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

Autor: G. Tempera, Maurizio Bifulco, Michele Caraglia, Gaia Giuberti, Alberto Abbruzzese, Enzo Agostinelli, Silvia Zappavigna, Angela Lombardi, Monica Marra, Giovanni Vitale
Přispěvatelé: Marra, M., Lombardi, A., Agostinelli, E., Giuberti, G., Zappavigna, S., Tempera, G., Vitale, G., Bifulco, M., ABBRUZZESE SACCARDI, A., Caraglia, Michele, Marra, M, Lombardi, A, Agostinelli, E, Giuberti, G, Zappavigna, S, Tempera, G, Vitale, G, Abbruzzese, A, Caraglia, M
Jazyk: angličtina
Rok vydání: 2008
Předmět:
Polyamine
IFNalpha
Apoptosis
Docetaxel
medicine.disease_cause
Settore MED/13 - Endocrinologia
Antineoplastic Combined Chemotherapy Protocols
Tumor Cells
Cultured
Polyamines
Caspase 3
Drug Synergism
Flow Cytometry
Recombinant Proteins
Oncogene Protein v-akt
Biochemistry
Taxoids
Amine Oxidase (Copper-Containing)
Oxidation-Reduction
Intracellular
Signal Transduction
p38 mitogen-activated protein kinases
Blotting
Western
Alpha interferon
Antineoplastic Agents
Biology
Interferon alpha-2
Nitric Oxide
medicine
Animals
Humans
Molecular Biology
Cell Proliferation
Cell growth
Superoxide Dismutase
fungi
Bovine serum amine oxidase
Interferon-alpha
Cell Biology
Enzyme Activation
Oxidative stress
Cancer cell
Cancer research
ras Proteins
Oxidative stre
Cattle
Spermine
Lipid Peroxidation
Reactive Oxygen Species
IFNα
Popis: 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 O 2− , 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.
Databáze: OpenAIRE
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