p73β-Expressing recombinant adenovirus: a potential anticancer agent

Das, Sanjeev ; Nama, Srikanth ; Antony, Sini ; Somasundaram, Kumaravel (2005) p73β-Expressing recombinant adenovirus: a potential anticancer agent Cancer Gene Therapy, 12 . pp. 417-426. ISSN 0929-1903

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Official URL: http://www.nature.com/cgt/journal/v12/n4/abs/77008...

Related URL: http://dx.doi.org/10.1038/sj.cgt.7700803


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 p73β (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 p73β levels, which is also functional as it activated the known target gene p21WAF1/CIP1. 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:Article
Source:Copyright of this article belongs to Nature Publishing Group.
Keywords:p73; Adenovirus; Cell Cycle Arrest; Apoptosis; Chemosensitivity
ID Code:49701
Deposited On:20 Jul 2011 13:57
Last Modified:20 Jul 2011 13:57

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