Spermine metabolism and radiation-derived reactive oxygen species for future therapeutic implications in cancer: an additive or adaptive response.

Abstract

Destruction of cells by irradiation-induced radical formation is one of the most frequent interventions in cancer therapy. An alternative to irradiation-induced radical formation is in principle drug-induced formation of radicals, and the formation of toxic metabolites by enzyme catalyzed reactions. Thus, combination therapy targeting polyamine metabolism could represent a promising strategy to fight hyper-proliferative disease. The aim of this work is to discuss and evaluate whether the presence of a DNA damage provoked by enzymatic ROS overproduction may act as an additive or adaptive response upon radiation and combination of hyperthermia with lysosomotropic compounds may improve the cytocidal effect of polyamines oxidation metabolites. Low level of X-irradiations delivers challenging dose of damage and an additive or adaptive response with the chronic damage induced by spermine oxidase overexpression depending on the deficiency of the DNA repair mechanisms. Since reactive oxygen species lead to membrane destabilization and cell death, we discuss the effects of BSAO and spermine association in multidrug resistant cells that resulted more sensitive to spermine metabolites than their wild-type counterparts, due to an increased mitochondrial activity. Since mammal spermine oxidase is differentially activated in a tissue specific manner, and cancer cells can differ in term of DNA repair capability, it could be of interest to open a scientific debate to use combinatory treatments to alter spermine metabolism and deliver differential response.

• Authors: Roberto Amendola, Manuela Cervelli, Giampiero Tempera, Emiliano Fratini, Luigi Varesio, Paolo Mariottini, Enzo Agostinelli
• Journal: Amino acids (Amino Acids) Vol. 46 Issue 3 Pg. 487-98 (Mar 2014) ISSN: 1438-2199 [Electronic] Austria
• PMID: 23999645 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Reactive Oxygen Species
• Spermine

Topics

• Animals
• DNA Repair
• Humans
• Neoplasms (metabolism, pathology, therapy)
• Reactive Oxygen Species (metabolism)
• Spermine (metabolism)
• X-Rays