Bovine serum amine oxidase and spm potentiate docetaxel and interferon-α effects in inducing apoptosis on human cancer cells through the generation of oxidative stress

It was previously demonstrated that bovine serum amine-oxidase (BSAO) and SPM (SPM) addition to cancer
cells induces cell growth inhibition and over-run the multi-drug resistance (MDR) phenotype through the
oxidative stress caused by polyamine metabolites. In this study, it is reported that BSAO/SPM enzymatic
system antagonizes the survival pathway induced by either docetaxel (DTX) or interferon alpha (IFNα) in
human epidermoid cancer KB cells. The combination of BSAO/SPM with either DTX or IFNα had a synergistic
effect on cell growth inhibition through apoptosis in both human epidermoid KB and breast cancer MCF-7
cell lines. The effects of the BSAO/SPM-DTX combination on apoptosis were caspase 3 and 9-dependent and
were paralleled by the enhancement of intracellular O2−, nitric oxide levels and of lipo-oxidation. The
scavenger moiety N-acetyl-cysteine antagonized the effects on apoptosis and cell growth inhibition induced
by the combination suggesting a role of the oxidative products of SPM. These effects occurred together with a
decrease of the physiological scavenger MnSOD and an increase of both p38 kinase activity and DNA damage.
The results suggest that DTX and IFNα could sensitize tumour cells to the oxidative stress and apoptosis
induced by BSAO/SPM through the induction of a survival ras-dependent pathway and the consequent
elevation of the intracellular polyamine pool. These data allow the design of new therapeutic strategy based
on the use of this combination in human neoplasms.