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Int. J. Mol. Sci. 2015, 16(6), 12601-12615; doi:10.3390/ijms160612601

Specific Colon Cancer Cell Cytotoxicity Induced by Bacteriophage E Gene Expression under Transcriptional Control of Carcinoembryonic Antigen Promoter

1
Department of Health Science, University of Jaén, Jaén 23071, Spain
2
Institute of Biopathology and Regenerative Medicine (IBIMER), Granada 18100, Spain
3
Biosanitary Institute of Granada (ibs.GRANADA), SAS-University of Granada, Granada 18071, Spain
4
Department of Human Anatomy and Embryology, School of Medicine, University of Granada, Granada 18012, Spain
5
Institute of Biotechnology and Department of Genetics, University of Granada, Granada 18071, Spain
*
Author to whom correspondence should be addressed.
Academic Editor: Sabrina Angelini
Received: 23 April 2015 / Revised: 26 May 2015 / Accepted: 26 May 2015 / Published: 4 June 2015
(This article belongs to the Special Issue Pharmacogenetics and Personalized Medicine)
View Full-Text   |   Download PDF [1460 KB, uploaded 4 June 2015]   |  

Abstract

Colorectal cancer is one of the most prevalent cancers in the world. Patients in advanced stages often develop metastases that require chemotherapy and usually show a poor response, have a low survival rate and develop considerable toxicity with adverse symptoms. Gene therapy may act as an adjuvant therapy in attempts to destroy the tumor without affecting normal host tissue. The bacteriophage E gene has demonstrated significant antitumor activity in several cancers, but without any tumor-specific activity. The use of tumor-specific promoters may help to direct the expression of therapeutic genes so they act against specific cancer cells. We used the carcinoembryonic antigen promoter (CEA) to direct E gene expression (pCEA-E) towards colon cancer cells. pCEA-E induced a high cell growth inhibition of human HTC-116 colon adenocarcinoma and mouse MC-38 colon cancer cells in comparison to normal human CCD18co colon cells, which have practically undetectable levels of CEA. In addition, in vivo analyses of mice bearing tumors induced using MC-38 cells showed a significant decrease in tumor volume after pCEA-E treatment and a low level of Ki-67 in relation to untreated tumors. These results suggest that the CEA promoter is an excellent candidate for directing E gene expression specifically toward colon cancer cells. View Full-Text
Keywords: carcinoma embryonic antigen; colorectal cancer; E gene; suicide gene therapy; promoter tissue specific carcinoma embryonic antigen; colorectal cancer; E gene; suicide gene therapy; promoter tissue specific
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Rama, A.R.; Hernandez, R.; Perazzoli, G.; Burgos, M.; Melguizo, C.; Vélez, C.; Prados, J. Specific Colon Cancer Cell Cytotoxicity Induced by Bacteriophage E Gene Expression under Transcriptional Control of Carcinoembryonic Antigen Promoter. Int. J. Mol. Sci. 2015, 16, 12601-12615.

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