MDL 72527 and spermine oxidation products induce a lysosomotropic effect and mitochondrial alterations in tumour cells.
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.
Agostinelli
E
E
Department of Biochemical Sciences A Rossi Fanelli, University of Rome La Sapienza and CNR, Biology and Molecular Pathology Institutes, Piazzale Aldo Moro 5, 00185 Rome, Italy. enzo.agostinelli@uniroma1.it
Tempera
G
G
Dalla Vedova
L
L
Condello
M
M
Arancia
G
G
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D006801:Humans; D008247:Lysosomes / Q000187:drug effects / Q000502:physiology*; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D010084:Oxidation-Reduction; D011700:Putrescine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D013096:Spermine / Q000378:metabolism* / Q000494:pharmacology*; D014617:Vacuoles / Q000187:drug effects / Q000502:physiology
C044445:MDL 72527; D013096:Spermine; D011700:Putrescine