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Trichostatin A targets the mitochondrial respiratory chain, increasing mitochondrial reactive oxygen species production to trigger apoptosis in human breast cancer cells.
- Source :
-
PloS one [PLoS One] 2014 Mar 13; Vol. 9 (3), pp. e91610. Date of Electronic Publication: 2014 Mar 13 (Print Publication: 2014). - Publication Year :
- 2014
-
Abstract
- Aim: Histone deacetylase inhibitors (HDACIs)-based therapies have stimulated interest via their anti-tumor activities, including apoptosis induction, cell cycle arrest, cell differentiation, and autophagy. However, the mechanisms of HDACI-associated anti-tumor activity are not yet clearly defined. The aim of this study was to explore the key events of Trichostatin A (TSA), a classic HDACI agent, against breast cancer cells.<br />Methods: The MCF-7, MDA-MB-231 and MCF-10A cell lines were evaluated with colony-forming and cell viability assays. Apoptosis and cell cycle distribution were detected by flow cytometry. Mitochondrial function was measured with biochemical assays, flow cytometry and transmission electron microscopy.<br />Results: TSA inhibited breast cancer cell viability and proliferation, without affecting MCF-10A cell. TSA-induced breast cancer cell apoptosis was initiated by G2-M arrest and depended on mitochondrial reactive oxygen species (ROS) produced subsequent to reduced mitochondrial respiratory chain activity. The enhanced mitochondrial ROS production and apoptosis in cancer cells were markedly attenuated by antioxidants, such as N-acetyl cysteine (NAC), reduced glutathione (GSH) and Vitamin C.<br />Conclusion: The present study demonstrated that TSA-induced cell death by arresting cell cycle in G2-M phase and was dependent on production of mitochondria-derived ROS, which was derived from impaired mitochondrial respiratory chain.
- Subjects :
- Cell Differentiation
Cell Division
Cell Proliferation
Cytochromes c metabolism
Electron Transport
Female
G2 Phase
Histone Deacetylase Inhibitors therapeutic use
Humans
MCF-7 Cells drug effects
Membrane Potential, Mitochondrial
Antineoplastic Agents pharmacology
Apoptosis
Breast Neoplasms pathology
Hydroxamic Acids pharmacology
Mitochondria metabolism
Reactive Oxygen Species metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 9
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 24626188
- Full Text :
- https://doi.org/10.1371/journal.pone.0091610