The Korean Journal of Physiology and Pharmacology

  • 제27권4호
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  • Pages.383-398
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  • 2023
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  • 1226-4512(pISSN)
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  • 2093-3827(eISSN)
대한약리학회 (The Korean Society of Pharmacology)
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Dihydroaustrasulfone alcohol induces apoptosis in nasopharyngeal cancer cells by inducing reactive oxygen species-dependent inactivation of the PI3K/AKT pathway

  • Kok-Tong Tan (Department of Surgery, Tungs' Taichung Metro Harbor Hospital) ;
  • Yu-Hung Shih (Hemato-Oncology Division, Department of Internal Medicine, Changhua Christian Hospital) ;
  • Jiny Yin Gong (Institute of Biomedical Science, The iEGG and Animal Biotechnology Center, National ChungHsing University) ;
  • Xiang Zhang (Department of Molecular Medicine and Surgery, Karolinska Institute) ;
  • Chiung-Yao Huang (Department of Marine Biotechnology and Resources, National Sun Yat-sen University) ;
  • Jui-Hsin Su (National Museum of Marine Biology and Aquarium) ;
  • Jyh-Horng Sheu (Department of Marine Biotechnology and Resources, National Sun Yat-sen University) ;
  • Chi-Chen Lin (Institute of Biomedical Science, The iEGG and Animal Biotechnology Center, National ChungHsing University)
  • 투고 : 2023.03.04
  • 심사 : 2023.04.12
  • 발행 : 2023.07.01
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초록

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 ROS-mediates DA-induced apoptosis and PI3K/AKT signaling inactivation in human NPC cells.

키워드

과제정보

This study was financially supported by the iEGG and Animal Biotechnology Center from the Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Taiwan Ministry of Education (#MOE-110-S-0023-E), Changhua Christian Hospital (110-CCH-IRP-107) and the Ministry of Science and Technology of Taiwan (107-2320-B-110-001-MY3).

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