Manganese superoxide dismutase is a promising target for enhancing chemosensitivity of basal-like breast carcinoma
Aims: Although earlier reports highlighted a tumor suppressor role for manganese superoxide dismutase (MnSOD), recent evidence indicates increased expression in a variety of human cancers including aggressive breast carcinoma. In the present article, we hypothesized that MnSOD expression is signific...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Journal Article |
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Mary Ann Liebert, Inc. Publishers
2013
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| Online Access: | http://hdl.handle.net/20.500.11937/7351 |
| _version_ | 1848745344125370368 |
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| author | Prem Kumar, Alan Loo, S. Shin, S. Tan, Tuan zea Eng, C. Singh, R. Putti, T. Ong, C. Salto-Tellez, M. Goh, B. Park, J. Thiery, J. Pervaiz, S. Clement, M. |
| author_facet | Prem Kumar, Alan Loo, S. Shin, S. Tan, Tuan zea Eng, C. Singh, R. Putti, T. Ong, C. Salto-Tellez, M. Goh, B. Park, J. Thiery, J. Pervaiz, S. Clement, M. |
| author_sort | Prem Kumar, Alan |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Aims: Although earlier reports highlighted a tumor suppressor role for manganese superoxide dismutase (MnSOD), recent evidence indicates increased expression in a variety of human cancers including aggressive breast carcinoma. In the present article, we hypothesized that MnSOD expression is significantly amplified in the aggressive breast carcinoma basal subtype, and targeting MnSOD could be an attractive strategy for enhancing chemosensitivity of this highly aggressive breast cancer subtype. Results: Using MDA-MB-231 and BT549 as a model of basal breast cancer cell lines, we show that knockdown of MnSOD decreased the colony-forming ability and sensitized the cells to drug-induced cell death, while drug resistance was associated with increased MnSOD expression. In an attempt to develop a clinically relevant approach to down-regulate MnSOD expression in patients with basal breast carcinoma, we employed activation of the peroxisome proliferator-activated receptor gamma (PPARγ) to repress MnSOD expression; PPARγ activation significantly reduced MnSOD expression, increased chemosensitivity, and inhibited tumor growth. Moreover, as a proof of concept for the clinical use of PPARγ agonists to decrease MnSOD expression, biopsies derived from breast cancer patients who had received synthetic PPARγ ligands as anti-diabetic therapy had significantly reduced MnSOD expression. Finally, we provide evidence to implicate peroxynitrite as the mechanism involved in the increased sensitivity to chemotherapy induced by MnSOD repression. Innovation and Conclusion: These data provide evidence to link increased MnSOD expression with the aggressive basal breast cancer, and underscore the judicious use of PPARγ ligands for specifically down-regulating MnSOD to increase the chemosensitivity of this subtype of breast carcinoma. |
| first_indexed | 2025-11-14T06:15:52Z |
| format | Journal Article |
| id | curtin-20.500.11937-7351 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T06:15:52Z |
| publishDate | 2013 |
| publisher | Mary Ann Liebert, Inc. Publishers |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-73512018-03-29T09:05:40Z Manganese superoxide dismutase is a promising target for enhancing chemosensitivity of basal-like breast carcinoma Prem Kumar, Alan Loo, S. Shin, S. Tan, Tuan zea Eng, C. Singh, R. Putti, T. Ong, C. Salto-Tellez, M. Goh, B. Park, J. Thiery, J. Pervaiz, S. Clement, M. Aims: Although earlier reports highlighted a tumor suppressor role for manganese superoxide dismutase (MnSOD), recent evidence indicates increased expression in a variety of human cancers including aggressive breast carcinoma. In the present article, we hypothesized that MnSOD expression is significantly amplified in the aggressive breast carcinoma basal subtype, and targeting MnSOD could be an attractive strategy for enhancing chemosensitivity of this highly aggressive breast cancer subtype. Results: Using MDA-MB-231 and BT549 as a model of basal breast cancer cell lines, we show that knockdown of MnSOD decreased the colony-forming ability and sensitized the cells to drug-induced cell death, while drug resistance was associated with increased MnSOD expression. In an attempt to develop a clinically relevant approach to down-regulate MnSOD expression in patients with basal breast carcinoma, we employed activation of the peroxisome proliferator-activated receptor gamma (PPARγ) to repress MnSOD expression; PPARγ activation significantly reduced MnSOD expression, increased chemosensitivity, and inhibited tumor growth. Moreover, as a proof of concept for the clinical use of PPARγ agonists to decrease MnSOD expression, biopsies derived from breast cancer patients who had received synthetic PPARγ ligands as anti-diabetic therapy had significantly reduced MnSOD expression. Finally, we provide evidence to implicate peroxynitrite as the mechanism involved in the increased sensitivity to chemotherapy induced by MnSOD repression. Innovation and Conclusion: These data provide evidence to link increased MnSOD expression with the aggressive basal breast cancer, and underscore the judicious use of PPARγ ligands for specifically down-regulating MnSOD to increase the chemosensitivity of this subtype of breast carcinoma. 2013 Journal Article http://hdl.handle.net/20.500.11937/7351 10.1089/ars.2013.5295 Mary Ann Liebert, Inc. Publishers restricted |
| spellingShingle | Prem Kumar, Alan Loo, S. Shin, S. Tan, Tuan zea Eng, C. Singh, R. Putti, T. Ong, C. Salto-Tellez, M. Goh, B. Park, J. Thiery, J. Pervaiz, S. Clement, M. Manganese superoxide dismutase is a promising target for enhancing chemosensitivity of basal-like breast carcinoma |
| title | Manganese superoxide dismutase is a promising target for enhancing chemosensitivity of basal-like breast carcinoma |
| title_full | Manganese superoxide dismutase is a promising target for enhancing chemosensitivity of basal-like breast carcinoma |
| title_fullStr | Manganese superoxide dismutase is a promising target for enhancing chemosensitivity of basal-like breast carcinoma |
| title_full_unstemmed | Manganese superoxide dismutase is a promising target for enhancing chemosensitivity of basal-like breast carcinoma |
| title_short | Manganese superoxide dismutase is a promising target for enhancing chemosensitivity of basal-like breast carcinoma |
| title_sort | manganese superoxide dismutase is a promising target for enhancing chemosensitivity of basal-like breast carcinoma |
| url | http://hdl.handle.net/20.500.11937/7351 |