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Mol. Cells 2008; 26(2): 158-164

Published online August 31, 2008

© The Korean Society for Molecular and Cellular Biology

Induction of Apoptosis in Arsenic Trioxide-treated Lung Cancer A549 Cells by Buthionine Sulfoximine

Yong Hwan Han, Sung Zoo Kim, Suhn Hee Kim and Woo Hyun Park

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 IC50 of more than 50 ?M. Low doses of ATO or BSO (1~10 ?M) alone did not induce cell death. However, combined treatment depleted GSH content and induced apoptosis, loss of mitochondrial transmembrane potential (??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 A549, apoptosis, arsenic trioxide, GSH, L-buthionine sulfoximine, ROS

Article

Research Article

Mol. Cells 2008; 26(2): 158-164

Published online August 31, 2008

Copyright © The Korean Society for Molecular and Cellular Biology.

Induction of Apoptosis in Arsenic Trioxide-treated Lung Cancer A549 Cells by Buthionine Sulfoximine

Yong Hwan Han, Sung Zoo Kim, Suhn Hee Kim and Woo Hyun Park

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 IC50 of more than 50 ?M. Low doses of ATO or BSO (1~10 ?M) alone did not induce cell death. However, combined treatment depleted GSH content and induced apoptosis, loss of mitochondrial transmembrane potential (??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: A549, apoptosis, arsenic trioxide, GSH, L-buthionine sulfoximine, ROS

Mol. Cells
Aug 31, 2022 Vol.45 No.8, pp. 513~602
COVER PICTURE
Cryo-EM structure of human porphyrin transporter ABCB6 (main figure) shows that binding of hemin (inset, magenta) in concert with two glutathione molecules (cyan) primes ABCB6 for high ATP turnover (Kim et al., pp. 575-587).

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