New target for tumor angiogenesis inhibitors identified
NEW YORK (Reuters Health) - A zipper protein called c-Jun, which has been linked to cell proliferation and apoptosis, may represent a novel target for inhibitors of tumor angiogenesis and growth, according to a report published in the May 5th issue of the Journal of the National Cancer Institute.


Using various in vitro and in vivo methods, Dr. Levon M. Khachigian, from The University of New South Wales in Sydney, Australia, and colleagues found that deoxyribozymes targeting c-Jun inhibited solid tumor growth and angiogenesis.


In cell culture, the c-Jun-targeted doxyribozymes inhibited various endothelial cell activities, including proliferation, migration, chemoinvasion, and tubule formation. In rats, treatment with the deoxyribozymes blocked growth factor-induced corneal neovascularization. Lastly, the deoxyribozymes inhibited tumor growth in a murine model of melanoma.


"Our present findings provide the first direct evidence that c-Jun is a key mediator of angiogenesis and suggest the potential clinical utility of deoxyribozymes specifically targeting this (zipper) protein in pathologies involving angiogenesis," the authors note.


Angiogenesis inhibitors, like those used in the current study, "may target tumor-associated endothelial cells as well as the tumor cells themselves, thus preventing the production of angiogenic activity by tumor cells and inhibiting the endothelial cell response," Dr. Judah Folkman, from the Children's Hospital in Boston, notes in a related editorial. "Therefore, deoxyribozymes targeting c-Jun could act as both direct and indirect inhibitors of angiogenesis."
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