Journal article
Mitochondria-targeted nitroxides exacerbate fluvastatin-mediated cytostatic and cytotoxic effects in breast cancer cells
Cancer biology & therapy, Vol.12(8), pp.707-717
10/15/2011
DOI: 10.4161/cbt.12.8.16441
PMCID: PMC3218525
PMID: 21799303
Abstract
Mito-CP
11
, a mitochondria-targeted nitroxide formed by conjugating a triphenylphosphonium cation to a five-membered nitroxide, carboxy-proxyl (CP), has been used as a superoxide dismutase (SOD) mimetic. In this study, we investigated the antiproliferative and cytotoxic properties of submicromolar levels of Mito-CP
11
alone and in combination with fluvastatin, a well known cholesterol lowering drug, in breast cancer cells. Mito-CP
11
, but not CP or CP plus the cationic ligand, methyl triphenylphosphonium (Me-TPP
+
), inhibited MCF-7 breast cancer cell proliferation. Mito-CP
11
had only minimal effect on MCF-10A, non-tumorigenic mammary epithelial cells. Mito-CP
11
, however, significantly enhanced fluvastatin-mediated cytotoxicity in MCF-7 cells. Mito-CP
11
alone and in combination with fluvastatin inhibited nuclear factor kappaB (NFκB) activity mainly in MCF-7 cells. We conclude that mitochondria-targeted nitroxide antioxidant molecules (such as Mito-CP
11
) that are non-toxic to non-tumorigenic cells could enhance the cytostatic and cytotoxic effects of statins in breast cancer cells. This strategy of combining mitochondria-targeted non-toxic molecules with cytotoxic chemotherapeutic drugs may be successfully used to enhance the efficacy of antitumor therapies in breast cancer treatment.
Details
- Title: Subtitle
- Mitochondria-targeted nitroxides exacerbate fluvastatin-mediated cytostatic and cytotoxic effects in breast cancer cells
- Creators
- Gang Cheng - Medical College of WisconsinMarcos Lopez - Medical College of WisconsinJacek Zielonka - Medical College of WisconsinAndrew D Hauser - Medical College of WisconsinJoy Joseph - Medical College of WisconsinDonna McAllister - Medical College of WisconsinJ. Jordi Rowe - Cleveland ClinicSonia L Sugg - University of IowaCarol L Williams - Medical College of WisconsinBalaraman Kalyanaraman - Medical College of Wisconsin
- Resource Type
- Journal article
- Publication Details
- Cancer biology & therapy, Vol.12(8), pp.707-717
- Publisher
- Landes Bioscience
- DOI
- 10.4161/cbt.12.8.16441
- PMID
- 21799303
- PMCID
- PMC3218525
- ISSN
- 1538-4047
- eISSN
- 1555-8576
- Language
- English
- Date published
- 10/15/2011
- Academic Unit
- Surgery
- Record Identifier
- 9984322947802771
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