Journal article
Differential Susceptibility of Nonmalignant Human Breast Epithelial Cells and Breast Cancer Cells to Thiol Antioxidant-Induced G1-Delay
Antioxidants & redox signaling, Vol.7(5-6), pp.711-718
05/2005
DOI: 10.1089/ars.2005.7.711
PMID: 15890017
Abstract
Reactive oxygen species (ROS) and ROS signaling have been implicated in a variety of human pathophysiological conditions that involve aberrant cellular proliferation, particularly cancer. We hypothesize that intracellular redox state differentially affects cell-cycle progression in nonmalignant versus malignant cells. The thiol antioxidant, N-acetyl-L-cysteine (NAC), was used to alter intracellular redox state in nonmalignant human breast epithelial (MCF-10A) and breast cancer cells (MCF-7 and MDA-MB-231). Treatment of cells with NAC resulted in significant augmentation of intracellular small-molecular-weight thiols, glutathione and cysteine. In addition, NAC treatment decreased oxidation of a prooxidant-sensitive dye in MCF-10A cells, but not in MDA-MB-231 and MCF-7 cells. NAC-induced shifts in intracellular redox state toward a more reducing environment caused G(1) delays in MCF-10A cells without causing any significant changes in MCF-7 and MDA-MB-231 cell-cycle progression. NAC treatment of MCF-10A (but not MCF-7 and MDA-MB-231) was accompanied by a decrease in cyclin D1 and an increase in p27 protein levels, which correlated with increased retinoblastoma protein hypophosphorylation. These results show differential redox control of progression from G(1) to S in nonmalignant versus malignant cells and support the hypothesis that loss of a redox control of the cell cycle could contribute to aberrant proliferation seen in cancer cells.
Details
- Title: Subtitle
- Differential Susceptibility of Nonmalignant Human Breast Epithelial Cells and Breast Cancer Cells to Thiol Antioxidant-Induced G1-Delay
- Creators
- Sarita G Menon - Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, IAMitchell C Coleman - Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, IASusan A Walsh - Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, IADouglas R Spitz - Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, IAPrabhat C Goswami - Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, IA
- Resource Type
- Journal article
- Publication Details
- Antioxidants & redox signaling, Vol.7(5-6), pp.711-718
- DOI
- 10.1089/ars.2005.7.711
- PMID
- 15890017
- ISSN
- 1523-0864
- eISSN
- 1557-7716
- Language
- English
- Date published
- 05/2005
- Academic Unit
- Radiology; Pathology; Orthopedics and Rehabilitation; Radiation Oncology
- Record Identifier
- 9984040348102771
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