Enhancing the antitumor activity of adriamycin and ionizing radiation

Wenqing Sun; Amanda L Kalen; Brian J Smith; Joseph J Cullen; Larry W Oberley

doi:10.1158/0008-5472.CAN-09-0396

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Enhancing the antitumor activity of adriamycin and ionizing radiation

Journal article

Open access

Peer reviewed

Enhancing the antitumor activity of adriamycin and ionizing radiation

Wenqing Sun, Amanda L Kalen, Brian J Smith, Joseph J Cullen and Larry W Oberley

Cancer research (Chicago, Ill.), Vol.69(10), pp.4294-4300

05/15/2009

DOI: 10.1158/0008-5472.CAN-09-0396

PMCID: PMC2688464

PMID: 19401447

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https://doi.org/10.1158/0008-5472.CAN-09-0396View

Published (Version of record) Open Access

Abstract

Overexpression of manganese superoxide dismutase (MnSOD), when combined with certain chemicals that inhibit peroxide removal, increases cancer cell cytotoxicity. Elevating MnSOD levels in cells enhances the conversion of superoxide (O(2)(*-)) to hydrogen peroxide (H(2)O(2)), combined with inhibiting the removal of H(2)O(2), further increases H(2)O(2) levels, leading to increased cytotoxicity. We hypothesized that increasing endogenous O(2)(*-) production in cells that were pretreated with adenoviral MnSOD (AdMnSOD) plus 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) would lead to an increased level of intracellular H(2)O(2) accumulation and increased cell killing. The cytotoxic effects of Adriamycin or radiation, agents known to produce O(2)(*-), were determined in MDA-MB-231 breast cancer cells pretreated with AdMnSOD plus BCNU both in vitro and in vivo. In vitro, AdMnSOD plus BCNU sensitized cells to the cytotoxicity of Adriamycin or radiation. In vivo, AdMnSOD, BCNU, and Adriamycin or ionizing radiation inhibited tumor growth and prolonged survival. The results suggest that agents that produce O(2)(*-) in combination with AdMnSOD plus BCNU may represent a powerful new antitumor regimen against breast cancer.

Cell Survival - drug effects

Doxorubicin - therapeutic use

Superoxide Dismutase - genetics

Glutathione - metabolism

Humans

Antineoplastic Agents - therapeutic use

Combined Modality Therapy

Glutathione Disulfide - metabolism

Breast Neoplasms - drug therapy

Cell Survival - radiation effects

Hydrogen Peroxide - metabolism

Carmustine - therapeutic use

Breast Neoplasms - genetics

Superoxides - metabolism

Cell Line, Tumor

Female

Superoxide Dismutase - metabolism

Radiation, Ionizing

Details

Title: Subtitle: Enhancing the antitumor activity of adriamycin and ionizing radiation
Creators: Wenqing Sun - Free Radical and Radiation Biology Program, Department of Radiation Oncology, and Holden Comprehensive Cancer Center, Carver College of Medicine, The University of Iowa, and VA Medical Center, Iowa City, IA 52242, USA
Amanda L Kalen
Brian J Smith
Joseph J Cullen
Larry W Oberley
Resource Type: Journal article
Publication Details: Cancer research (Chicago, Ill.), Vol.69(10), pp.4294-4300
Publisher: United States
DOI: 10.1158/0008-5472.CAN-09-0396
PMID: 19401447
PMCID: PMC2688464
ISSN: 0008-5472
eISSN: 1538-7445
Grant note: P01 CA066081-09 / NCI NIH HHS CA 66081 / NCI NIH HHS P01 CA066081-060005 / NCI NIH HHS P01 CA066081 / NCI NIH HHS I01 BX001318 / BLRD VA
Language: English
Date published: 05/15/2009
Academic Unit: Biostatistics; Surgery; Radiation Oncology; Holden Comprehensive Cancer Center
Record Identifier: 9983997473202771

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