Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Induction of Apoptosis in Arsenic Trioxide-treated Lung Cancer A549 Cells by Buthionine Sulfoximine

  • Han, Yong Hwan (Department of Physiology, Medical School, Institute for Medical Sciences, Center for Healthcare Technology Development, Chonbuk National University) ;
  • Kim, Sung Zoo (Department of Physiology, Medical School, Institute for Medical Sciences, Center for Healthcare Technology Development, Chonbuk National University) ;
  • Kim, Suhn Hee (Department of Physiology, Medical School, Institute for Medical Sciences, Center for Healthcare Technology Development, Chonbuk National University) ;
  • Park, Woo Hyun (Department of Physiology, Medical School, Institute for Medical Sciences, Center for Healthcare Technology Development, Chonbuk National University)
  • Received : 2007.12.20
  • Accepted : 2008.03.17
  • Published : 2008.08.31
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Abstract

Arsenic trioxide (ATO) affects many biological processes such as cell proliferation, apoptosis, differentiation and angiogenesis. L-buthionine sulfoximine (BSO) is an inhibitor of GSH synthesis. We tested whether ATO reduced the viability of lung cancer A549 cells in vitro, and investigated the in vitro effect of the combination of ATO and BSO on cell viability in relation to apoptosis and the cell cycle. ATO caused a dose-dependant decrease of viability of A549 cells with an $IC_{50}$ of more than $50{\mu}m$. Low doses of ATO or BSO ($1{\sim}10{\mu}m$) alone did not induce cell death. However, combined treatment depleted GSH content and induced apoptosis, loss of mitochondrial transmembrane potential (${\Delta}{\Psi}_m$) and cell cycle arrest in G2. Reactive oxygen species (ROS) increased or decreased depending on the concentration of ATO. In addition, BSO generally increased ROS in ATO-treated A549 cells. ROS levels were at least in part related to apoptosis in cells treated with ATO and/or BSO. In conclusion, we have demonstrated that A549 lung cells are very resistant to ATO, and that BSO synergizes with clinically achievable concentration of ATO. Our results suggest that combination treatment with ATO and BSO may be useful for treating lung cancer.

Keywords

Acknowledgement

Supported by : Korean Science and Engineering Foundation

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