Manganese Superoxide Dismutase Is a Promising Target for Enhancing Chemosensitivity of Basal-like Breast Carcinoma

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Article on manganese superoxide dismutase as a promising target for enhancing chemosensitivity of basal-like breast carcinoma.

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21 p.: ill.

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Kumar, Alan Prem; Loo, Ser Yue; Shin, Sung Won; Tan, Tuan Zea; Eng, Chon Boon; Singh, Rajeev et al. August 21, 2013.

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Article on manganese superoxide dismutase as a promising target for enhancing chemosensitivity of basal-like breast carcinoma.

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21 p.: ill.

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Abstract: 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: The 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.

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  • Antioxidants and Redox Signaling, 2013, New Rochelle: Mary Ann Liebert, Inc.

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  • Publication Title: Antioxidants and Redox Signaling
  • Volume: 20
  • Issue: 15
  • Pages: 21
  • Peer Reviewed: Yes

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  • August 21, 2013

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  • May 29, 2014, 5:29 p.m.

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Kumar, Alan Prem; Loo, Ser Yue; Shin, Sung Won; Tan, Tuan Zea; Eng, Chon Boon; Singh, Rajeev et al. Manganese Superoxide Dismutase Is a Promising Target for Enhancing Chemosensitivity of Basal-like Breast Carcinoma, article, August 21, 2013; [New Rochelle, New York]. (digital.library.unt.edu/ark:/67531/metadc287058/: accessed December 13, 2018), University of North Texas Libraries, Digital Library, digital.library.unt.edu; crediting UNT College of Arts and Sciences.