Korean J Physiol Pharmacol.
2023 Jul;27(4):383-398. 10.4196/kjpp.2023.27.4.383.
Dihydroaustrasulfone alcohol induces apoptosis in nasopharyngeal cancer cells by inducing reactive oxygen speciesdependent inactivation of the PI3K/AKT pathway
- Affiliations
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- 1Department of Surgery, Tungs’ Taichung Metro Harbor Hospital, Taichung 435, Taiwan
- 2College of Medicine, National Chung Hsing University, Taichung 402, Taiwan
- 3General Education Center, Jenteh Junior College of Medicine, Nursing and Management, Miaoli 356, Taiwan
- 4Hemato-Oncology Division, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan
- 5Institute of Biomedical Science, The iEGG and Animal Biotechnology Center, National ChungHsing University, Taichung 402, Taiwan
- 6Department of Molecular Medicine and Surgery, Karolinska Institute, SE-17177 Stockholm, Sweden
- 7Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 804, Taiwan
- 8National Museum of Marine Biology and Aquarium, Pingtung 944, Taiwan
- 9Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan
- 10Department of Pharmacology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- KMID: 2544140
- DOI: http://doi.org/10.4196/kjpp.2023.27.4.383
Abstract
- Dihydroaustrasulfone alcohol (DA), the synthetic precursor of a natural compound (austrasulfone) isolated from the coral species Cladiella australis, has shown cytotoxic effects against cancer cells. However, it is unknown whether DA has antitumor effects on nasopharyngeal carcinoma (NPC). In this study, we determined the antitumor effects of DA and investigated its mechanism of action on human NPC cells. The MTT assay was used to determine the cytotoxic effect of DA. Subsequently, apoptosis and reactive oxygen species (ROS) analyses were performed by using flow cytometry. Apoptotic and PI3K/AKT pathway-related protein expression was determined using Western blotting. We found that DA significantly reduced the viability of NPC-39 cells and determined that apoptosis was involved in DA-induced cell death. The activity of caspase-9, caspase-8, caspase-3, and PARP induced by DA suggested caspase-mediated apoptosis in DA-treated NPC-39 cells. Apoptosis-associated proteins (DR4, DR5, FAS) in extrinsic pathways were also elevated by DA. The enhanced expression of proapoptotic Bax and decreased expression of antiapoptotic BCL-2 suggested that DA mediated mitochondrial apoptosis. DA reduced the expression of pPI3K and p-AKT in NPC-39 cells. DA also reduced apoptosis after introducing an active AKT cDNA, indicating that DA could block the PI3K/AKT pathway from being activated. DA increased intracellular ROS, but N-acetylcysteine (NAC), a ROS scavenger, reduced DA-induced cytotoxicity. NAC also reversed the chances in pPI3K/AKT expression and reduced DA-induced apoptosis. These findings suggest that ROSmediates DA-induced apoptosis and PI3K/AKT signaling inactivation in human NPC cells.
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