Next Article in Journal
Next Article in Special Issue
Previous Article in Journal
Previous Article in Special Issue
Cancers 2010, 2(1), 68-87; doi:10.3390/cancers2010068
Article

Superoxide Enhances the Antitumor Combination of AdMnSOD Plus BCNU in Breast Cancer

1
, 1
, 1
, 1
, 1
, 1
, 1,2,*  and 1
Received: 21 December 2009; in revised form: 9 February 2010 / Accepted: 10 February 2010 / Published: 12 February 2010
(This article belongs to the Special Issue Oxidative Stress and Cancer)
View Full-Text   |   Download PDF [729 KB, uploaded 12 February 2010]   |   Browse Figures
Abstract: Overexpression of manganese superoxide dismutase (MnSOD) can sensitize a variety of cancer cell lines to many anticancer drugs. Recent work has shown that cancer cells can be sensitized to cell killing by raising peroxide levels through increased manganese superoxide dismutase (MnSOD) when combined with inhibition of peroxide removal. Here we utilize the mechanistic property of one such anticancer drug, BCNU, which inhibits glutathione reductase (GR), compromising the glutathione peroxidase system thereby inhibiting peroxide removal. The purpose of this study was to determine if anticancer modalities known to produce superoxide radicals can increase the antitumor effect of MnSOD overexpression when combined with BCNU. To enhance MnSOD, an adenoviral construct containing the cDNA for MnSOD (AdMnSOD) was introduced into human breast cancer cell line, ZR-75-1. AdMnSOD infection alone did not alter cell killing, however when GR was inhibited with either BCNU or siRNA, cytotoxicity increased. Futhermore, when the AdMnSOD + BCNU treatment was combined with agents that enhance steady-state levels of superoxide (TNF-α, antimycin, adriamycin, photosensitizers, and ionizing radiation), both cell cytotoxicity and intracellular peroxide levels increased. These results suggest that the anticancer effect of AdMnSOD combined with BCNU can be enhanced by agents that increase generation of superoxide.
Keywords: MnSOD; BCNU; hydrogen peroxide; superoxide; adenovirus; breast cancer MnSOD; BCNU; hydrogen peroxide; superoxide; adenovirus; breast cancer
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Export to BibTeX |
EndNote


MDPI and ACS Style

Sun, W.G.; Weydert, C.J.; Zhang, Y.; Yu, L.; Liu, J.; Spitz, D.R.; Cullen, J.J.; Oberley, L.W. Superoxide Enhances the Antitumor Combination of AdMnSOD Plus BCNU in Breast Cancer. Cancers 2010, 2, 68-87.

AMA Style

Sun WG, Weydert CJ, Zhang Y, Yu L, Liu J, Spitz DR, Cullen JJ, Oberley LW. Superoxide Enhances the Antitumor Combination of AdMnSOD Plus BCNU in Breast Cancer. Cancers. 2010; 2(1):68-87.

Chicago/Turabian Style

Sun, Wenqing G.; Weydert, Christine J.; Zhang, Yuping; Yu, Lei; Liu, Jingru; Spitz, Douglas R.; Cullen, Joseph J.; Oberley, Larry W. 2010. "Superoxide Enhances the Antitumor Combination of AdMnSOD Plus BCNU in Breast Cancer." Cancers 2, no. 1: 68-87.



Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert