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The Cytotoxic activity of the phage E protein suppress the growth of murine B16 melanomas in vitro and in vivo

Ortiz, Raúl and Prados Salazar, José Carlos and Melguizo, Consolacion and Rama, Ana R. and Segura, Ana and Rodríguez-Serrano, Fernando and Boulaiz, Houria and Hita, Fidel and Martinez-Amat, Antonio and Madeddu, Roberto Beniamino and Ramos, Juan L. and Aranega Jiménez, Antonia (2009) The Cytotoxic activity of the phage E protein suppress the growth of murine B16 melanomas in vitro and in vivo. Journal of Molecular Medicine, Vol. 87 (9), p. 899-911. eISSN 1432-1440. Article.

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DOI: 10.1007/s00109-009-0493-9

Abstract

Novel treatment modalities, including gene therapy, are needed for patients with advanced melanoma. The E gene from the phage ϕX174 encodes a 91-aa protein which lyses Escherichia coli by formation of a transmembrane tunnel structure. To evaluate whether this E gene has a cytotoxic impact on melanoma cells in vitro and in vivo, and could therefore be used as a new therapeutic strategy for this tumor type, we selected the B16-F10 murine melanoma cell line as a model. We used a nonviral gene delivery approach (pcDNA3.1/E plasmid) to study the inhibition of melanoma cells' proliferation in vitro and direct intratumoral injection of pcDNA3.1/E complexed with jetPEI to deliver E cDNA to rapidly growing murine melanomas, and found that the E gene has both a strong antiproliferative effect in B16-F10 cells in vitro and induces an efficient decrease in melanoma tumor volume in vivo (90% in 15 days).
Interestingly, the GFP-E fusion protein expressed in melanoma cells was located in the mitochondria. In vitro and in vivo analysis demonstrated significant functional and morphological mitochondrial alterations accompanied by a significant increase of cytochrome c and active caspase-3 and -9 in transfected cells, which suggests that tumoral cell death is mediated by the mitochondrial apoptotic pathway. These results show that E gene expression in melanoma cells has an extraordinary antitumor effect, which means it may be a new candidate for an effective strategy for melanoma treatment.

Item Type:Article
ID Code:3511
Status:Published
Refereed:Yes
Uncontrolled Keywords:Melanoma, E gene, gene therapy, apoptosis, caspase, mitochondria
Subjects:Area 05 - Scienze biologiche > BIO/17 Istologia
Divisions:001 Università di Sassari > 01 Dipartimenti > Scienze biomediche
Publisher:Springer Berlin / Heidelberg
eISSN:1432-1440
Deposited On:22 Jan 2010 13:11

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