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Oxidative Medicine and Cellular Longevity
Volume 2019, Article ID 6342104, 21 pages
Research Article

BA6 Induces Apoptosis via Stimulation of Reactive Oxygen Species and Inhibition of Oxidative Phosphorylation in Human Lung Cancer Cells

1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan
2School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
3Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
4Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung 80145, Taiwan
5Department of Orthopaedic Surgery, Ping-Tung Christian Hospital, Pingtung 90059, Taiwan
6Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan
7Department of Obstetrics and Gynecology and Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan
8Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
9Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
10Graduate Institute of Marine Biology, National Dong Hwa University, Pingtung 944, Taiwan
11National Museum of Marine Biology and Aquarium, Pingtung 944, Taiwan
12Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
13Center for Neuroscience, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
14Department of Neurosurgery and Surgery, Kaohsiung Armed Forces General Hospital, Kaohsiung 80284, Taiwan
15Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan

Correspondence should be addressed to Nan-Fu Chen; moc.liamg@88660nehc and Hsiao-Mei Kuo; moc.liamg@oukiemoaish

Received 16 September 2018; Revised 11 January 2019; Accepted 30 January 2019; Published 7 May 2019

Academic Editor: Sander Bekeschus

Copyright © 2019 Meng-Hsuan Cheng et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Lung cancer is the leading cause of cancer deaths in the world, with a five-year survival rate of less than 30%. Clinically effective chemotherapeutic treatments at the initial stage may eventually face the dilemma of no drug being effective due to drug resistance; therefore, finding new effective drugs for lung cancer treatment is a necessary and important issue. Compounds capable of further increasing the oxidative stress of cancer cells are considered to have anticancer potential because they possessed the ability to induce apoptosis. This study mainly investigated the effects of BA6 (heteronemin), the marine sponge sesterterpene, on lung cancer cell apoptosis, via modulation of mitochondrial reactive oxygen species (mtROS) and oxidative phosphorylation (OXPHOS). BA6 has cellular cytotoxic activities against a variety of cancer cell lines, but it has no effect on nontumor cells. The BA6-treated lung cancer cells show a significant increase in both cellular ROS and mtROS, which in turn caused the loss of mitochondrial membrane potential (MMP). The increase of oxidative stress in lung cancer cells treated with BA6 was accompanied by a decrease in the expression of antioxidant enzymes Cu/Zn SOD, MnSOD, and catalase. In addition, OXPHOS performed in the mitochondria and glycolysis in the cytoplasm were inhibited, which subsequently reduced downstream ATP production. Pretreatment with mitochondria-targeted antioxidant MitoTEMPO reduced BA6-induced apoptosis through the mitochondria-dependent apoptotic pathway, which was accompanied by increased cell viability, decreased mtROS, enhanced MMP, and suppressed expression of cleaved caspase-3 and caspase-9 proteins. In conclusion, the results of this study clarify the mechanism of BA6-induced apoptosis in lung cancer cells via the mitochondrial apoptotic pathway, suggesting that it is a potentially innovative alternative to the treatment of human lung cancer.