The physiological role of biogenic amines redox reactions in mitochondria. New perspectives in cancer therapy |
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Authors: | E Agostinelli G Tempera A Molinari M Salvi V Battaglia A Toninello G Arancia |
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Institution: | (1) Department of Biochemical Sciences “A. Rossi Fanelli”, Institute of Molecular Biology and Pathology, University of Rome “La Sapienza” and CNR, Rome, Italy;(2) Department of Technology and Health, Istituto Superiore di Sanità, Rome, Italy;(3) Department of Biological Chemistry, University of Padua, Institute of Neurosciences of the C.N.R., Padua, Italy |
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Abstract: | Summary. In tumours, polyamines and amine oxidases increase as compared to normal tissues. Cytotoxicity induced by bovine serum amine
oxidase (BSAO) and spermine is attributed to H2O2 and aldehydes produced by the reaction. Increasing the incubation temperature from 37 to 42 °C enhances cytotoxicity in cells
exposed to spermine metabolites. The combination BSAO/spermine prevents tumour growth, particularly well if the enzyme has
been conjugated with a biocompatible hydrogel polymer. Since the tumour cells release endogenous substrates of BSAO, the administration
of spermine is not required. Combination with hyperthermia improves the cytocidal effect of polyamines oxidation products.
Our findings show that multidrug resistant (MDR) cells are more sensitive to spermine metabolites than their wild-type counterparts,
due to an increased mitochondrial activity which induces the generation of intracellular ROS prior to the onset of mitochondrial
permeability transition (MPT). It makes this new approach attractive, since the development of MDR is one of the major problems
of conventional cancer therapy. |
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Keywords: | : Polyamines – Amine oxidase – Reactive oxygen species – Multidrug resistance – Mitochondria – Cancer |
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