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Biophysical and biochemical characterization of a liposarcoma-derived recombinant MnSOD protein acting as an anticancer agent (Articolo in rivista)

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Biophysical and biochemical characterization of a liposarcoma-derived recombinant MnSOD protein acting as an anticancer agent (Articolo in rivista) (literal)

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Mancini A.; Borrelli A.; Schiattarella A.; Aloj L.; Aurilio M.; Morelli F.; Pica A.; Occhiello A.; Lorizio R.; Mancini R.; Sica A.; Mazzarella L.; Sica F.; Grieco P.; Novellino E.; Pagnozzi D.; Pucci P. and Rommelaere J. (2008)
Biophysical and biochemical characterization of a liposarcoma-derived recombinant MnSOD protein acting as an anticancer agent
in International journal of cancer (Print); Wiley-Liss, New York (Stati Uniti d'America)
(literal)

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Mancini A.; Borrelli A.; Schiattarella A.; Aloj L.; Aurilio M.; Morelli F.; Pica A.; Occhiello A.; Lorizio R.; Mancini R.; Sica A.; Mazzarella L.; Sica F.; Grieco P.; Novellino E.; Pagnozzi D.; Pucci P. and Rommelaere J. (literal)

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Department of Molecular Biology and Biotherapy, National Cancer Institute ''G. Pascale'' Naples, Naples, Italy Department of Nuclear Medicine, National Cancer Institute ''G. Pascale'' Naples, Naples, Italy Institute of Genetic and Biophysic.-A. Buzzati Traverso Naples, Naples, Italy Department of Biological Science, University Federico II-Naples, Naples, Italy Department of Surgical Veterinary, University Federico II-Naples, Naples, Italy Department of Chemistry, University Federico II-Naples, Naples, Italy Department of Pharmacology and Toxicology, University Federico II-Naples, Naples, Italy Department of Organic Chemistry, University Federico II-Naples, Naples, Italy Deutsches Krebsforschungszentrum, Infection and Cancer Program, Abt.F010 and INSERM U701, Heidelberg, Germany (literal)

Titolo

Biophysical and biochemical characterization of a liposarcoma-derived recombinant MnSOD protein acting as an anticancer agent (literal)

Abstract

A recombinant MnSOD (rMnSOD) synthesized by specific cDNA clones derived from a liposarcoma cell line was shown to have the same sequence as the wild-type MnSOD expressed in the human myeloid leukaemia cell line U937, except for the presence of the leader peptide at the N-terminus. These results were fully confirmed by the molecular mass of rMnSOD as evaluated by ES/MS analysis (26662.7 Da) and the nucleotide sequence of the MnSOD cDNA. The role of the leader peptide in rMnSOD was investigated using a fluorescent and/or 68Gallium-labelled synthetic peptide. The labelled peptide permeated MCF-7 cells and uptake could be inhibited in the presence of an excess of oestrogen. In vivo it was taken up by the tumour, suggesting that the molecule can be used for both therapy and diagnosis. The in vitro and in vivo pharmacology tests confirmed that rMnSOD is only oncotoxic for tumour cells expressing oestrogen receptors. Pharmacokinetic studies in animals performed with 125I- and 131I-labelled proteins confirmed that, when administered systemically, rMnSOD selectively reached the tumour, where its presence was unambiguously demonstrated by scintigraphic and PET scans. PCR analysis revealed that Bax gene expression was increased and the Bcl2 gene was down regulated in MCF7 cells treated with rMnSOD, which suggests that the protein induces a pro-apoptotic mechanism. (literal)

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