanoma) are significantly more sensitive than the corresponding wild type (WT)ones to hydrogen peroxide and aldehydes, the products of bovine serum amine oxidase (BSAO)-catalyzed oxidation of spermine. Transmission electron microscopy (TEM) observations showed the 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. The results suggest that enzymatically formed cytotoxic agents activate stress signal transduction pathways, leading to apoptotic cell death, mainly in multidrug resistant cell lines.