Abstract
Therapeutic modalities that overcome the antiapoptotic function of Bcl-2 that is often overexpressed in cancer cells are expected to he a novel strategy for cancer treatment. We previously reported that the leukemic cell death induced by an N-terminally truncated Bax (ΔN Bax: corresponding to amino acid 112-192 of full-length Bax) was not blocked by Bcl-2 or Bcl-XL owing to the lack of the BH3 domain needed to interact with the antiapoptotic Bcl-2 family molecules. In this study, we used the Cre-loxP system that allowed us to propagate adenoviruses expressing ΔN Bax, and investigated the effects of the ΔN Bax gene transfer into A549 and NCI-H1299 nonsmall cell lung cancer cell lines. ΔN Bax showed more cell-death-inducing activity in both cells than did the full-length Bax in vitro. It was found that the ΔN Bax-induced cell death was not inhibited by the pancaspase inhibitor z-VAD-fmk, suggesting that ΔN Bax induces cell death through a caspase-independent mechanism. Intratumoral injection of adenoviruses expressing ΔN Bax into A549 tumors in Balh/c nude mice showed a significantly stronger suppression of tumor growth (74%) than full-length Bax (25%) compared to the control. Our results suggest that ΔN Bax may provide a better alternative than currently used cytotoxic genes in cancer gene therapy trials.
Original language | English |
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Pages (from-to) | 2655-2663 |
Number of pages | 9 |
Journal | Oncogene |
Volume | 22 |
Issue number | 17 |
DOIs | |
Publication status | Published - 2003 May 1 |
Externally published | Yes |
Keywords
- Apoptosis
- BAX
- Gene therapy
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research