Reactive oxygen species-driven mitochondrial injury induces apoptosis by teroxirone in human non-small cell lung cancer cells

Wang,Jing-Ping; Hsieh,Chang-Heng; Liu,Chun-Yen; Lin,Kai-Han; Wu,Pei-Tsun; Chen,Kwun-Min; Fang,Kang

doi:10.3892/ol.2017.6586

Reactive oxygen species-driven mitochondrial injury induces apoptosis by teroxirone in human non-small cell lung cancer cells

Authors:
- Jing-Ping Wang
- Chang-Heng Hsieh
- Chun-Yen Liu
- Kai-Han Lin
- Pei-Tsun Wu
- Kwun-Min Chen
- Kang Fang
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Affiliations: Department of Life Science, National Taiwan Normal University, Taipei 116, Taiwan, R.O.C., Department of Chemistry, National Taiwan Normal University, Taipei 116, Taiwan, R.O.C.
Published online on: July 15, 2017 https://doi.org/10.3892/ol.2017.6586
Pages: 3503-3509
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Teroxirone as an anticancer agent is used to treat human lung cancer by inducing apoptotic cell death. Previous studies have demonstrated that the status of the tumor suppressor p53 determined the onset of apoptotic cell death in human non-small cell lung cancer cells (NSCLC). In order to further understand the underlying mechanisms of lung cancer, the present study explored the targets of teroxirone. By including antioxidants, the present study analyzed changes in cell proliferation, cell cycle division, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), expression of apoptosis markers and cytochrome c distribution. Subsequent to a 12 h treatment with low concentrations of teroxirone, MMP was suppressed, followed by ROS production and apoptosis in lung cancer cells carrying wild type p53. N-acetylcysteine inhibited apoptotic cell death. The depleted expression of p53, reduction of apoptosis-associated active caspase-3 and poly ADP-ribose polymerase cleavage with resurgence of the pro-survival signal protein kinase B, all demonstrated an antioxidant-mediated reduction of apoptosis by teroxirone. The diminished ROS intensity inhibited the release of mitochondrial cytochrome c and DNA damage. The present study provided evidence that teroxirone treatment induced the ROS-activated intrinsic apoptotic pathway, which led to cell death in human NSCLC cells.

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