Anticancer drugs and hyperthermia enhance cytotoxicity induced by polyamine oxidation products: a new approach for anti-cancer intervention

correlation between regulation of cell proliferation and
polyamine metabolism is described. The latter can enter protein synthesis
through the modification of eukaryotic initiation factor 5A (eIF5A) and the
formation of the peculiar amino acid hypusine. Specific inhibitors of
hypusine formation induce apoptosis that can be potentiated by the combination
with cytokines such as interferona (IFNa) that itself decreases
hypusine synthesis. We have also demonstrated that the concomitant
treatment of cancer cells with IFNa and the protein synthesis inhibitor
fusion protein TGFa=Pseudomonas Aeruginosa toxin synergize in inducing
cancer cell growth inhibition. Another way used by polyamines to
induce apoptosis is the generation of intracellular oxidative stress through
the interaction with bovine serum amine oxidase (BSAO). This enzyme
used simultaneously to spermine induces apoptosis, necrosis, inhibition of
cell proliferation and inhibition of DNA and protein synthesis in several
cell types. The enzymatic oxidation products of polyamine, H2O2 and
aldehyde(s) cause these effects. We have recently found that the cytotoxicity
of anti-cancer agents, either etoposide or docetaxel, in cancer cells is
potentiated in the presence of BSAO=Spermine. In conclusion, polyamine
metabolites could be useful in the design of new therapeutic strategies.