The adenovirus-mediated linamarase/linamarin suicide system: a potential strategy for the treatment of hepatocellular carcinoma.

Abstract

Suicide gene therapy, also known as gene-directed enzyme prodrug therapy, has the potential to provide a cure for hepatocellular carcinoma (HCC), which is a leading cause of cancer death worldwide. Linamarase from cassava is an enzyme that can hydrolyze the innocuous substrate linamarin into cyanide, which can block the mitochondrial respiratory chain of cells. To investigate whether linamarase and linamarin can be used for HCC treatment, a recombinant adenovirus carrying linamarase cDNA was constructed using the ViraPower Adenoviral Expression System. In vitro cytotoxicity assays indicated that the system has a dramatic inhibitory effect and a strong bystander effect on HCC cell lines. Application of the recombinant adenovirus with linamarin in nude mice bearing HCC xenografts also resulted in significant inhibition of the tumors, while the animals did not show any appreciable toxic effects. Our findings provide the first in vitro and in vivo evidence that this system may provide a potential strategy for HCC treatment.

• Authors: Jun Li, Haimin Li, Liang Zhu, Wenjie Song, Ren Li, Desheng Wang, Kefeng Dou
• Journal: Cancer letters (Cancer Lett) Vol. 289 Issue 2 Pg. 217-27 (Mar 28 2010) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 19733963 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Nitriles
• RNA, Messenger
• cyanogenic beta-glucosidase
• beta-Glucosidase
• linamarin

Topics

• Adenoviridae (genetics)
• Adenoviridae Infections (genetics, therapy, virology)
• Animals
• Blotting, Western
• Bystander Effect
• Carcinoma, Hepatocellular (genetics, therapy, virology)
• Cell Proliferation
• Chromatography, High Pressure Liquid
• Gene Transfer Techniques
• Genes, Transgenic, Suicide
• Genetic Therapy
• Humans
• Liver Neoplasms, Experimental (genetics, therapy, virology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Necrosis
• Nitriles (metabolism)
• Oncolytic Virotherapy
• RNA, Messenger (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays
• beta-Glucosidase (genetics, metabolism)