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p73 $\beta$-expressing recombinant adenovirus: a potential anticancer agent

Das, Sanjeev and Nama, Srikanth and Antony, Sini and Somasundaram, Kumaravel (2005) p73 $\beta$-expressing recombinant adenovirus: a potential anticancer agent. In: Cancer Gene Therapy, 12 (4). pp. 417-426.

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Abstract

Tumor suppressor p53-based gene therapy strategy is ineffective in certain conditions. p73, a p53 homologue, could be a potential alternative gene therapy agent as it has been found to be an important determinant of chemosensitivity in cancer cells. Previously, we have reported the generation of a replication-deficient adenovirus expressing p73 $\beta$ (Ad-p73). In this study, we evaluated the therapeutic potential of Ad-p73 against a panel of cancer cells (n=12) of different tissue origin. Ad-p73 infected all the cell lines tested very efficiently resulting in several-fold increase in p73 $\beta$ levels, which is also functional as it activated the known target gene $p21^W^A^F^1^/^C^I^P^1$. Infection with Ad-p73 resulted in potent cytotoxicity in all the cell lines tested. The mechanism of p73-induced cytotoxicity in these cell lines is found to be due to a combination of cell cycle arrest and induction of apoptosis. In addition, exogenous overexpression of p73 by Ad-p73 infection increased the chemosensitivity of cancer cells by many fold to commonly used drug adriamycin. Moreover, Ad-p73 is more efficient than Ad-p53 in enhancing the chemosensitivity of mutant p53 harboring cells. Furthermore, Ad-p73 infection did not induce apoptosis in human normal lung fibroblasts (HEL 299) and human immortalized keratinocytes (HaCaT). These results suggest that Ad-p73 is a potent cytotoxic agent specifically against cancer cells and could be developed as a cancer gene therapy agent either alone or in combination with chemotherapeutic agents.

Item Type: Journal Article
Additional Information: The Copyright belongs to Nature Publishing Group.
Keywords: p73;adenovirus;cell cycle arrest;apoptosis;chemosensitivity
Department/Centre: Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited: 02 Mar 2006
Last Modified: 27 Aug 2008 11:47
URI: http://eprints.iisc.ernet.in/id/eprint/5667

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